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Cardiorespiratory responses of healthy middle-aged men to steady-state positive and negative work performed… Chung, Frank 1989

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CARDIORESPIRATORY RESPONSES OF HEALTHY MIDDLE-AGED MEN TO STEADY-STATE POSITIVE AND NEGATIVE WORK PERFORMED ON A CYCLE ERGOMETER By FRANK CHUNG B.Sc.(P.T.) McGill University, 1981 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE I n THE FACULTY OF GRADUATE STUDIES INTERDISCIPLINARY STUDIES (Department of Medicine, School of Rehabilitation Medicine, School of Physical Education and Recreation) We accept t h i s t h e s i s as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA August 1989 (c) Frank Chung, 1989 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of The University of British Columbia Vancouver, Canada DE-6 (2/88) ABSTRACT The p h y s i o l o g i c a l responses of negative work involving predominantly e c c e n t r i c muscle contraction were compared to p o s i t i v e work invo l v i n g predominantly concentric muscle contraction i n twelve older healthy subjects between 39 and G5 years of age. A motorized cycle ergometer was used f o r steady state exercise t e s t i n g . To study the p h y s i o l o g i c a l response to p o s i t i v e and negative work, pedalling frequencies of 35, 55, and 75 rpm and a constant power output of 60 Watts were chosen. Steady state values of oxygen consumption (V02), heart rate (HR), minute v e n t i l a t i o n (VE), t i d a l volume <VT) and breathing frequency (fb) were obtained during s i x t e s t conditions, namely, p o s i t i v e and negative work at each of the three pedalling frequencies. A l l p h y s i o l o g i c a l measures were greater during p o s i t i v e work than negative work (p<0.001) except f o r fb (p>0.05). The greater V02 (1.14+.0.13 and 0.62+0.IS 1/min (mean+standard deviation) during p o s i t i v e and negative work re s p e c t i v e l y ) , HR (95. 8+.10. 7 and 81.8 + 13.6 bpm) and VE (26.7+5.5 and 16.5+5.2 1/min) during p o s i t i v e work were consistent with the greater energy e f f i c i e n c y of negative work. The greater VE during p o s i t i v e work r e f l e c t e d a greater VT (1.46+.32 1/br) than negative work (0.99+.31 1/br) while fb was the same (18.7+.4.0 and 17.5+5.6 br/min) f o r both p o s i t i v e and negative work. During p o s i t i v e work, a l l p h y s i o l g i c a l v a r i a b l e s were greatest at 75 compared to 35 and 55 rpm (p<0.05) except f o r fb which showed no s i g n i f i c a n t d i f f e r e n c e i i across the three p e d a l l i n g frequencies <p>0.05). During negative work, V02 and HR were greatest at 75 and 35 rpm compared to 55 rpm <p<0.05), and VE and VT were greater at 75 than at 55 rpm (p<0.05), whereas fb was not d i f f e r e n t among pedalling frequencies (p>0.05). The slopes and in t e r c e p t s of the regression l i n e s r e l a t i n g HR and V02, VE and V02, VT and VE, and fb and VE were i d e n t i c a l between p o s i t i v e and negative work except f o r a higher intercept f o r the VE and V02 r e l a t i o n s h i p during negative work. Thus, i t was concluded that at a power output of 60 Watts, p h y s i o l o g i c a l responses such as V02, HR and VE during p o s i t i v e and negative work were q u a l i t a t i v e l y s i m i l a r . When changes i n VT and fb were compared from baseline to steady-state f o r p o s i t i v e work, however, VT and fb both increased. In contrast, f o r negative work, VT increased minimally while r e l a t i v e l y greater increases i n fb were observed f o r peda l l i n g frequencies of 35 and 55 rpm. The r e l a t i v e l y greater e f f e c t of negative work on fb compared with p o s i t i v e work i s not predicted from the known v e n t i l a t o r y responses to low i n t e n s i t y exercise. Further study i s needed to e l u c i d a t e the precise mechanism f o r t h i s predominant increase i n fb during negative work. TABLE OF CONTENTS Page ABSTRACT i i LIST OF TABLES v i LIST OF FIGURES v i i ACKNOWLEDGEMENT v i i i INTRODUCTION I General Purpose 1 II P h y s i o l o g i c a l Responses to Negative Work 3 III E f f e c t of Speed and Power Output on 11 Energy Consumption and E f f i c i e n c y IV E f f e c t of Aging on Acute Exercise 17 Responses V Rationale f o r Study 21 VI Thesis Questions 24 METHODS I Research Design 28 II Subjects 28 III Equipment and Measures 29 IV General Procedures 33 V Data Analysis 38 RESULTS I Subject C h a r a c t e r i s t i c s 41 II Oxygen Consumption 41 III Heart Rate 42 IV Minute V e n t i l a t i o n 43 V T i d a l Volume 45 VI Breathing Frequency 46 iv DISCUSSION I E f f e c t s of Steady State Cycling on 72 Oxygen Consumption II E f f e c t s of Steady State Cycling on Heart 76 Rate III E f f e c t s of Steady State Cycling on Minute 77 V e n t i l a t i o n and i t s Components IV E f f e c t s of Steady State Cycling on Minute 81 V e n t i l a t i o n and i t s Components: Changes from Baseline to Steady State Exercise V Exercise Responses of Older Subjects to 82 Steady State Cycling VI Limitations of the Study 84 CONCLUSIONS 88 BIBLIOGRAPHY 91 APPENDICES Appendix A D e f i n i t i o n s and Comparisons of the 103 Cal c u l a t i o n of Exercise E f f i c i e n c y Appendix B Contribution of Internal Work to Total 106 Work Performed Appendix C Borg's Scales of Subjective Perceived 108 Exertion and Breathlessness during P o s i t i v e and Negative Work with Special Reference to Patients with Cardiorespiratory Disease Appendix D The Exercise Responses of Two Patients 111 with I n t e r s t i t i a l Lung Disease to P o s i t i v e and Negative Work Performed on a Cycle Ergometer. A Case Report. V L I S T O F T A B L E S I Anthropometric and Pulmonary Function Data 48 II Oxygen Consumption during P o s i t i v e and Negative 51 Work at Three Pedalling Frequencies. Univariate and M u l t i v a r i a t e Repeated Measures Analysis. III Heart Rate during P o s i t i v e and Negative Work 54 at Three Pedalling Frequencies. Univariate and M u l t i v a r i a t e Repeated Measures Analysis. IV Minute V e n t i l a t i o n during P o s i t i v e and Negative 59 Work at Three Pedalling Frequencies. Univariate and M u l t i v a r i a t e Repeated Measures Analysis. V T i d a l Volume during P o s i t i v e and Negative 64 Work at Three Pedalling Frequencies. Univariate and M u l t i v a r i a t e Repeated Measures Analysis. VI Breathing Frequency during P o s i t i v e and Negative 69 Work at Three Pedalling Frequencies. Univariate and M u l t i v a r i a t e Repeated Measures Analysis. vi LIST OF FIGURES Fig.1 Force and Ve l o c i t y Relationship 26 Fig.2 Assembly of the Cycle Ergometer 39 Fig.3 Flow Diagram of the Test Protocol 40 Fig.4 Descriptive S t a t i s t i c s f o r Oxygen 49 Consumption Fig.5 Descriptive S t a t i s t i c s f o r Heart Rate 52 Fig.6 Scatter Plot of Heart Rate and Oxygen 55 Consumption Relationship Fig.7 Descriptive S t a t i s t i c s f o r Minute V e n t i l a t i o n 57 Fig.8 Scatter Plot of Minute V e n t i l a t i o n and Oxygen 60 Consumption Relationship Fig.9 Descriptive S t a t i s t i c s f o r T i d a l Volume 62 Fig.10 Scatter Plot of T i d a l Volume and Minute 65 V e n t i l a t i o n Relationship Fig.11 Descriptive S t a t i s t i c s f o r Breathing 67 Frequency Fig.12 Scatter P l o t of Breathing Frequency and 70 Minute V e n t i l a t i o n Relationship v i i ACKNOWLEDGEMENT I would l i k e to acknowledge the guidance of my committee Dr. E Dean, Dr. K. Coutts and Dr. R. L. Pardy. My graduate work would not have been possible without the invaluable assistance of Dr. E. Dean. I would also l i k e to thank Dr. P.K. Chiu, Ms. D. Glover, Dr. K. Gottschling and Dr. D. Reid for t h e i r encouragement. F i n a l l y , I would l i k e to thank a l l my subjects and supportive personnels f o r t h e i r involvement in t h i s study. v i i i INTRODUCTION I G E N E R A L P U R P O S E The unique physiologic properties of negative work have been of considerable i n t e r e s t since 1952 when Abbott and his colleagues connected two b i c y c l e s back-to-back supported on a frame and demonstrated that negative work (eccentric muscle contraction) required l e s s t o t a l energy than p o s i t i v e work (concentric muscle contraction). In that study, the normal forward p e d a l l i n g by one c y c l i s t ( p o s i t i v e work) was r e s i s t e d by the second c y c l i s t who attempted to pedal forwards although the legs were forced backwards (negative work). A dramatic example of the e f f i c i e n c y of negative work was reported by H i l l i n 1954. He had a small woman r e s i s t the forward pedalling of a large a t h l e t i c man. The woman performing negative work r e s i s t e d the a t h l e t i c man with ease supporting the f i n d i n g that torque production during e c c e n t r i c muscle contraction requires s i g n i f i c a n t l y l e s s t o t a l energy than p o s i t i v e work. This observation has been confirmed f o r other forms of negative work including going downstairs [Benedict and Parmenter, 1928 3 , climbing down a la d d e r m i l l CKamon, 1970S, and lowering a weight CSeliger et a l , 19683. The general purpose of t h i s study was to extend our present understanding of the e f f e c t s of negative work on the exercise responses of healthy persons, and i n p a r t i c u l a r 1 middle-aged men. S p e c i f i c a l l y , we hoped to further our understanding of the v e n t i l a t o r y responses to negative work, performed with the legs, on a c y c l e ergometer. This work extended previous studies i n our laboratory on the v e n t i l a t o r y responses during negative work i n the form of downhill walking. In addition to an i n t e r e s t i n the energy-efficiency of negative work, we were inter e s t e d i n the optimization of energy cost as a function of p e d a l l i n g frequency. The existence of an optimal walking and pedalling frequency f o r i n d i v i d u a l s i s well known CSeabury et a l , 19773. However, the e f f e c t of pedalling frequency during negative work performed at a constant work rate has not been well studied. In the present study, peda l l i n g frequencies of 35, 55, and 75 rpm were chosen to examine the e f f e c t s of speed on oxygen consumption and heart rate at a constant work rate of 60 Watts during both p o s i t i v e and negative work. In addition, the e f f e c t of pedalling frequency during p o s i t i v e and negative work on the components of minute v e n t i l a t i o n , namely t i d a l volume and breathing frequency were studied. These preliminary studies were designed to ultimately evaluate the p o t e n t i a l therapeutic r o l e of negative work i n the management of p h y s i c a l l y disabled i n d i v i d u a l s . We purposefully studied middle-aged men who would be more representative of our future patient population. Moreover, the response of middle-aged men to negative work has not been 2 previously reported i n the l i t e r a t u r e . In summary, we investigated the v e n t i l a t o r y responses and energy cost of middle-aged men during p o s i t i v e and negative work using a cyc l e ergometer. In addition, the e f f e c t s of pedalling frequency (speed) at a constant work rate on v e n t i l a t o r y responses and energy cost were also examined. El u c i d a t i o n of the e f f e c t s of negative work on the exercise responses of healthy middle-aged men w i l l provide the basis for future studies with p h y s i c a l l y disabled i n d i v i d u a l s as well as further our knowledge with respect to negative work i n general. II PHYSIOLOGICAL RESPONSES TO NEGATIVE WORK Negative work i s characterized by ecc e n t r i c muscle contraction and p o s i t i v e work i s characterized by concentric muscle contraction. Knuttgen et a l [1971a3 reported that when a muscle developed tension c o n c e n t r i c a l l y , a portion of the energy i s conserved as p o t e n t i a l energy. The conserved energy and work i s equal to the product of the weight of the subject l i f t e d and i t s v e r t i c a l displacement. In contrast, i n ecc e n t r i c muscle contraction, the p o t e n t i a l energy i s passed on to the muscle during lengthening. In concentric contraction, t o t a l heat production equals metabolic heat minus work performed. During e c c e n t r i c contraction, work i s being performed on or absorbed by the muscle. Knuttgen et a l C1971b] further stated that t o t a l heat production i n negative work i s 3 equal to the sum of mechanical work and metabolic heat. Hence, during e c c e n t r i c muscle contraction, work i s enhanced and metabolic energy requirement i s reduced. During e c c e n t r i c muscle contraction, part of the force generated comes from the st r e t c h i n g of the s e r i e s e l a s t i c component u t i l i z i n g the k i n e t i c energy imparted from the s t r e t c h or g r a v i t a t i o n a l force CMoritani et a l , 19883. Stretching p r i o r to concentric muscle contraction, or stretch-shortening cycle, also increases the mechanical e f f i c i e n c y , peak force and power output of subsequent muscle work CAstrand and Rodahl, 1986; Bosco and Komi, 1979; Bosco et a l , 1982; Bosco et a l , 1987; Chapman, 1985; Thomson and Chapman, 1988 3. Ch a r a c t e r i B t i c s of Negative Work Negative work has several p h y s i o l o g i c a l l y d i s t i n c t c h a r a c t e r i s t i c s CKnuttgen, 1986 3. F i r s t , when the same v e l o c i t i e s of concentric and e c c e n t r i c muscle contractions are compared, greater force can be produced i n e c c e n t r i c than other forms of muscle contraction [Asmussen, 1953; Eloranta and Komi, 1980; Komi and Buskirk, 19723. In e c c e n t r i c contraction where muscle i s stretched, i n d i v i d u a l cross bridges develop greater resistance when stretched, consequently greater t o t a l force i s generated than i n concentric contraction [White, 1977 3. The molecular mechanism of e c c e n t r i c muscle contraction, however, i s not f u l l y understood. Goldspink C19773 proposed that when the cross bridges are stretched during e c c e n t r i c muscle 4 contraction, the cross bridges are disengaged from t h e i r o r i g i n a l a c t i v e s i t e before complete c y c l i n g . In t h i s way the cross bridges can g l i d e across a couple of s i t e s without having to depend on ATP to provide energy. Energy may therefore be conserved through t h i s mechanism. Goldspink C1977 3 also reported considerable compliance e x i s t s at the cross bridge l e v e l . Therefore parts of the cross bridge, i n p a r t i c u l a r the S2 fragment, act l i k e a spring. The s p r i n g - l i k e cross bridge w i l l then produce extra tension when stretched. In terms of muscle mechanics, the s t r e t c h i n g of the s e r i e s e l a s t i c component which i s located at the cross bridges of the c o n t r a c t i l e protein CAstrand and Rodahl, 1986; Kirchberger and Schwartz, 1985; Huxley and Simmons, 19713 i s responsible f o r the greater force generated. Fig. 1 shows the c l a s s i c f orce and v e l o c i t y r e l a t i o n s h i p f o r both muscle shortening and lengthening contractions. Lengthening contractions produce greater force than shortening contractions at any muscle contraction v e l o c i t y . A second d i s t i n c t c h a r a c t e r i s t i c i s that integrated electromyographic (IEHG) a c t i v i t y i s lower i n eccentric than concentric muscle contractions CAsmussen, 1953; Asmussen, 1956; Bigland-Ritchie and Woods, 1976; Komi and Buskirk, 1972, Moritani et a l , 1988 3. In addition, IEMG a c t i v i t y has been observed to increase with increasing knee angular v e l o c i t y or mechanical work i n p o s i t i v e work. But i n negative work, IEHG has been reported to remain at very low l e v e l s over a range of 5 power outputs [Komi et a l 1987]. The slope of the regression l i n e r e l a t i n g IEMG and force was l e s s steep i n negative compared with p o s i t i v e work [Bigland-Ritchie and Woods, 1976; Eloranta and Komi, 1980; Komi and Buskirk, 19723. The EMG spike amplitude was also lower i n motor units activated during e c c e n t r i c muscle contraction [Moritani et a l , 19883. This evidence supported the notion that production of a given force required l e s s motor unit a c t i v a t i o n i n e c c e n t r i c compared with concentric muscle contraction [Knuttgen, 1986; Komi et a l , 1987; Moritani et a l , 19883. A t h i r d d i s t i n c t c h a r a c t e r i s t i c of negative work i s i t s lower energy requirement compared to p o s i t i v e work f o r the same power output (work/time) [Abbott and Bigland, 1953; Abbott et a l , 1952; Asmussen, 1953; Klausen and Knuttgen, 1971; Knuttgen et a l , 1971a; Knuttgen et a l , 1971b3. Other i n v e s t i g a t o r s have shown various r e l a t e d physiologic responses are also r e l a t i v e l y lower f o r negative work, f o r example, heart rate, cardiac output, pulmonary v e n t i l a t i o n , r e s p i r a t o r y exchange r a t i o , muscle blood flow and muscle temperature [Abbott et a l , 1952; Asmussen, 1953; Davies and Barnes, 1972b; Knuttgen,1986; Knuttgen et al,1971a; Knuttgen et a l 1971b; Nielsen et a l , 19723. At comparable oxygen consumption, the t o t a l heat production i n negative work i s higher and the skin blood flow needed f o r maintenance of thermal equilibrium i s higher than 6 p o s i t i v e work [Nielsen et a l , 19723. To achieve comparable oxygen consumption, the work rate of negative work could be as high as f i v e times that of p o s i t i v e work [Nielson et a l , 19723. Heart rate has been reported to be higher i n negative work compared to that i n p o s i t i v e work [Nielsen et a l , 1972; Thomson, 1971; Knuttgen et a l , 1971b3. Heart rate increases l i n e a r l y with oxygen consumption i n negative work, however, the rate of increase i s greater i n negative work [Hesser et a l , 19773. Davies and Barnes [1972b3 reported that at comparable oxygen consumption, the cardiac output and heart rate were higher and stroke volume was unchanged i n negative work compared to p o s i t i v e work. With prolonged negative work, the i n v e s t i g a t o r s found that cardiac output was s i m i l a r to p o s i t i v e work over the same time i n t e r v a l but heart rate was higher and stroke volume decreased by 18JC. Others [Nielson et a l , 1972; Thomson, 19713 have reported that cardiac output was the same i n p o s i t i v e and negative work at the same oxygen consumption l e v e l i n d i c a t i n g stroke volume was lower i n negative than i n p o s i t i v e work. Similar observations of unaltered cardiac output, increased skin blood flow, increased heart rate and decreased stroke volume have been made i n subjects working i n a hot compared to a cool environment [William et a l , 1962 3. Minute v e n t i l a t i o n i s reported to be s i m i l a r or elevated during negative work compared with p o s i t i v e work at comparable oxygen consumption when performed on a t r e a d m i l l or c y c l e ergometer [Dean and Ross, 1969; Hesser et a l , 1977; Knuttgen et 7 a l , 1971a; Knuttgen et a l , 1971b; Thomson, 19713. The e f f e c t s of negative vork on the components of minute v e n t i l a t i o n (VE) s p e c i f i c a l l y t i d a l volume (VT) and breathing frequency (fb), however, have not been documented. One exception i s the work of Dean and Ross [1989 3 who reported rapid shallow breathing in healthy subjects during downhill walking at 3.5 mph with a -7% grade on a t r e a d m i l l . Of p a r t i c u l a r i n t e r e s t , two subjects i n t h i s study had t i d a l volumes as low as 0.25 1 and breathing frequencies greater than 70 br/min at t h i s work load. Dean and Ross C19893 speculated that i t was u n l i k e l y t h i s v e n t i l a t o r y response was an adaptive physiologic response per se but rather i t r e f l e c t e d postural and abdominal wall adjustments to walking downhill even at low grades. The net mechanical e f f i c i e n c y c a l c u l a t e d f o r p o s i t i v e work has been reported to range between 19JC-275J [Aura and Komi, 19863. In negative work mechanical e f f i c i e n c y i s d i r e c t l y r e l a t e d to mechanical work or movement v e l o c i t y . Thus unlike p o s i t i v e work, e f f i c i e n c y can be i n excess of 100% i n negative work [Komi et a l , 1987 3. This improved e f f i c i e n c y as proposed by Aura and Komi [1986 3 has to do with greater muscle s t i f f n e s s i n e c c e n t r i c muscle contraction at increasing work rates. The i n v e s t i g a t o r s proposed that e c c e n t r i c muscle contraction required lower oxygen consumption due to the increased s t i f f n e s s phenomenon. A fourth d i s t i n c t c h a r a c t e r i s t i c of negative work i s 8 that when i t i s performed at high i n t e n s i t y and f o r a prolonged period, u l t r a s t r u c t u r a l damage may r e s u l t with severe delayed onset muscle soreness CClarkson and Tremblay, 1988; Newham, 1988; Newham et a l , 1988]. These two phenomena are probably d i r e c t l y related. However the exact mechanism f o r delayed-onset muscle soreness i s s t i l l not understood [Armstrong, 1985; Newham, 1988J. Disturbances are observed i n the c r o s s - s t r i a t e d band pattern and as disorganized m y o f i b r i l l a r material. The les i o n s are mostly l o c a l i z e d i n the Z-band which undergoes streaming, broadening, and often, t o t a l disruption. Z-lines have been reported to disappear completely [Asmussen, 1956; Friden et a l , 1981; Friden et a l 1983] In addition, plasma creatine kinase, i n t e r l e u k i n - i and urinary 3-methylhistidine / cr e a t i n i n e i n untrained subjects were observed to increase s i g n i f i c a n t l y a f t e r negative but not p o s i t i v e work. Negative work invo l v i n g the legs also caused s i g n i f i c a n t intramuscular pressure elevation i n the anterior compartment of the lower leg, which was not seen following p o s i t i v e work. This may be one of the fa c t o r s associated with the development of delayed muscle soreness [Friden et a l , 1986]. Sargeant and Dolan [1987] observed that a bout of negative work performed by the knee extensor muscles resulted i n a s i g n i f i c a n t decrease i n maximum voluntary isometric contraction, short term anaerobic power output, and knee extension force generated at a low frequency (20 Hz) r e l a t i v e to a higher frequency (50 Hz) percutaneous stimulation of the quadriceps muscle. Newham et a l [1988] reported a greater drop i n strength and increase i n 9 pain during e c c e n t r i c muscle contraction when the muscle contracts from a stretched p o s i t i o n . However, i n d i v i d u a l s previously exposed to negative work may adapt such that the muscles become more r e s i s t a n t to damage [Clarkson and Tremblay, 1988; Evans et a l , 1986; Sargeant et a l , 1987]. The f i f t h i n t e r e s t i n g phenomenon associated with negative work i s a progressive upward d r i f t of oxygen consumption which occurs during prolonged moderate to high i n t e n s i t y steady-rate work. This d r i f t of oxygen consumption has been reported to range from 2534-4054 i n various types of negative work [Klausen and Knuttgen, 1971; Davies and Barnes, 1972b; Burke et a l , 19853. Dick and Cavanagh C1987 3 reported a 10% increase i n oxygen consumption and 23% increase in IEMG between minutes 10 and 40 during downhill running. They hypothesized that an upward d r i f t i n oxygen uptake and increasing IEMG during downhill running r e f l e c t e d increased motor unit recruitment within the e c c e n t r i c l y contracting muscles. These e f f e c t s were a t t r i b u t e d to a combination of muscle damage, connective t i s s u e damage, and l o c a l muscle fatigue. In summary, at a comparable power output negative work i s associated with a lower IEMG a c t i v i t y , oxygen uptake, and r e l a t e d p h y s i o l o g i c a l responses compared with p o s i t i v e work. At comparable oxygen consumption, the v e n t i l a t o r y response i s reported to be rapid and shallow during negative work. Other 10 p h y s i o l o g i c a l responses to negative work are s i m i l a r to those observed during p o s i t i v e work performed i n a warm environment. An upward d r i f t i n oxygen consumption has been associated with submaximal negative work whereas t h i s d r i f t i s l e s s pronounced during p o s i t i v e work. Also, high i n t e n s i t y submaximal negative work can be associated with muscle damage and delayed-onset muscle soreness, but these e f f e c t s are l e s s marked i n trained subjects. I l l EFFECT OF SPEED AND POWER OUTPUT ON ENERGY CONSUMPTION AND EFFICIENCY With respect to power output, muscle p h y s i o l o g i s t s have known since H i l l ' s early studies C19383 that the force a muscle can generate and the v e l o c i t y at which the muscle shortens are interdependent. Optimal power or the optimal rate of doing work can be defined by a d i s c r e t e point on the f o r c e - v e l o c i t y curve f o r any muscle. Metabolic studies have shown an in t e r e s t i n g r e l a t i o n s h i p between exercise speed, load and oxygen demand. Abbott and Aubert [19523, f o r example, have shown that during c y c l i n g on an ergometer, a subject's energy cost was not d i r e c t l y r e l a t e d to absolute work load. Rather, a very low pedalling rate was more demanding i n terms of energy cost than an intermediate rate or even higher rate. Benedict and Parmenter [1928 3 showed that i n healthy young women the optimal rate of walking was about 65 meters per minute and that sauntering (34 meters per minute) was uneconomical with respect 11 to energy cost. In fact, f a s t walking rates of 89 meters per minute were more economical with respect to energy cost than the slow sauntering rate. Similar f i n d i n g s were also reported by Banister and Jackson [1967]. In the more recent l i t e r a t u r e on e f f i c i e n c y of p o s i t i v e work, contradictory f i n d i n g s are noted [Aura and Komi, 1986; McCann and Gliner, 1982; Suzuki, 1979]. Suzuki [1979] reported when pedalling frequency was increased from 60-100 rpm, mechanical e f f i c i e n c y decreased from 2454 to 2054 i n slow twitch muscle f i b e r s . McCann and Gliner [1982] reported no s i g n i f i c a n t d i f f e r e n c e between mechanical e f f i c i e n c y and pedalling speeds at a c e r t a i n work rate. Gaesser and Brooks [1975] observed increased net e f f i c i e n c y with increase i n power l e v e l s but considered these to be computational a r t i f a c t s . A l l formulas of e f f i c i e n c y , f o r example, gross, net or mechanical, work or muscle, delta or apparent, regardless of whether one c a l c u l a t e s e f f i c i e n c y using the theoretical-thermodynamic method or t r a d i t i o n a l method (see Appendix A), y i e l d decreasing e f f i c i e n c y with increments i n speed. Aura and Komi [1986] reported that i n p o s i t i v e work mechanical e f f i c i e n c y was inve r s e l y r e l a t e d to the work i n t e n s i t y and angular v e l o c i t y of the j o i n t . The decrease i n mechanical e f f i c i e n c y with increasing work i n t e n s i t y could be explained by the motor unit recruitment patterns at d i f f e r e n t work i n t e n s i t i e s . S p e c i f i c a l l y , the increased force and power output associated with increasing i n t e n s i t i e s of p o s i t i v e work could r e f l e c t the 12 greater recruitment of f a s t - t w i t c h motor units. This i s consistent with the s o - c a l l e d s i z e p r i n c i p l e of motor unit recruitment CHenneman et a l , 19653. The larger f a s t twitch muscle f i b e r s reportedly have a lower mechanical e f f i c i e n c y and economy than the small slow twitch muscle f i b e r s because of greater rate of actomyosin turnover CAwan and Goldspink, 1972; Crow and Kushmerick, 1982; Heglund and Cavagna, 1987; Wendt and Gibbs, 1973 3. Increased recruitment of f a s t twitch f i b e r s would then be expected to lower the o v e r a l l e f f i c i e n c y of the working muscles. Komi et a l C19873 concluded that the f a i r l y constant net mechanical e f f i c i e n c y (ranged between 19% to 275i [Aura and Komi, 1986 3) i n p o s i t i v e work was l i k e l y due to the f a c t that EMG a c t i v i t y , energy expenditure, and mechanical work p a r a l l e l e d changes i n exercise i n t e n s i t y . But when greater contraction v e l o c i t i e s were used, the mechanical e f f i c i e n c y of p o s i t i v e work decreased CAura and Komi, 1986 3. Others [Hansen et a l , 1988; Luhtanen et a l , 19873 reported that isometric work, co-contraction of trunk muscles, elevated body temperature, increased catecholamines, increased 02 uptake i n cardiac and r e s p i r a t o r y muscles can be a d d i t i o n a l causes of decreased e f f i c i e n c y at high work rates. Whipp and Wasserman [19693 observed that t o t a l muscle e f f i c i e n c y derived from a theoretical-thermodynamic perspective, assuming that carbohydrate was the sole metabolic substrate, was s i m i l a r to work e f f i c i e n c y . Thus they promoted the use of the term work e f f i c i e n c y . In contrast, Gaesser and 13 Brooks C19753 reported that the t r a d i t i o n a l method of c a l c u l a t i n g e f f i c i e n c y (based upon oxygen uptake and r e s p i r a t o r y exchange r a t i o ) was judged to be superior to the theoretical-thermodynamic method because i n r e a l l i f e other metabolic substrates are used during exercise evidenced by a r e s p i r a t o r y exchange r a t i o (R) l e s s than 1.0. Furthermore, Gaesser and Brooks [1975 3 a t t r i b u t e d the inconsistencies i n mechanical e f f i c i e n c y reported f o r a given type of work i n the l i t e r a t u r e to d i f f e r e n c e s i n methodology including the s e l e c t i o n of an appropriate baseline c o r r e c t i o n f a c t o r f o r c a l c u l a t i n g e f f i c i e n c y . They claimed that delta e f f i c i e n c y with a ' f l o a t i n g base-line' represented the most accurate estimate of muscular e f f i c i e n c y . The mechanical e f f i c i e n c y of negative work has been reported to range between 61% -116% during cycle ergometry CPahud et a l , 1980; Pimenthal et a l , 1982 3. Komi et a l [1987 3 showed that mechanical e f f i c i e n c y of negative work was d i r e c t l y r e l a t e d to work i n t e n s i t y . On the basis of White's work [1977 3, these i n v e s t i g a t o r s proposed that during e c c e n t r i c muscle contraction, greater force i s produced because of greater resistance at the cross bridge l e v e l when compared to concentric muscle contraction. This proposal can be demonstrated by the f o r c e - v e l o c i t y c h a r a c t e r i s t i c s of s k e l e t a l muscle [Fig. 13. In summary, numerous inco n s i s t e n c i e s e x i s t i n the 14 l i t e r a t u r e regarding the e f f e c t of rate of work (speed) and power (work/time) on the e f f i c i e n c y of p o s i t i v e work. These disagreements r e f l e c t e d the use of d i f f e r e n t d e f i n i t i o n s of e f f i c i e n c y . This resulted i n d i f f e r e n t base l i n e values being subtracted from the gross metabolic consumptions i n various studies giving d i f f e r e n t e f f i c i e n c y values. The more recent l i t e r a t u r e generally agreed that e f f i c i e n c y i s inv e r s e l y r e l a t e d to rate of work and power i n p o s i t i v e work. This observation supports the s i z e p r i n c i p l e of motor unit recruitment CHenneman et a l , 1965], that i s fas t - t w i t c h f i b e r s which are metabolically more expensive are r e c r u i t e d at higher power output. In contrast, the r e s u l t s of the studies i n the l i t e r a t u r e on the e f f i c i e n c y of negative work were more consistent. In negative work, net mechanical e f f i c i e n c y i s d i r e c t l y r e l a t e d to work i n t e n s i t y . This phenomenon can be explained by the f a c t that with increasing v e l o c i t y of stretch, the increases i n force (and work) of the cross bridges are not associated with increases i n motor unit a c t i v a t i o n and energy expenditure [Komi et a l , 19873. lQ22EB2E5tign of Internal Work i n t o C a l c u l a t i o n of E f f i c i e n c y Winter [19793 reported that i t i s important to account f o r i n t e r n a l work i n c a l c u l a t i n g mechanical e f f i c i e n c y . Internal work i s that required to r a i s e and lower the limbs and to produce d i f f e r e n t movement v e l o c i t i e s . When pedall i n g frequency increases and work rate i s constant, the i n t e r n a l 15 work increases [Wells et. a l , 19863. However, when pedalling frequency i s kept, constant, increasing work rate induces no change i n the i n t e r n a l work CLuhtanen et a l , 19873. Wells et a l [1986 3 have shown that by considering the t o t a l power including i n t e r n a l work the diffe r e n c e between the metabolic cost of p o s i t i v e and negative work performed on a cycle ergometer can be reduced. They pointed out that previous i n v e s t i g a t o r s probably overestimated the amount of negative work and underestimated the amount of p o s i t i v e work that was done by the musculature by not includ i n g i n t e r n a l work i n t h e i r c a l c u l a t i o n s . In summary, both the numerator and denominator of the e f f i c i e n c y c a l c u l a t i o n have been questioned i n the l i t e r a t u r e . More d e t a i l e d discussion on e f f i c i e n c y appears i n Appendix A and more d e t a i l e d discussion of i n t e r n a l work appears i n Appendix B. Investigators need to come to some agreement about the term e f f i c i e n c y i n evaluating muscle work and develop a standardized and v a l i d d e f i n i t i o n of e f f i c i e n c y . Also the issue of i n t e r n a l work has to be addressed i n future studies. For the purpose of t h i s present s e r i e s of studies, we propose to assess e f f i c i e n c y p r i m a r i l y on the basis of economy of energy u t i l i z a t i o n , and thereby avert the dilemmas associated with a discussion of ' e f f i c i e n c y ' discussed above. 16 IV EFFECT OF AGING ON ACUTE EXERCISE RESPONSES Aging i s a continuous process from b i r t h . While i t s e f f e c t i s o f f s e t by rapid growth during childhood and adolescence, by the t h i r d decade i n l i f e the e f f e c t of aging becomes noticable. A l l bodily systems are affected to varying extents CMcArdle et a l , 1986; Shephard, 1987; Skinner, 19873. I n i t i a l l y , f u n c t i o n a l reserves are decreased with l i t t l e change in physical function. With time, f u n c t i o n a l impairment can appear e s p e c i a l l y under s t r e s s or during exercise. We have been p a r t i c u l a r l y interested i n studying the p o t e n t i a l r o l e of negative work as a therapeutic intervention fo r c h r o n i c a l l y - d i s a b l e d populations. However, the r e l a t i v e l y few studies on negative work that appear i n the l i t e r a t u r e have involved young healthy subjects [Aura and Komi, 1986; Clarkson and Tremblay, 1988; Davies and Barnes, 1972a,b; Dick and Cavanagh, 1987; Hesser et a l , 1977; Komi et a l , 1987; Pandolf et a l , 1978; Pimental et a l , 1982 3. Thus, although e f f e c t s of aging on the body are well known CMcArdle et a l , 1986; Shephard, 1987; Skinner, 1987; Silbermann et a l , 1983; Vandervoort et a l , 1986 3, the exercise responses of older subjects to negative work have not been described previously. E f f e c t of Aging on the Cardiorespiratory System Various studies [Bates, 1989; Jones, 1988; McArdle et 17 a l , 1986; Shephard, 1987; Skinner, 1987] have reported that pulmonary function and e l a s t i c r e c o i l of the lung decrease with age. Consequently, pulmonary function measures such as forced v i t a l capacity (FVC), forced expiratory volume i n one second (FEV1), FEV1/FVC, t i d a l volume (VT), maximum voluntary v e n t i l a t i o n (MW) and expiratory flow rate are decreased compared to young healthy subjects. The r e s i d u a l volume and c l o s i n g volume also increase with age. Alveolar v e n t i l a t i o n decreases with age l a r g e l y because of progressive destruction of alveolar and c a p i l l a r y surface. The reduction i n d i f f u s i o n capacity of the lung and increased proportion of lung units with low v e n t i l a t i o n perfusion r a t i o (VA/Q) at r e s t can explain the decrease i n a r t e r i a l oxygen p a r t i a l pressure (Pa02) and the increase i n the a l v e o l a r - a r t e r i a l oxygen p a r t i a l pressure gradient at rest. The c e n t r a l responses to hypoxia and hypercapnia are blunted with age. Aging has also been associated with s t i f f e n i n g of the chest wall and c o s t a l v e r t e b r a l j o i n t s CShepard, 1987], and increasing bone l o s s i n the vertebrae [Skinner, 1987; Smith et a l , 1982] r e s u l t i n g i n thoracic kyphosis. These f a c t o r s can contribute to an increased cost of breathing. Older subjects reach peak VT (approximately 5754 VC) at a lower VE than young subjects and therefore have to r e l y on increasing r e s p i r a t o r y rate to further increase VE CDeVries and Adams, 1972]. The v e n t i l a t o r y equivalent f o r oxygen i . e . minute v e n t i l a t i o n / oxygen uptake (VE/V02) has also been shown to increase with age i n d i c a t i n g a l e s s e f f i c i e n t v e n t i l a t o r y system [Shephard, 1987; Skinner, 18 1970 3. Maximum oxygen uptake <V02max> decreases by about 0.4 to 0.9 ml/kg/min each year a f t e r the second decade of l i f e [Dehn and Bruce, 1972; Larson and Bruce, 1986; Skinner, 19813. The maximum heart rate, stroke volume and cardiac output s i m i l a r l y decrease with age CAstrand, 1967; Shephard, 1987; Skinner, 19703. Older people tend to have a higher incidence of anemia which may further decrease the oxygen carrying capacity of the blood CShepard, 1987 3. The decrease i n V02max i s thought to be re l a t e d to decreased oxygen transport CMcArdle et a l , 1986, Skinner, 19703. The recovery time of heart rate post exercise i s longer f o r the older than the younger person. ECG abnormalites are more prevalent in the e l d e r l y CAstrand, 1963; Skinner, 19703 thus close monitoring during exercise t e s t i n g i s e s s e n t i a l CMcArdle et a l , 1986; Skinner, 1987 3. Pulmonary resistance increases somewhat with age CBates, 1989 3 but peripheral vascular resistance and a r t e r i a l wall s t i f f n e s s tend to be higher at res t and during exercise leading to a higher systemic blood pressure CShepard, 1987; Skinner, 1970 3. The skin blood flow i s higher i n the e l d e r l y because of an impaired a b i l i t y to lose heat therefore d i v e r t i n g blood flow away from the exercising muscles. Blood flow to the exercising muscle i s also l i m i t e d to a greater extent i n the older person at a given muscular pressure than i n a younger person. Hence, oxygen d e l i v e r y to the exer c i s i n g muscles i s further lowered i n older subjects CShephard, 1987 3. Consequently, f o r a given 19 work rate, blood l a c t a t e concentration i s higher i n the older subject [Skinner, 1970]. Thus, o v e r a l l , older subjects tend to have a l e s s e f f i c i e n t c a r d i o r e s p i r a t o r y system than young healthy subjects, and are l e s s able to adapt e f f i c i e n t l y to increased c a r d i o r e s p i r a t o r y demands. E f f e c t of Aging on S k e l e t a l Muscle Aging i s associated with a decrease i n lean body mass. This decrease i n muscle mass i s due to the l o s s of muscle protein and progressive replacement with connective t i s s u e and f a t c e l l s [McArdle et a l , 1986; Silbermann et a l , 1983]. At the same time muscle strength decreases minimally between 30 to 55 years of age. After the f i f t h decade, muscle strength decreases sharply with age [McArdle et a l , 1986; Shephard, 1987; Shock and Norris, 1970; Vandervoort et a l , 1986]. Vandervoort et a l [1986] reported that the mean maximum voluntary contraction f o r a muscle group i s more than 20% lower i n i n d i v i d u a l s over 70 years of age compared with younger people. Reduced neuromuscular coordination i s another f a c t o r that contributes to the decrease i n maximum power output observed i n older subjects [Shock and Norris, 1970], I s o k i n e t i c muscle torque measured at high v e l o c i t y drops s i g n i f i c a n t l y with age [Larson et a l , 1979; Shephard, 19871. The number of f a s t - t w i t c h f i b e r s also has been shown to decrease with age i n humans [Grimby and S a l t i n , 1983; Shephard et a l , 1987; Vanderoort et a l , 1986] while Silbermann et a l 20 C19833 using an animal model reported a decrease i n slow-twitch f i b e r s . Machinery involved i n e x c i t a t i o n - c o n t r a c t i o n coupling such as the neuromuscular junction, T-tubules, sarcoplasmic reticulum, and other c e l l structures such as the sarcolemma, Z-l i n e and mitochondria also exhibited age-related changes CShephard, 1987; Vandervoort et a l , 1986 3. In summary, the body undergoes considerable changes with age e s p e c i a l l y a f t e r the f i f t h decade. Body systems tend to function l e s s e f f i c i e n t l y i n the e l d e r l y . Shephard et a l [19883 have at t r i b u t e d the reduction i n physical work capacity i n the e l d e r l y to peripheral as well as c e n t r a l mechanisms. V RATIONALE FOR STUDY Although our knowledge of the p h y s i o l o g i c a l c h a r a c t e r i s t i c s of negative work has grown since the work of Abbott and co-workers almost 40 years ago, the l i t e r a t u r e on negative work i s scant compared to p o s i t i v e work. Studies that have been reported on negative work have focused on the r e l a t i o n of force to power generation, energy consumption and e f f i c i e n c y , electromyographic a c t i v i t y , cardiovascular responses, heat regulation, and muscle damage [Abbott and Bigland, 1953; Abbott et a l , 1952; Armstrong, 1985; Asmussen et a l , 1953; Asmussen et a l , 1956; Aura et a l , 1986; Bigland-R i t c h i e et a l , 1976; Clarkson and Tremblay, 1988; Eloranta et a l , 1980; Friden et a l , 1981; Hesser et a l , 1977; Klausen et 21 a l , 1971; Komi et a l , 1972; Komi et a l , 1987; Knuttgen et a l , 1971a; Knuttgen et a l , 1971b; Moritani et a l , 1988; Newham, 1988; Newham et a l , 1988; Nielson et a l , 1972; Thomson, 19713. With respect to v e n t i l a t i o n during negative work, previous studies have l a r g e l y reported a commensurate drop i n VE which p a r a l l e l s the decrease i n V02 when compared with p o s i t i v e work across the same work rates [Knuttgen et a l , 1971a, Knuttgen et a l , 1971b, Thomson, 19713. Although some studies have examined gross v e n t i l a t o r y changes i n VE during negative work, l i t t l e i s known about the s p e c i f i c e f f e c t s on the components of VE, namely t i d a l volume (VT) and breathing frequency (fb) [Knuttgen et a l , 1971a, Knuttgen et a l , 1971b, Thomson, 19713. Dean and Ross [19893 reported rapid shallow breathing i n healthy subjects during downhill walking on a tre a d m i l l at 3. 5 mph with a -7Y. grade. They further observed that the fb and VT during negative work in t h e i r study were not consistent with the notion that downhill walking i s merely a low-intensity form of p o s i t i v e work. These i n v e s t i g a t o r s argued that postural d i s t o r t i o n of the chest wall, r e s t r i c t i o n of abdominal wall motion or both during downhill walking may contribute to the rapid shallow breathing response observed. In order to minimize any e f f e c t of postural d i s t o r t i o n , we used a cycle ergometer rather than t r e a d m i l l i n the present study. Thus, the present study which extends the previous work of Dean and Ross i n our laboratory w i l l hopefully shed further l i g h t on the e f f e c t of negative 22 work on the components of v e n t i l a t i o n . In addition to the reduced energy cost of negative compared with p o s i t i v e work, the energy cost of a given work rate may be affected by the pedalling frequency. The existence of optimal walking and p e d a l l i n g frequencies f o r i n d i v i d u a l s has been reported CAbbott and Aubert, 1952; Banister and Jackson, 1967; Benedict and Parmenter, 1928; Knuttgen et a l , 1971a; Seabury et a l , 19773. Banister and Jackson reported that a low work rate achieved with a high p e d a l l i n g frequency and low resistance i s metabolically equivalent to a much higher work rate which i s achieved with a low pedalling frequency and high resistance. The existence of optimal pedalling frequencies f o r d i f f e r e n t work rates during p o s i t i v e work has been i d e n t i f i e d , however such values f o r negative work are l e s s clear. The l i t e r a t u r e to date on negative work i n general, and that on p o s i t i v e work examining energy cost at d i f f e r e n t work rates, has p r i m a r i l y reported the responses of young healthy male subjects CAura and Komi, 1986; Davies and Barnes, 1972a,b; Dick and Cavanagh, 1978; Hesser et a l , 1977; Komi et a l , 1987; Pandolf et al,1978; Pimental et a l , 19823. Despite the well-known p h y s i o l o g i c a l consequences of aging [Shephard, 1987; Skinner, 1987; Vandervoort et a l , 19863, and age-related changes i n the responses to conventional exercise during p o s i t i v e work, the responses of older adults to negative work 23 are not known. Because of our long-term; i n t e r e s t i n i n v e s t i g a t i n g the therapeutic p o t e n t i a l of negative work i n the r e h a b i l i t a t i o n of older and disabled i n d i v i d u a l s , t h i s study was designed to examine the exercise responses of middle-aged men. In addition, t h i s study would also provide information about the a b i l i t y of middle-aged men to u t i l i z e stored p o t e n t i a l energy during negative work. In summary, t h i s t h e s i s w i l l help to elucidate the responses of p o s i t i v e vs negative work at d i f f e r e n t pedalling frequencies i n middle-aged men. S p e c i f i c a l l y , t h i s research w i l l provide i n s i g h t i n t o whether negative work performed on a c y c l e ergometer i s equivalent to low ' i n t e n s i t y ' p o s i t i v e work when performed at the same work rate or whether negative work e l i c i t s p h y s i o l o g i c a l l y - d i s t i n c t responses compared with p o s i t i v e work. V I T H E S I S Q U E S T I O N S The s p e c i f i c questions addressed i n t h i s study are:-1. What are the e f f e c t s of p o s i t i v e and negative work on oxygen consumption (V02) and heart rate (HR) when performed by middle-aged men on a c y c l e ergometer? 2. Under these conditions, what are the e f f e c t s of p o s i t i v e and negative work on minute v e n t i l a t i o n (VE), t i d a l volume (VT), 24 and breathing frequency (fb)? 3. What are the e f f e c t s of the three pedalling frequencies on V02, HR, VE, VT and fb? 4. Are the r e l a t i o n s h i p s of VT and VE, and fb and VE d i f f e r e n t i n p o s i t i v e and negative work? 5. Are the r e l a t i o n s h i p s of VE and V02 and HR and V02 d i f f e r e n t i n p o s i t i v e and negative work? 25 Fig. 1 Force v e l o c i t y curve for muscle shortening contraction or p o s i t i v e work ( s o l i d l i n e ) and muscle lengthening contraction or negative work ( s o l i d l i n e ) . As the load (V) decreases u n t i l V=0 when P = Po, maximal isometric tension, i s reached. As forces greater than Po are applied, the muscle lengthens. Power (force x speed) i s produced during shortening - broken l i n e ; absorbed during lengthening - broken l i n e . 26 SPEED V Lengthening O Shortening s i / 1 s / / •o s> i / / / / / / / / \ I METHODS I RESEARCH DESIGN We used a 2 (p o s i t i v e and negative work) by 3 (35, 5 5 , 75 rpm pedalling frequencies) f a c t o r i a l design with repeated measures on both factors. Each subject performed six tests, s p e c i f i c a l l y one at each of the three pedalling frequencies f o r each of the two types of muscle work. Power was held constant, s p e c i f i c a l l y , 60 Watt f o r a l l t e s t s . Subjects were randomly selected to perform p o s i t i v e or negative work on the f i r s t o f two tes t days which were scheduled one week apart. The o r d e r of the pedalling frequencies was also randomly selected by each subject at the beginning of each te s t by means of card s e l e c t i o n . The exercise responses that were of p a r t i c u l a r i n t e r e s t included oxygen uptake <V02), heart rate (HR), minute v e n t i l a t i o n <VE), t i d a l volume <VT) and breathing frequency (fb). I I S U B J E C T S Twelve healthy middle-aged men with no hist o r y of car d i o r e s p i r a t o r y disease p a r t i c i p a t e d i n the study. No subject had p a r t i c i p a t e d i n any formal exercise program or t r a i n i n g over the past year. A d e t a i l e d explanation of the research design and purpose of the study was given to each subject. Each subject was then asked to sign an informed 28 consent form approved by the University of B r i t i s h Columbia Ethics Committee. I l l EQUIPMENT AND MEASURES Cycle Erggmeter The assembly of the b i c y c l e ergometer i s shown i n Fig. 2. A l l parts were bolted onto two connected r i g i d wooden frames with wheels for easy transportation. Brakes were applied during t e s t i n g to maintain s t a b i l i t y of the assembly. A sturdy chair with arm support was mounted onto the wooden frame on an adjustable linkage to allow optimal leg extension and comfort f o r each subject. The chair was f i x e d so that the subject could s i t approximately l e v e l with the pedals so that the legs were extended forward, rather than downward. A chair with arm support was used to minimize the contribution of s i t t i n g and the movements associated with balancing and body f i x a t i o n to the t o t a l energy cost of c y c l i n g [Knuttgen et a l , 1971b; Hesser et a l , 19771. The center of r o t a t i o n of the subject's ankle j o i n t was positioned close to the center of the pedal to standardize mechanical leverage and equalize thigh and lower leg muscle involvement [Bigland-Ritchie et a l , 1976; Ericson, 1986]. Foot straps were applied to ensure the subject maintained the required foot p o s i t i o n throughout the te s t . 29 A standard cycle ergometer (Monark) was modified by the U.B.C. Health Science Center Bio-medical Engineering Department to perform p o s i t i v e and negative work. The modification followed that described i n the l i t e r a t u r e CBigland-Ritchie et a l , 1973]. The modified cycle ergometer has a 1:3.8 gear r a t i o between the pedals and flywheel. For eit h e r p o s i t i v e or negative work, the flywheel i s driven through a bicycle-chain connected to a 1.5 horsepower d-c motor (Baldor). The d-c motor i s connected to a s o l i d - s t a t e r e v e r s i b l e speed c ontrol. Imposed torque i s determined by measuring the current drawn by the motor. A s i g n a l conditioning c i r c u i t converts measured current to torque (Newtons) which i s displayed on a d i g i t a l meter (Texmate Inc). The speed i s held constant by a constant current feedback control, the output of which i s also displayed by a d i g i t a l output gauge (Minarik magnetic pickup). The pedal frequency con t r o l ranges from 0 to 120 rpm. Maximum allowable torque r e g i s t r a b l e at the pedals i s 70 N for pedal speeds ranging from 40-120 rpm. At pedal speeds l e s s than 40 rpm, the maximum allowable torque i s decreased i n proportion to the decrease in pedal speed. The o r i g i n a l f r i c t i o n b e l t braking system of the ergometer i s retained f o r forward pedalling or p o s i t i v e work and for c a l i b r a t i o n . In t h i s motor-driven cycle ergometer, the peda l l i n g speed i s c o n t r o l l e d by the motor and the load i s co n t r o l l e d by the subject. A second set of speed and torque output gauges are placed i n front of the subject to provide d i r e c t v i s u a l feedback. 30 The control panel i s attached to the frame of the motorized ergometer. The control panel has an on-off control, speed control, forward or reverse control, stop or run control, clutch engage or disengage switch, torque c a l i b r a t i o n , torque zero, and speed c a l i b r a t i o n knobs. The c i r c u i t r y and fuse are contained within the control panel. Both speed and torque c a l i b r a t i o n s were done p r i o r to t e s t i n g and r e c a l i b r a t e d whenever there was a change i n speed or work se t t i n g . Speed c a l i b r a t i o n was done by matching the frequency of the turning pedals with the aid of a stop watch f o r a given speed to the speed output gauge. Subsequently, torque reading was zeroed at each te s t speed. Torque c a l i b r a t i o n was done using the o r i g i n a l f r i c t i o n band on the ergometer as reference i n the forward d i r e c t i o n . The f r i c t i o n band on the ergometer was tightened to a known r e s i s t i v e force and the torque d i g i t a l output gauge was c a l i b r a t e d to match the r e s i s t i v e force. Torque c a l i b r a t i o n f o r the reverse d i r e c t i o n was tested by the U.B.C. Health Science Center Bio-medical Engineering Department by using the o r i g i n a l f r i c t i o n band and a known r e s i s t i v e force and was i d e n t i c a l to the forward d i r e c t i o n . Therefore f o r a given speed, torque c a l i b r a t i o n performed i n the forward d i r e c t i o n also serves to c a l i b r a t e the reverse d i r e c t i o n CG. Sandford, Biomedical Technologist, personal communication]. These procedures constituted the c a l i b r a t i o n f o r each speed f o r both 31 p o s i t i v e and negative work i e . pedalling i n the forward and backward d i r e c t i o n s CBigland-Ritchie et a l , 1973; G. Sandford, Biomedical Technologist, personal communication!. Metabolic Measurement Cart A Sensormedics Metabolic Measurement Cart (MMC) was used during exercise t e s t i n g to perform breath-by-breath gas sampling. Subjects were connected to the MMC by a head-piece assembly and mouth piece. A nose c l i p was used to avoid a i r leakage through the nose. Expired gas was then analyzed over each 15 sec i n t e r v a l during t e s t i n g . Measures included oxygen consumption, minute v e n t i l a t i o n , t i d a l volume and breathing frequency. Before each test, the MMC was c a l i b r a t e d according to the operator-guided c a l i b r a t i o n procedures recommended by the manufacturer using s p e c i f i c c a l i b r a t i o n gases. Heart rate and rhythm were continuously monitored using a three lead ECG monitor (Hewlett-Packard). Oxygen saturation was measured using an Ohmeda oximeter with an ear lobe sensor. Both monitors were c a l i b r a t e d before each test. Analog c i r c u i t r y boards also allowed heart rate and a r t e r i a l saturation to be averaged every 15 seconds and appear on the c o l l e c t i v e data print-out. 32 Other Measures Blood pressure was measured manually using a bra c h i a l c u f f and stethoscope at minute i n t e r v a l s throughout each test by the same experienced i n d i v i d u a l . In addition, subjective measures of breathing d i f f i c u l t y were recorded every minute. Borg's modified scale with r a t i o properties was used to measure breathing d i f f i c u l t y . The scale ranged from 0 or 'nothing at a l l ' to 10 or 'very, very strong' CBorg, 19823. Appendix C describes the breathing d i f f i c u l t y scale i n greater d e t a i l . Tests were c a r r i e d out i n a temperature-controlled exercise laboratory (21 ± 2 C). IV GENERAL PROCEDURES Performance of P o s i t i v e Work The subject was seated f o r forward c y c l i n g or p o s i t i v e work i n the same manner as f o r negative work. The clu t c h of the motor mechanism was engaged i n the forward p o s i t i o n . An extra 10 N load was added onto the pre-determined resistance f o r the subject to prevent damage to the motor by inadvertently d r i v i n g i t above i t s set speed. A lap seat b e l t was fastened to s t a b i l i z e the subject. The standard distance of the chair from the pedals was determined by the length of the f u l l y extended leg and the pedal which was i n the horizontal p o s i t i o n 3 3 furthest, away from the subject. Then the distance of the seat from the pedal was adjusted for subject comfort p r i o r to the s t a r t of t e s t i n g allowing no more than 10 degrees of knee f l e x i o n . Since the tension generated by a muscle i s dependent on i t s r e s t i n g length ( H i l l , 1938), care was taken to ensure that each te s t was performed at a comparable seat p o s i t i o n for each subject. The feet were strapped i n t o p o s i t i o n on the pedals. The subject was encouraged to relax the upper body and trunk while allowing the lower extremities to cycle. After the t e s t speed was set by the tester, the subject pedalled forward to a s s i s t the c y c l e ergometer with s u f f i c i e n t e f f o r t so that the torque output gauge f e l l to 10 N. The motor maintained the speed set by the t e s t e r while the subject a s s i s t e d the movement of the pedals u n t i l the desired torque reading was registered. The subject then maintained the same e f f o r t f o r the duration of the test . E ? £ f o f Negative Work The f r i c t i o n band was l e f t slack while the motor drove the pedals i n the reverse (backward) d i r e c t i o n . At the designated speed set by the tester, the subject was directed to r e s i s t the movement of the pedals u n t i l the desired torque reading was registered. A forced s t r e t c h was therefore imposed on the same muscles that were used to generate power during conventional c y c l i n g using concentric muscle contraction. The work produced by the motor was t r a n s f e r r e d to the active 34 muscles. The rate at which the muscles were 'worked upon' was the power being transferred to the subject [Knuttgen, 1986]. The subject was then t o l d to maintain the l e v e l of resistance f o r the duration of the test. E®r.fQnDirjQfi Qf Free Pedalling For free pedalling p r i o r to p o s i t i v e work, the seated subject placed h i s feet i n the appropriate p o s i t i o n on the pedals and then the feet were strapped i n t o place. He was instru c t e d to relax while the motor drove the feet around at the desired speed. The subject maintained foot contact with the pedals while passively allowing the pedals to carry the legs around forward. During the tes t session, the subject free pedalled at the t e s t speed during the warm up and cool down period. For free p e d a l l i n g p r i o r to negative work, the procedure was the same except that the subject allowed the pedals to carry the legs around i n the backward d i r e c t i o n . P r a c t i c e Sessions A l l subjects attended two to three p r a c t i c e sessions of p o s i t i v e and negative work using the cy c l e ergometer. A subject was deemed to have learned the negative work c y c l i n g technique when he could maintain a given torque output f o r one 35 minute f o r a range of torques determined by the tester. Our i n i t i a l p i l o t work suggested that negative work c y c l i n g was more d i f f i c u l t to learn than p o s i t i v e work c y c l i n g . However, no major d i f f i c u l t y was encountered with the pr a c t i c e and test sessions. P r a c t i c e sessions were also used to f a m i l i a r i z e the subjects with the t e s t i n g environment, general procedures and monitoring equipment. Pr a c t i c e sessions lasted an average of 25 minutes and were purposefully designed to promote a learning e f f e c t while minimizing any t r a i n i n g e f f e c t . Test Protocol Upon completion of the pr a c t i c e sessions, subjects were then e l i g i b l e to p a r t i c i p a t e i n the two tes t conditions, s p e c i f i c a l l y p o s i t i v e and negative work using the cycle ergometer. Tests were conducted at le a s t one week apart. Subjects were requested not to have a large meal at le a s t three hours p r i o r to t e s t i n g and not to consume any substances that contain stimulants (such as coffee or s o f t drinks with c a f f e i n e ) . They were asked to have a r e s t f u l 24 hr period p r i o r to t e s t i n g and to wear comfortable a t t i r e and shoes when they v i s i t e d the laboratory. When a subject a r r i v e d at the exercise labortory on each t e s t day, height and weight were taken and routine pulmonary function t e s t i n g including three t r i a l s of forced 36 expiratory maneuvers, was performed. Subsequently, the subject relaxed while seated on the t e s t i n g chair which was adjusted fo r leg length and comfort, for at lea s t f i v e minutes. Two active electrodes were placed b i l a t e r a l l y over the upper trapezius area and the ground electrode was placed over the l a t e r a l chest f o r ECG monitoring. The subject was then connected to the MMC by means of the head-piece assembly and mouth piece, and a nose c l i p was applied. The subject i n s p i r e d room a i r v i a a low resistance, one-way, non-rebreathing valve. The subject was then again asked to relax i n t h i s comfortable p o s i t i o n f o r another three minutes while r e s t i n g metabolic measures were taken. Baseline p h y s i o l o g i c a l measures were usually taken i n the second to t h i r d minute of the test when V02 and HR of the subject had s t a b i l i z e d . After warming up with f r e e pedalling f o r two minutes, the subject pedalled at the assigned speed (the f i r s t of the three randomized speeds) and power output. A steady-state was defined as the state at which the heart rate and V02 had s t a b i l i z e d . After a steady-state was reached (usually within three minutes) data were c o l l e c t e d f o r f i v e to seven minutes before the t e s t at the assigned speed was terminated. The subject free pedalled during the cool down period f o r several minutes. V i t a l signs were continuously monitored u n t i l they were within 10 to 153* of baseline. The subject then rested f o r 30 minutes p r i o r to being tested at the next speed. This procedure was continued u n t i l a l l three speeds were completed. This protocol was repeated on the second t e s t day f o r the other type of work. 37 The t e s t protocol i s summarized i n Fig.3. V Data Analysis Descriptive s t a t i s t i c s f o r the f i v e dependent variables f o r each of the s i x steady-state t e s t s were calculated. A 2 by 3 (two types of muscle work and three pedalling frequencies) f a c t o r i a l design with repeated measures on both f a c t o r s was used to analyze the data. An ANOVA f o r repeated measures was used f o r each of the f i v e dependent variables. MANOVAs f o r repeated measures were used to analyze the main e f f e c t s f o r ped a l l i n g frequency and the i n t e r a c t i o n when the assumptions f o r ANOVA for repeated measures were v i o l a t e d r e s u l t i n g i n i n f l a t e d p-values [Wilkinson, 19881. Newman-Keuls post hoc t e s t s were used to t e s t the e f f e c t of pedalling frequency when a s i g n i f i c a n t omnibus F was found. Linear regression was used to determine the r e l a t i o n s h i p between VT and VE, fb and VE, HR and V02, and VE and V02 during both p o s i t i v e and negative work. The regression l i n e s f o r each of the four . r e l a t i o n s h i p s were then tested for homogeneity of the regression c o e f f i c i e n t s between p o s i t i v e and negative work. An alpha of l e s s than 0.05 was used as the c r i t i c a l value. 38 Fig.2 Motorized Cycle Ergometer Cycle Ergometer Motor & Clutch Control Panel \ (Speed & Display Torque) Chair 0 it x Frame o o o Locking / Pivoting Wheels 39 Fig.3 Flow diagram of the test protocol Connected to MMC * Rest 5 min I Free Pedal few Steady State Exercise Test 1 2 min <7 min Cool Down 2 min I Disconnected from MMC + Rest for 30 min then Re-tested o RESULTS I SUBJECT CHARACTERISTICS Subjects were healthy men with a mean age of 49.7 years ranging from 39 to 65 years. Their Body Mass Indexes (BMI) averaged 26.1 kg/m.m and ranged from 21.8 to 31.5 kg/m.m. Pulmonary function test r e s u l t s were within normal range for each i n d i v i d u a l (Table I ) . We used Morris' norms t1976 3 for assessing pulmonary function. A l l exercise t e s t s were performed without any untoward episodes. The .average Sa02 was 97X and remained stable throughout exercise testing. Overall, the ECGs were considered to be within normal l i m i t s during rest, exercise and post exercise recovery f o r a l l subjects. The Borg's subjective rating of breathing d i f f i c u l t y was on the average 1.1 and 0.8 units f o r p o s i t i v e and negative work respectively during the steady-state portions of the exercise tests. II OXYGEN CONSUMPTION Descriptive s t a t i s t i c s f o r V02 are shown i n Fig. 4. The baseline values preceding p o s i t i v e and negative work represent a composite mean of the three baseline periods f o r each te s t day. During p o s i t i v e work, V02 (means ± standard deviations) was 1.04+.13, 1.12*.13 and 1.25+.13 1/min f o r 41 pedalling frequencies of 35, 55, and 75 rpm respectively. For negative work, these were 0. 64*. 17, 0. 55+.. 14 and 0. 67 + . 24 1/min for pedalling frequencies of 35, 55, and 75 rpm respectively. The r e s u l t s of the ANOVA are shown i n Table II. Overall, the V02 was lower during negative than p o s i t i v e work (p<0.001) and there was a s i g n i f i c a n t e f f e c t of speed on V02 (p-0.002). Post hoc te s t s revealed that the V02 during p o s i t i v e work was s i g n i f i c a n t l y higher at 75 rpm than at 35 and 55 rpm (p<0.05). During negative work, the V02 was s i g n i f i c a n t l y higher at 75 than 55 rpm. There was also a s i g n i f i c a n t i n t e r a c t i o n (p<0.01) showing that V02 increased l i n e a r l y during p o s i t i v e work while the VQ2 was the lowest at 55 rpm during negative work. I l l HEART RATE Descriptive s t a t i s t i c s (means + standard deviations) fo r HR are shown i n Fig. 5. The baseline values preceding p o s i t i v e and negative work represent a composite mean of the three baseline periods f o r each te s t day. During p o s i t i v e work, the HR was 93.0+9.4, 95.4 + 10.5 and 99.2+12.1 bpm f o r pedalling frequencies of 35, 55, and 75 rpm respectively. For negative work, these were 82.5+11.5, 77.8+14.0 and 85.1 + 15.4 bpm for pedalling frequencies of 35, 55, and 75 rpm respectively. 42 The r e s u l t s of the ANOVA are shown i n Table I I I . Overall, the HR was lower during negative than p o s i t i v e work (p<0.001) with a s i g n i f i c a n t e f f e c t of speed on heart rate (p=0.003). Post hoc tests revealed that the HR during p o s i t i v e work was s i g n i f i c a n t l y higher at 75 rpm than at 55 and 35 rpm <p<0.05). During negative work, the HR was s i g n i f i c a n t l y higher at 75 than 55 rpm. There was also a s i g n i f i c a n t i n t e r a c t i o n (p<0.05) showing that HR increased l i n e a r l y during p o s i t i v e work while the HR was lowest at 55 rpm during negative work. The r e s u l t s of the scatter plot f o r the HR and V02 re l a t i o n s h i p are shown i n Fig. 6. The s i g n i f i c a n t HR and V02 re l a t i o n s h i p during p o s i t i v e work can be described by the equation HR = 62.1 • <29.8)V02 and the Pearson product-moment co r r e l a t i o n c o e f f i c i e n t (r) which was 0.42 (p<0.05). The s i g n i f i c a n t HR and V02 r e l a t i o n s h i p during negative work can be described by the equation HR = 52.0 • (47.8)V02 and r which was 0.66 (p<0.05). The slopes and intercepts of the regression l i n e s during both p o s i t i v e and negative work for the re l a t i o n s h i p of HR and V02 did not d i f f e r (p>0.05). I V M I N U T E V E N T I L A T I O N Descriptive s t a t i s t i c s (means + standard deviations) for VE are shown i n Fig. 7. The baseline values preceding p o s i t i v e and negative work represent a composite mean of the 43 three baseline periods for each te s t day. During p o s i t i v e work, the VE was 24.6 + 4.9, 26. 2+.5. 7 and 29.4+6.0 1/min for pedalling frequencies of 35, 55 and 75 rpm respectively. For negative work, the VE was 16.0 + 4.1, 14.8 + 4.2 and 18.6+7.2 1/min for pedalling frequencies of 35, 55 and 75 rpm respectively. The r e s u l t s of the ANOVA are shown i n Table IV. Overall, the VE was lower during negative than p o s i t i v e work (p<0.001) with a s i g n i f i c a n t e f f e c t of speed on VE (p<0.01). Post hoc te s t s revealed that the VE during both p o s i t i v e and negative work was s i g n i f i c a n t l y higher at 75 rpm than 55 and 35 rpm for each type of work <p<0.05). There was no in t e r a c t i o n (p>0.05). The r e s u l t s of the scatter plot for the VE and V02 re l a t i o n s h i p are shown i n Fig. 8. The s i g n i f i c a n t r e l a t i o n s h i p of VE and V02 during p o s i t i v e work can be described by the equation VE = -8.86 + (31.4)V02 and r which was 0.81 (p<0.05). The s i g n i f i c a n t VE and V02 r e l a t i o n s h i p during negative work can be described by the equation VE = 1.24 + <24.4)V02 and r which was 0.85 <p<0.05). The slopes of the regression l i n e s during both p o s i t i v e and negative work f o r the VE and V02 re l a t i o n s h i p did not d i f f e r s t a t i s t i c a l l y (p>0.05) while the intercept was s i g n i f i c a n t l y smaller during p o s i t i v e work (p<0.05). 44 V T I D A L VOLUME Descriptive s t a t i s t i c s (means ± standard deviations) for VT are shown i n Fig. 9. The baseline values preceding p o s i t i v e and negative work represent a composite mean of the three baseline periods f o r each te s t day. During p o s i t i v e work, VT was 1.40 + .31, 1.41*. 30 and 1.57 + .35 1/breath for pedalling frequencies of 35, 55, and 75 rpm respectively. For negative work, the VT was 0. 93±. 24, 0.93 + . 29 and 1.12 + .41 1/breath for pedalling frequencies of 35, 55, and 75 rpm respectively. The r e s u l t s of the ANOVA are shown i n Table V. Overall, the VT was lower during negative than p o s i t i v e work (p<0.001) with a s i g n i f i c a n t e f f e c t of speed on VT <p=0.03). Post hoc tes t s revealed that the VT during both p o s i t i v e and negative work at 75 rpm was s i g n i f i c a n t l y higher than at 55 and 35 rpm (p<0.05). The i n t e r a c t i o n was non-significant (p>0.05). The r e s u l t s of the scatter plot f o r the VT and VE re l a t i o n s h i p are shown i n Fig. 10. The s i g n i f i c a n t r e l a t i o n s h i p of VT and VE during p o s i t i v e work can be described by the equation VT = 0.89 + (0.022)VE and r which was 0.39 (p<0.05). The s i g n i f i c a n t VT and VE re l a t i o n s h i p during negative work can be described by the equation VT = 0.51 «• (0.030)VE and r which was 0.49 (p<0.05). The slopes and intercepts of the regression l i n e s during both p o s i t i v e and 45 negative work f o r the VT and VE re l a t i o n s h i p did not d i f f e r <p>0.05). VI BREATHING FREQUENCY Descriptive s t a t i s t i c s (means + standard deviations) for fb are shown i n Fig. 11. The baseline values preceding p o s i t i v e and negative work represent a composite mean of the three baseline periods f o r each test day. During p o s i t i v e work, fb was 18.1+4.1, 18.8 + 3.6 and 19. 3 + . 4. 2 br/min for pedalling frequencies of 35, 55, and 75 rpm respectively. For negative work, the fb was 18.2+6.3, 16.8+.4.7 and 17.5+5.8 br/min f o r pedalling frequencies of 35, 55, and 75 rpm respectively. The r e s u l t s of the ANOVA are shown i n Table VI. There were no differences i n fb between p o s i t i v e and negative work nor among pedalling frequencies (p>0.05). The r e s u l t s of the scatter plot f o r the fb and VE re l a t i o n s h i p are shown i n Fig. 12. The r e l a t i o n s h i p of fb and VE during p o s i t i v e work can be described by the equation fb = 9.62 + (0.34)VE and r which was 0.51 <p<0.05). The re l a t i o n s h i p of fb and VE during negative work can be described by the equation fb = 11.08 + <0.393)VE and r which was 0.39 (p<0. 05). The slopes and intercepts of the regression l i n e s during both p o s i t i v e and negative work for the fb and VE 46 r e l a t i o n s h i p did not d i f f e r <p>0.05). 47 TABLE I SUMMARY OF PULMONARY FUNCTION TESTS AND ANTHROPOMETRIC DATA FOR TWELVE HEALTHY MEN AGE WEIGHT HEIGHT BMI (yr) (kg) (cm) (kg/m.m) Mean 48.7 82.4 177.9 26.1 S.D. 9.3 9.5 5.2 3.1 Minimum 39 66.9 171.5 21.8 Maximum 65 101.1 188.0 31.6 FEV1 FEV1% FVC FVC*/. RATIO RATIO*/. (1) (%) (1) (%) (*/.) (54) Mean 3.89 106 4.93 102 79.5 108 S.D. 0.51 10.1 0.52 7.3 4.9 5.9 Minimum 2.92 92 4.18 90 70 101 Maximum 4.70 124 5.95 113 87 121 ABBREVIATIONS: Ratio i s FEVi/FVC. FEV1% i s the percentage of subject's FEV1 divided by the predicted FEV1 from a nomogram. FVCX i s the percentage of subject's FVC divided by the predicted FVC from a nomogram. Ratio i s the percentage of subject's r a t i o divided by the predicted r a t i o from a nomogram. S.D. i s standard deviation. 48 Fig. 4 Descriptive s t a t i s t i c s f or oxygen consumption for three pedalling frequencies during p o s i t i v e and negative work. V e r t i c a l bars represent standard deviations. Legend: +ve i s p o s i t i v e work. -ve i s negative work. * d i f f e r e n t from 55 rpm <p<0.05). ** d i f f e r e n t from 35 rpm <p<0.05). 49 OXYGEN CONSUMPTION Positive vs Negative Work T A B L E I I OXYGEN CONSUMPTION DURING POSITIVE AND NEGATIVE WORK AT THREE PEDALLING FREQUENCIES. UNIVARIATE AND MULTIVARIATE REPEATED MEASURES ANALYSIS. TEST FOR EFFECT CALLED: TYPE OF WORK (A) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION A 4.713 1 4.713 219.634 0.000 ERROR 0.236 11 0.021 TEST FOR EFFECT CALLED: PEDALLING FREQUENCY <B) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION B 0.239 2 0.119 15.465 0.000 ERROR 0.170 22 0. 008 MULTIVARIATE TEST STATISTICS WILKS' LAMBDA = 0.299 F-STATISTIC = 11.711 DF = 2,10 PROB = 0.002 TEST FOR EFFECT CALLED: INTERACTION <A X B) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION A X B 0.113 2 0.057 7.050 0.004 ERROR 0.176 22 0. 008 51 Fig.5 Descriptive s t a t i s t i c s f o r heart rate for three pedalling frequencies during p o s i t i v e and negative work. V e r t i c a l bars represent standard deviations. Legend: + ve i s p o s i t i v e work. -ve i s negative work. * d i f f e r e n t from 55 rpm <p<0.05). *» d i f f e r e n t from 35 rpm <p<0.05). 52 HEART RATE Positive vs Negative Work HR (bpm) TABLE III HEART RATE DURING POSITIVE AND NEGATIVE WORK AT THREE PEDALLING FREQUENCIES. UNIVARIATE AND MULTIVARIATE REPEATED MEASURES ANALYSIS. TEST FOR EFFECT CALLED: TYPE OF WORK <A> UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION A 3560.273 1 3560.273 49.661 0. 000 ERROR 788.612 11 71.692 TEST FOR EFFECT CALLED: PEDALLING FREQUENCY (B) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION B 414.309 2 207.154 8.411 0.002 ERROR 541.858 22 24.630 MULTIVARIATE TEST STATISTICS WILKS' LAMBDA = 0.317 F-STATISTIC = 10.766 DF = 2, 10 PROB = 0.003 TEST FOR EFFECT CALLED: INTERACTION < A X B) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION A X B 151.585 2 75.793 3.413 0.051 ERROR 488.595 22 22.209 54 Fig.6 Scatter plot of heart rate and oxygen consumption relat i o n s h i p . Legend: HR and V02 values for p o s i t i v e work are represented by 'p'. HR and V02 values f o r negative work are represented by 'n'. The regression l i n e s between po s i t i v e and negative did not d i f f e r <p>0.05) and can be described by a common equation HR = 61.2 + 31.5<V02) with r=0.69 and standard error of estimate <SEE> = 10.3. 55 Heart Rate (bpm) 140 1 1 1 1 1 1 "" '" 1 P 122 P n • 104 P PP P P P n n nn " P P n nn P P PPP_— 86 nn n "PP P n n nn n -« p p ^ P P P P P • " n - — — P n n 68 n n nn n 50 i i i • i i i 0 3 0.5 0.7 0.9 1.1 1 .3 1.5 Oxygen Consumption (1/rain) Fig.7 Descriptive s t a t i s t i c s f or minute v e n t i l a t i o n for three pedalling frequencies during p o s i t i v e and negative work. V e r t i c a l bars represent standard deviations. Legend: +ve i s p o s i t i v e work. -ve i s negative work. • d i f f e r e n t from 55 rpm <p<0.05). *» d i f f e r e n t from 35 rpm <p<0.05). 57 MINUTE VENTILATION Positive vs Negative Work VE (1/min) BASELINE 75 TABLE IV MINUTE VENTILATION DURING POSITIVE AND NEGATIVE WORK AT THREE PEDALLING FREQUENCIES. UNIVARIATE AND MULTIVARIATE REPEATED MEASURES ANALYSIS. TEST FOR EFFECT CALLED: TYPE OF WORK <A> UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS OF VARIATION A 1901.594 1 1901.594 ERROR 224.341 11 20.395 TEST FOR EFFECT CALLED: PEDALLING FREQUENCY <B) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION B 210.611 2 105.306 11.806 0.000 ERROR 196.228 22 8.919 MULTIVARIATE TEST STATISTICS WILKS' LAMBDA = 0.394 F-STATISTIC = 7.684 DF = 2, 10 PROB = 0.010 F P 93.240 0.000 TEST FOR EFFECT CALLED: INTERACTION (A X B) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION A X B 26.604 2 13.302 3.370 0.053 ERROR 86.844 22 3. 947 59 Fig.8 Scatter plot of minute v e n t i l a t i o n and oxygen consumption relationship. Legend: VE and V02 values for p o s i t i v e work are represented by 'p'. VE and V02 values for negative work are represented by 'n'. The slopes of the regression l i n e s between p o s i t i v e and negative did not d i f f e r <p>0.05). However, the intercepts d i f f e r e d between p o s i t i v e and negative work <p<0.05). The common slope of the regression l i n e was 22.2(V02). For p o s i t i v e work, the intercept was -8.9 with r=0.81 and SEE=3.45. For negative work, the intercept was 1.2 with r=0.85 and SEE=3.0. 60 Minute Ventilation (1/min) Oxygen Consumption (1/mln) Fig.9 Descriptive s t a t i s t i c s f or t i d a l volume f o r three pedalling frequencies during p o s i t i v e and negative work. V e r t i c a l bars represent standard deviations. Legend: +ve i s p o s i t i v e work. -ve i s negative work. » d i f f e r e n t from 55 rpm <p<0.05). ** d i f f e r e n t from 35 rpm (p<0.05). 62 TIDAL VOLUME Positive vs Negative Work VT (1/br) 2.0 i TABLE V TIDAL VOLUME DURING POSITIVE AND NEGATIVE WORK AT THREE PEDALLING FREQUENCIES. UNIVARIATE AND MULTIVARIATE REPEATED MEASURES ANALYSIS. TEST FOR EFFECT CALLED: TYPE OF WORK <A> UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION A 3.926 1 3.926 56.818 0.000 ERROR 0.760 11 0.069 TEST FOR EFFECT CALLED: PEDALLING FREQUENCY (B) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION B 0.497 2 0.248 7.619 0.003 ERROR 0.717 22 0.033 MULTIVARIATE TEST STATISTICS WILKS' LAMBDA = 0.523 F-STATISTIC = 4.559 DF = 2, 10 PROB = 0.039 TEST FOR EFFECT CALLED: INTERACTION (A X B) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION C 0.006 2 0.003 0.275 0. 762 ERROR 0.248 22 0.011 64 Fig.10 Scatter plot of t i d a l volume and minute v e n t i l a t i o n r e l a t i o n s h i p . Legend: VT and VE values for p o s i t i v e vork are represented by 'p'. VT and VE values for negative work are represented by 'n'. The regression l i n e s between p o s i t i v e and negative did not d i f f e r (p>0.05) and can be described by a common equation VT = 0.48 + 0.035(VE) with r=0.66 and SEE=0.30. 65 Fig.11 Descriptive s t a t i s t i c s for breathing frequency for three pedalling frequencies during p o s i t i v e and negative work. V e r t i c a l bars represent standard deviations. Legend: +ve i s p o s i t i v e work. -ve i s negative work. 67 BREATHING FREQUENCY Positive vs Negative Work f b ( b r / m i n ) BASELINE 35 55 Pedalling Frequency (rpm) I Positive Work i H H Negative Work 75 TABLE VI BREATHING FREQUENCY DURING POSITIVE AND NEGATIVE WORK AT THREE PEDALLING FREQUENCIES. UNIVARIATE AND MULTIVARIATE REPEATED MEASURES ANALYSIS. TEST FOR EFFECT CALLED: TYPE OF WORK (A) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION A 27.851 1 27.851 1.824 0.204 ERROR 167.983 11 15.271 TEST FOR EFFECT CALLED: PEDALLING FREQUENCY <B) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION B 4.132 2 2.066 0.480 0.627 ERROR 94.646 22 4.302 TEST FOR EFFECT CALLED: INTERACTION (A X B) UNIVARIATE REPEATED MEASURES F-TEST SOURCE SS DF MS F P OF VARIATION A X B 19.008 2 9.504 3.854 0.037 ERROR 54.256 22 2.466 MULTIVARIATE TEST STATISTICS WILKS' LAMBDA = 0.564 F-STATISTIC = 3.863 DF = 2, 10 PROB = 0.057 69 Fig. 12 Scatter plot of breathing frequency and minute v e n t i l a t i o n relationship. Legend: fb and VE values for po s i t i v e work are represented by 'p'. fb and VE values for negative work are represented by 'n' . The regression l i n e s between p o s i t i v e and negative did not d i f f e r <p>0.05) and can be described by a common equation fb = 12.7 + 0.25<VE) with r=0.40 and SEE = 4.4. 70 Breathing Frequency (bpm) 6 15 24 33 Minute V e n t i l a t i o n (1/min) 42 DISCUSSION The 12 subjects who participated i n t h i s study represented a cross-section of healthy middle-aged men based upon pulmonary function tests, body mass index (although t h i s tended to be on the higher side), ECGs, and the absence of resting and exercise-induced a r t e r i a l desaturation. As predicted for these healthy subjects, the constant work rate o only 60 Watts f o r both p o s i t i v e and negative work was generall associated with reports of minimal exertion. I EFFECTS OF STEADY-STATE CYCLING ON OXYGEN CONSUMPTION Oxygen consumption during negative work was about 55*/. that for p o s i t i v e work at the same work output of 60 Watts. There was more v a r i a t i o n i n V02 between subjects during negative than p o s i t i v e work. The lower oxygen consumption associated with negative work i s well established i n the l i t e r a t u r e [Abbott et a l , 1952; Abbott and Bigland, 1953; Asmussen, 1953; Aura and Komi, 1986; Bigland-Ritchie and Wood, 1976; Hesser et a l , 1977; Knuttgen et a l , 1971a,b; Komi et a l , 1987 3. At correspondingly low work rates of 60 Watts, these studies reported that the energy cost measured by oxygen uptak during negative work ranged from 45 to 65% of p o s i t i v e work [Abbott et a l , 1952; Bigland-Ritchie and Wood, 1976, Hesser et a l , 1977; Knuttgen et a l , 1971a,b3. The c o e f f i c i e n t s of va r i a t i o n or CV (standard v a r i a t i o n divided by the mean) 72 reported i n the l i t e r a t u r e for negative work range from 1.4 to 4.4 times those reported for p o s i t i v e work [Bigland-Ritchie and Woods, 1976; Dick and Cavanagh, 1987; Hesser et a l , 1977; Knuttgen, 1986]. In t h i s study, the average CV f o r negative work was about two and a half times that for p o s i t i v e work. The lower oxygen consumption can be explained by the higher " e f f i c i e n c y " of negative work CAbbott et a l , 1952; Abbott and Bigland, 1953; Asmussen, 1953; Aura and Komi, 1986; Bigland-Ritchie and Wood, 1976; Hesser et a l , 1977; Knuttgen et a l , 1971a,b; Komi et a l , 1987]. However, the higher c o e f f i c i e n t of va r i a t i o n associated with negative work has not been explained in the l i t e r a t u r e . In t h i s study, three f a c t o r s could have p o t e n t i a l l y influenced the greater v a r i a t i o n observed during negative work. The f i r s t factor involves the novelty of negative work using cycle ergometry, even though a l l subjects had had three practice sessions and were deemed to have attained the necessary s k i l l f o r the tes t sessions. However the work output appeared to flu c t u a t e more during negative than p o s i t i v e work. More practice sessions may attenuate these fluctuations. The second fa c t o r i s that negative work may demand more concentration from the subjects. Constancy of work output during negative work was prone to being disrupted during blood pressure measurements and when the subject responded to the breathlessness scale. Even though these interruptions were simulated c l o s e l y during the practice session, more habituation 73 to negative work may decrease the concentration required during negative work. Further, by recording power output during exercise would d i r e c t l y e s t a b l i s h any s i g n i f i c a n t difference in v a r i a b i l i t y i n work output between po s i t i v e and negative work. The t h i r d factor could be related to differences i n the degree of muscle co-contraction i n non exercising muscles during p o s i t i v e and negative work. Anecdotally, negative work was often reported to require more attention to perform than p o s i t i v e work. Some subjects appeared to tense t h e i r arms and trunk muscles more than required despite use of a seat b e l t for s t a b i l i z a t i o n . Although more practice sessions could also help address t h i s d i f f i c u l t y , i n c l u s i o n of these could increase the drop out and non-participation rate i n the study. With the current procedure, subjects were required to come to the laboratory on f i v e separate occasions over three weeks. Any increase i n the frequency of attendance and the length of involvement could decrease the number of participants. In summary, oxygen consumption observed i n t h i s study was within the range reported for p o s i t i v e and negative cycle ergometry i n the l i t e r a t u r e . The higher c o e f f i c i e n t of v a r i a t i o n during negative work could be due to the novelty involved i n t h i s a c t i v i t y compared with more conventional forward pedalling during p o s i t i v e work. Banister and Jackson (1967 3 observed large variations i n oxygen consumption when pedalling frequency varied during p o s i t i v e work on a cycle ergometer at a constant power output. 74 A subsequent study by Gaesser and Brook [1975] further i l l u s t r a t e d t h i s point. As observed i n the present study, oxygen consumption increased with pedalling speed during p o s i t i v e work with oxygen consumption being greatest at the highest pedalling speed of 75 rpm. Less i s known about the e f f e c t of pedalling speed on oxygen consumption during negativ work performed at a constant work rate. Previous studies [Knuttgen et a l , 1971a; Komi et a l , 1987] have reported a gentle r i s e i n V02 with increasing work rate during negative work. The increase we observed i n V02 at 75 rpm could be explained by the recruitment of f a s t twitch f i b e r s [Aura and Komi, 1986; Hansen et a l , 1988; Komi et a l , 1987; Luhtanen et a l , 1987]. Furthermore, Knuttgen et a l [1971a,bl reported lowest V02, HR and VE at 60 rpm during negative work when compared to 20 and 100 rpm at a low work rate s i m i l a r to that used i n our study. This i n t e r e s t i n g finding, however, was not explained. Our work needs to be extended to study in d e t a i l the V02 during negative work at intermediate pedalling frequencies such as 55 rpm. Even though V02 at 55 rpm was not s t a t i s t i c a l l y d i f f e r e n t from 35 rpm, further study i s needed t determine i f a pedalling frequency of 55 rpm i s more e f f i c i e n t than lower and higher pedalling frequencies using our model. When VE and HR were plotted against V02 during both p o s i t i v e and negative work, s i g n i f i c a n t l i n e a r r e l a t i o n s h i p s were found (p<0.05). These r e s u l t s also showed that at a work rate of 60 Watts, VE and HR during both p o s i t i v e and negative 75 work increased correspondingly with V02. However, the intercepts of the VE and V02 regression l i n e s d i f f e r e d between po s i t i v e and negative work <p<0. 05). Thomson C19713 reported comparable VE when comparing p o s i t i v e and negative work using a cycle ergometer at the same V02. However, others have reported that both VE and HR were higher during negative than p o s i t i v e work when compared at the same V02 (Dean and Ross, 1989; Knuttgen et a l , 1971a; Knuttgen et a l , 1971b3. The VE and V02 r e l a t i o n s h i p reported i n the present study are s i m i l a r to those reported i n the l i t e r a t u r e [Dean and Ross, 1989; Knuttgen et a l , 1971a; Knuttgen et a l , 1971b3. However, studying a wider range of exercise i n t e n s i t i e s would enable us to examine these r e l a t i o n s h i p s more thoroughly. II EFFECTS OF STEADY-STATE CYCLING ON HEART RATE In t h i s study, the heart rate response followed the same trends as V02 during p o s i t i v e and negative work. Since V02 and HR are highly correlated CAstrand and Rodahl, 1986; McArdle et a l , 19863, t h i s s i m i l a r i t y could be expected. In general, the HR during negative work was about 85% that during p o s i t i v e work. Si m i l a r l y , the lower HR measured at 55 rpm during negative work could be explained by the lower V02. In turn, the lower V02 i s possibly explained on the basis of less muscle co-contraction e l i c i t e d at 55 rpm, which could reduce peripheral vascular resistance, hence lower the heart rate. 76 I l l EFFECTS OF STEADY-STATE CYCLING ON MINUTE VENTILATION AND ITS COMPONENTS Minute v e n t i l a t i o n during both p o s i t i v e and negative was not d i f f e r e n t at 35 and 55 rpm followed by a s i g n i f i c a n t increase at 75 rpm. Moreover, there was no in t e r a c t i o n i n t h i s study r e f l e c t i n g a n e g l i g i b l e difference i n trend between po s i t i v e and negative work. The lower VE at 55 rpm was also reported by Knuttgen et a l C1971a, 1971b]. This phenomenon was l i k e l y related to lower metabolic demand at 55 rpm. Changes i n VE r e f l e c t change in i t s components, VT and fb. In the steady-state component of t h i s study, the fb was s t a t i s t i c a l l y the same f o r a l l three pedalling speeds i n both p o s i t i v e and negative work. Variation i n VT therefore largely explained the change i n VE. However, when VT and fb were plotted against VE during p o s i t i v e and negative work, s i g n i f i c a n t p o s i t i v e l i n e a r r e l a t i o n s h i p s between VT and VE, and fb and VE were found <p<0.05). Furthermore, the regression equation f o r each of these r e l a t i o n s h i p s did not d i f f e r f o r p o s i t i v e and negative work <p>0.05). The po t e n t i a l s i g n i f i c a n c e of these findings, however, needs further c l a r i f i c a t i o n given that the ranges for a l l three variables, i . e , VE, VT and fb, were r e l a t i v e l y small. To i l l u s t r a t e , the mean difference f o r VE between p o s i t i v e and negative work was 15 1/min and the mean difference f o r fb was only 2 br/min. In 77 addition, the mean increase i n VT during exercise ranged from IS*/, to 32*/. of mean FVC. Thus, the change i n VT could explain the increase i n VE i n t h i s ventilatory range. Further, the lowest mean VE, observed at 55 rpm during negative work, could be explained by the low fb (Fig. 11). The v e n t i l a t o r y responses observed i n t h i s study durin low i n t e n s i t y exercise resemble those reported i n the l i t e r a t u r e [Cunningham et a l , 1986; Hey et a l , 1966; Whipp and Pardy, 1986]. In theory, for a given VE, there i s an optimal combination of VT and fb employed which minimizes the work of the respiratory muscles CBellemare and Grassino, 1982; Clark and von Euler, 1971; Cunningham et a l , 1986; Hey et a l , 1966; Whipp and Pardy, 19863. Ventilatory responses have been described as having two stages, namely Range 1 and Range 2, which enable the respiratory system to adapt e f f i c i e n t l y to increasing demands imposed by exertion. Range 1 i s characterized by a small change i n fb with a l i n e a r increase i VT to account for the increase i n VE observed during low l e v e l of exercise i . e. associated with a VT of l e s s than 50X of VC [Cunningham et a l , 1986; Hey et a l , 1966; Whipp and Pardy, 19863. In addition. Range 1 i s characterized by shortening of the expiratory duration (Te) with no change i n i n s p i r a t o r y duration (Ti) [Clark and von Euler, 19713. Range 2 i s characterized by a r e l a t i v e l y constant VT above 50% of VC, while fb accounts for most of the increase i n VE associated with moderate to high i n t e n s i t i e s of exercise [Cunningham et 78 a l , 1986; Whipp and Pardy, 1986]. Both T i and Te are shortened i n Range 2 CClark and von Euler, 1971]. In the present study, the mean VT was below 50% of the mean FVC during both steady-state p o s i t i v e and negative work. In addition, the changes i n fb and VT followed c l o s e l y those described above f o r Range 1. The strong p o s i t i v e l i n e a r r e l a t i o n s h i p between VT and VE i n t h i s study regardless of the type of muscle work, i s consistent with the c h a r a c t e r i s t i c s of Range 1 described by Hey et a l C1966]. The r e s u l t s of our study therefore showed that at a low work rate of 60 Watts, the VT and VE re l a t i o n s h i p during p o s i t i v e work i s q u a l i t a t i v e l y s i m i l a r to that during negative work for the three pedalling frequencies. The re s u l t contrasts that of Dean and Ross [1989] who observed rapid shallow breathing during negative work i n the form of downhill walking on a treadmill. This difference may r e f l e c t the fac t t h e i r subjects were weightbearing whereas ours were not. Thus, greater musculoskeletal afferent stimulation may have been involved i n t h e i r study i n addition to greater a c t i v i t y of the postural muscles to maintain s t a b i l i t y during walking. Although Dean and Ross C1989] also examined healthy subjects, t h e i r protocol involved measurements taken a f t e r two minutes at a given walking i n t e n s i t y whereas measurements i n our study were taken a f t e r at lea s t f i v e minutes of steady-state cy c l i n g . The n e g l i g i b l e change i n fb observed i n our study over 79 the three pedalling frequencies f o r each type of work probably r e f l e c t s the r e l a t i v e l y low in t e n s i t y of the exercise, hence represents the f l a t plateau stage of Range 1. It i s also possible that the n e g l i g i b l e change i n fb r e f l e c t s entrainment of fb to exercise rhythm CBechbache and Duffin, 1971; Hey et a l , 1977; Kay et a l , 1975; Paterson et a l , 19863. Entrainment of fb to exercise rhythm i s characterized by adopting a fb which i s a multiple <subharmonic frequency) of the exercise rhythm CPaterson et a l , 1986 3. The breathing frequencies i n our study were comparable over the three pedalling frequencies fo r each type of work r e s u l t i n g i n an o v e r a l l mean fb of 18 br/min. The mean fb of 18 br/min was approximately the second, t h i r d and fourth subharmonics of pedalling frequencies 35, 55 and 75 rpm chosen i n our study. It can then be argued that the subjects entrained t h e i r fb onto the subharmonic of the exercise rhythm. However, on closer examination of the in d i v i d u a l data, only two subjects entrained t h e i r fb to 18 br/min which i s a multiple of t h e i r exercise rhythm. Furthermore, the VT and VE r e l a t i o n s h i p has a s i g n i f i c a n t p o s i t i v e intercept which does not support any contribution of entrainment of fb to exercise rhythm CWhipp and Pardy, 19863. In summary, the r e l a t i o n s h i p of both fb and VT to VE during both p o s i t i v e and negative work can be described by the Range 1 ve n t i l a t o r y response described i n the l i t e r a t u r e . However, to v e r i f y t h i s conclusion T i and Te w i l l need to be measured i n future studies. 80 IV EFFECTS OF STEADY-STATE CYCLING ON MINUTE VENTILATION AND ITS COMPONENTS: CHANGES FROM BASELINE TO STEADY-STATE EXERCISE In negative work, the increase i n VE from baseline to steady-state exercise was r e l a t i v e l y small compared to pos i t i v e work (Fig. 7). This r e f l e c t s the c h a r a c t e r i s t i c s of negative work, i . e . metabolically less demanding and greater ' e f f i c i e n c y ' compared with p o s i t i v e work. This change i n VE during negative work was associated with r e l a t i v e l y small changes i n VT 0.85 1/br at baseline to 0.93 1/br at 35 and 55 rpm, and 1.12 1/br at 75 rpm (Fig. 9). In contrast, for po s i t i v e work, the increase i n VT were more marked from 0.81 1/br at baseline to 1.4 1/br at 35 and 55 rpm, and 1.57 1/br. Fig. 11 shows that for negative and po s i t i v e work, fb increased s t a t i s t i c a l l y to the same extent from baseline to steady-state exercise. Thus, despite the difference i n VE between p o s i t i v e and negative work at steady-state exercise, the ven t i l a t o r y response from baseline to steady-state exercise at a power output of 60 Watts showed a comparable quantitative increase i n fb for p o s i t i v e and negative work. The difference i n VE for p o s i t i v e and negative work from baseline to steady-state exercise can therefore be explained by a d i f f e r e n t i a l increase i n VT. For negative work, the increase i n VE from baseline to steady-state exercise was large l y effected by an increase i n fb with r e l a t i v e l y small increase i n VT. In contrast, for po s i t i v e work, the increase i n VE from baseline to steady-state 81 exercise was effected by increases i n both VT and fb. Thus, although a comparable quantitative increase i n fb was observed, fo r p o s i t i v e and negative work t h i s increase appears to be disproportionately high i n negative work work given i t s r e l a t i v e l y low i n t e n s i t y compared to p o s i t i v e work. In addition, t h i s observation i s not consistent with the t y p i c a l Range 1 ve n t i l a t o r y response that was evident i n p o s i t i v e work. The predominant increase i n fb during negative work at the onset of exercise has been reported by Dean and Ross [1989 3. However, the mechanism for t h i s v e n t i l a t o r y response to negative work i s not well understood. Dean and Ross [1989 3 who observed rapid shallow breathing during downhill walking acknowledged that t h i s response may be related to fact o r s other than negative work. The r e s u l t s of the,present study, however, support that negative work may indeed contribute. The explanation for t h i s f i n d i n g warrants more detailed investigation. V EXERCISE RESPONSES OF OLDER SUBJECTS TO STEADY-STATE CYCLING Individual v a r i a t i o n i n response to negative work was noted e s p e c i a l l y at the highest pedalling speed of 75 rpm. Two of the oldest subjects f o r example, showed a r e l a t i v e l y high V02, 1.0 and 1.2 1/min, during negative work at 75 rpm. When a box plot [Wilkinson, 1988 3 was used to map the d i s t r i b u t i o n of V02 at 75 rpm during negative work, the subject with a V02 of 82 1.2 1/min was an o u t l i e r . Tests were repeated f o r these two subjects and the r e s u l t s of these were comparable to each of these subjects' i n i t i a l tests. Two factors could explain t h i s i n t e r e s t i n g variant. F i r s t , one subject appeared tense throughout the t e s t sessions p a r t i c u l a r l y during negative work at 75 rpm. The subject needed frequent reminding to relax his upper body. This factor could increase the VQ2 due to isometric muscle work. The greater V02 observed for the other subject, however, was not apparently associated with an increase i n upper body s t a b i l i z a t i o n . An alternate explanation i s that negative work fo r t h i s subject was e s p e c i a l l y novel involving r e l a t i v e l y more concentration and co-ordination to perform than for the other subjects. Shock and Norris C19703 reported that neuromuscular coordination generally decreases with age. Others also have reported a corresponding decrease i n muscle torque at high v e l o c i t i e s of muscle contraction CGrimby and S a l t i n , 1983; Larson et a l , 1979; Shephard, 19873 and i n the number of motor units [Grimby and S a l t i n , 19833. Vandervoort et a l C19863 has reported that older subjects did not perform a c t i v i t i e s requiring rapid muscle contraction well. In t h i s case, i t i s possible that other muscle groups not normally involved i n performing negative work were recruited. This additional muscle work could explain the increase i n V02. Another hypothesis i s that age-related changes of the s e r i e s e l a s t i c component reduce the muscle's a b i l i t y to harness e l a s t i c energy during negative work. Aging has been reported to induce degenerative changes i n the f i b r o - e l a s t i c tissue 83 tShephard, 19873 which may also a f f e c t the series e l a s t i c component of muscle. Thus, older persons may lose the normal i n t e g r i t y of the f i b r o - e l a s t i c connective tissue, hence series e l a s t i c component, making i t less able to perform negative work e f f i c i e n t l y . This hypothesis was not examined i n t h i s study. Two patients with i n t e r s t i t i a l lung disease who were studied in our laboratory and who were s i m i l a r i n age to these two subjects did not show t h i s exaggerated increase i n V02 at 75 rpm during negative work (Appendix D). VI LIMITATIONS OF THE STUDY L i t t l e i s known about the biomechanics of c y c l i n g a motorized cycle ergometer such as that used i n the present study. The exact proportions of p o s i t i v e and negative work performed are unknown. Studies are needed to investigate the biomechanics of p o s i t i v e and negative work performed on a motorized ergometer. Because a small sample s i z e of 12 subjects was used for t h i s study, low s t a t i s t i c a l power or a high p r o b a b i l i t y of Type II error can be assumed CGlantz, 1987; Shavelson, 1988 3. In the present study, f i v e variables were examined using a 2 by 3 (two types of muscle work by three pedalling speeds) f a c t o r i a l design with repeated measures on both factors. Computation of s t a t i s t i c a l power for each s i n g l e contrast i s complex. However, we observed 10 s t a t i s t i c a l l y s i g n i f i c a n t findings out 84 of the 15 possible sources of va r i a t i o n consisting of two main e f f e c t s and the in t e r a c t i o n for each of the f i v e variables. Thus, the o v e r a l l s t a t i s t i c a l power i n t h i s study appears adequate with 12 subjects. E f f e c t s i z e i s the difference between the two test values for a given dependent variable divided by the standard deviation of the pre-test value [Shavelson, 1988; Olejnik, 1983; Cohen, 1977]. Large e f f e c t s i z e and high c o r r e l a t i o n between test values enhances the ov e r a l l s t a t i s t i c a l power COlejnik, 1983; Cohen, 1977]. With the variable fb, no s t a t i s t i c a l l y s i g n i f i c a n t e f f e c t s were detected. This may be explained by a small e f f e c t s i z e as defined by Cohen C1977]. Because of the small differences observed i n fb among a l l test conditions, a larger sample s i z e may detect a s i g n i f i c a n t difference. However, the small range of values for VE that were observed and the c h a r a c t e r i s t i c s of ven t i l a t o r y response associated with Range 1 can explain the non-significant findings associated with fb. Conversely, since multiple univariate F tests were used to analyze the data i n t h i s study with an alpha l e v e l of 0.05, an o v e r a l l Type 1 error rate of about 20% i s expected t h e o r e t i c a l l y . This rate of o v e r a l l Type I error rate i n experiments i s not uncommon i n the l i t e r a t u r e [Chung et a l , 1989]. Decreasing the alpha f o r F tests f o r each of the f i v e dependent variables w i l l lower the o v e r a l l p r o b a b i l i t y of experimental Type I error but t h i s i s at the expense of increasing the p r o b a b i l i t y of a Type II error. An al t e r n a t i v e 85 i s to use multivariate ANOVA for repeated measures such as doubly multivariate ANOVA and multiple mixed model MANOVA, to reduce the pro b a b i l i t y of making a Type I error. However, c r i t e r i a for selecting multivariate tests and subsequent F test s are not commonly agreed upon tSchutz and Gessaroli, 19851. For these reasons conventional univariate F tests were selected to analyze the data. Two of the oldest subjects had the highest V02 and other associated measures during negative work at 75 rpm. Further studies using subjects older than s i x t y and pedalling speeds greater than 75 rpm could provide more insight i n t o t h i s i n t e r e s t i n g finding. A larger sample s i z e would also further improve the s t a t i s t i c a l power and decrease the influence of skewed data inherent i n a small sample si z e . The motorized cycle ergometer was observed to produce a s l i g h t upward d r i f t i n f r i c t i o n a l resistance at high speeds. This could be due to the vib r a t i o n of the platform where the motor was mounted a f f e c t i n g the spring that regulates the tension. It could also be due to an increase i n f r i c t i o n generated by prolonged high speed work. This potential problem was I d e n t i f i e d p r i o r to data c o l l e c t i o n , thus care was taken to maintain the f r i c t i o n a l resistance constant throughout the tests. Additional measures including EMG of the upper body 86 might be useful to compare possible unmeasured muscle a c t i v i t y occurring during p o s i t i v e and negative work and during c y c l i n g at d i f f e r e n t pedalling frequencies. Such information would help to account for the performance of work extraneous to the experimental manipulation of int e r e s t . 87 CONCLUSIONS The conclusions from t h i s study are: 1) V02, HR, VE and VT were greater during p o s i t i v e than negative work at a constant power output of 60 Watts performed on a cycle ergometer. 2) The fb was comparable between p o s i t i v e and negative work at power output of 60 Watts. 3) At a power output of 60 Watts, a pedalling frequency of 75 rpm during p o s i t i v e work was more demanding p h y s i o l o g i c a l l y i n terms of V02, HR, VE and VT than 35"and 55 rpm. 4) At a power output of 60 Watts, a pedalling frequency of 75 rpm during negative work was more demanding p h y s i o l o g i c a l l y in terms of V02, HR, VE and VT than 55 rpm. 5) At a power output of 60 Watts, the slopes and intercepts of the regression l i n e s for the VE and V02, VT and VE, and fb and VE re l a t i o n s h i p s were comparable for p o s i t i v e and negative work. 6) At a power output of 60 Watts, the slopes of the regression l i n e s for the VE and V02 r e l a t i o n s h i p f o r p o s i t i v e and negative work were comparable while the intercept was aa higher for negative work. 7) High pedalling frequencies such as 75 rpm are ph y s i o l o g i c a l l y more demanding than lower pedalling frequencies such as 35 and 55 rpm. 8) The lower V02, HR and VE during negative work are consistent with higher e f f i c i e n c y when u t i l i z i n g predominately eccentric muscle contraction. 9) The higher VE during p o s i t i v e work could be explained by the higher VT because the fb was comparable for the two types of work. The r e s u l t i n g v e n t i l a t o r y response can be considered consistent with a Range 1 response. 10) The change i n VE from baseline to steady state for p o s i t i v e work was effected by increases i n VT and fb which i s consistent with a Range 1 response. 11) The change i n VE from baseline to steady state for negative work was predominantly effected by an increase in fb at pedalling frequencies at 35 and 55 rpm. At 75 rpm, an increase i n fb also contributed to the increase i n VE. This response i s not consistent with the Range 1 response. In summary, our data confirm and extend previous 89 work examining the ventilatory responses to negative work compared to p o s i t i v e work. On considering the e f f e c t of pedalling frequency on v e n t i l a t i o n , we concluded VE was determined primarily by a change i n VT because fb i s not s i g n i f i c a n t l y d i f f e r e n t among the three pedalling frequencies between the two types of work. 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Gross e f f i c i e n c y = work accomplished = W X 100% energy expended E Net e f f i c i e n c y = work accomplished = W X 100% energy expended above E - e that at rest Work e f f i c i e n c y = work accomplished = W X 100% energy expended above E i - Eu that i n c y c l i n g with-out a load Delta e f f i c i e n c y = delta work accomplished = W X 100% delta energy expended E where W = c a l o r i c equivalent of external work performed E = gross c a l o r i c output, including r e s t i n g metabolism e = res t i n g c a l o r i c output E i = c a l o r i c output, loaded c y c l i n g Eu = c a l o r i c output, unloaded c y c l i n g W = c a l o r i c equivalent of increment in work performed 103 above previous work rate E = Increment i n c a l o r i c output above that at previous work rate The above d e f i n i t i o n s of e f f i c i e n c y can be calculated using the t r a d i t i o n a l method (based on oxygen uptake and respiratory exchange r a t i o ) and the theoretical-thermodynamic method. Three assumptions (P/0 =3; G for ATP = -11 Kcal/mole; phosphorylative-coupling e f f i c i e n c y = 6054) have to be made when using the theoretical-thermodynamic method CWhipp et a l , 19693. The key difference among the e f f i c i e n c y d e f i n i t i o n s i s the sel e c t i o n of the baseline correction factor which changes the estimates of energy expenditure and as a r e s u l t the e f f i c i e n c y c a l c u l a t i o n . The theoretical-thermodynamic method, however, cannot be used to validate any one p a r t i c u l a r method of e f f i c i e n c y c a l c u l a t i o n because, i r r e s p e c t i v e of the method, the estimation of energy expended by the subject i s s t i l l obtained from oxygen consumption. When comparing the two methods, Gaesser and Brooks C19753 found no difference in the calculated e f f i c i e n c i e s i n two-thirds of the cases studied. In those that d i f f e r e d , the range of difference i n e f f i c i e n c i e s was between 0.2% -1.2%. The investigators concluded that since the t r a d i t i o n a l method considers the substrate u t i l i z e d during exercise i n the estimation of energy expenditure, t h i s method may y i e l d a more accurate measure of e f f i c i e n c y . 104 Of the four d e f i n i t i o n s of e f f i c i e n c y , work e f f i c i e n c y i s viewed to be t h e o r e t i c a l l y sound but d i f f i c u l t to obtain depending on the ergometer used. Delta e f f i c i e n c y i s considered to be the most p r a c t i c a l estimate of muscle e f f i c i e n c y . However, as pointed out by Hesser et a l C19773, in c a l c u l a t i o n s of both work and delta e f f i c i e n c y , unmeasured work at rest i s ignored. Stainsby et a l [19803 stated that when baseline subtraction was used in c a l c u l a t i n g e f f i c i e n c y , the v a l i d i t y depended on whether the baseline remained constant even at d i f f e r e n t work rates. In most a c t i v i t i e s studied, the baseline energy consumption varied d i r e c t l y with work rate. Hence the investigators cautioned against the use of baseline subtraction and promoted q u a n t i f i c a t i o n and description of the determinants of energy expenditure. 105 APPENDIX B The Contribution of Internal Work to Total Work Performed Winter t19793 defined i n t e r n a l work as "work involving a l l p o t e n t i a l and k i n e t i c energy components, a l l exchange of energy within and between segments, and both p o s i t i v e and negative work done by the muscle". Since the numerator of the e f f i c i e n c y formula ignored the i n t e r n a l work done by the body, common every day a c t i v i t i e s such as l e v e l walking w i l l have a zero e f f i c i e n c y and thus t h i s formula i s inadequate in measuring e f f i c i e n c y of human a c t i v i t i e s . With the i n c l u s i o n of i n t e r n a l work into the c a l c u l a t i o n of e f f i c i e n c y , more meaningful and consistent e f f i c i e n c y estimates can then be made. Wells et a l C19863 i n t h e i r study on concentric and eccentric c y c l i n g defined i n t e r n a l work as the work component required to r a i s e and lower the limbs and to change t h e i r v e l o c i t y . They measured i n t e r n a l work by d i r e c t l y using an eccentric cycle ergometer and calculated i n t e r n a l work from segmental energy changes using cinematography. They found no s i g n i f i c a n t difference between the two approaches. The mean in t e r n a l work rates (power output) obtained at pedal frequencies of 30, 60, 90 per minute were 11.5, 20, 62 W respectively. When the i n t e r n a l work rate was added to a p o s i t i v e external work rate (ie. concentric cy c l i n g ) , the 106 algebraic sum of t o t a l work rate was increased. When the same procedure was applied to a negative external work rate (ie. eccentric c y c l i n g ) , the algebraic sum of t o t a l work rate was decreased. Wells et a l therefore concluded that previous investigators had over-estimated the amount of negative work and underestimated the amount of p o s i t i v e work that was done by the musculature. Hence, the huge difference in e f f i c i e n c y reported previously between p o s i t i v e work and negative work i s reduced when i n t e r n a l work i s added to the numerator. In summary i n t e r n a l work tends to be ignored during e f f i c i e n c y c a l c u l a t i o n . This leads to inaccurate e f f i c i e n c y values e s p e c i a l l y at high pedalling frequencies and low work rates. This f i n d i n g therefore challenges the various e f f i c i e n c y values reported previously i n the l i t e r a t u r e . 107 APPENDIX C Borg's Scales of Subjective Perceived Exertion and Breathlessness during P o s i t i v e and Negative Work with Special Reference to Patients with Cardiorespiratory Disease. Many perceived exertion scales have been used to quantify subjective perception of exertion and thereby correlate t h i s sensation to physiological responses CBorg, 1970; Borg, 1982; Jones et a l , 1985; K i l l i a n et a l , 1985; Leblanc et a l , 1986; Mihevic, 1981; Silverman et a l , 1988; Stubbing et a l , 19833. However, Borg scales have been reported to be superior to others [Jones et a l , 1985; Mihevic, 1981; Silverman et a l , 1988 3. Mihevic [19813 concluded that multiple sensory inputs of l o c a l and central o r i g i n were integrated by the brain and gave r i s e to the subjective perception of exertion. This notion was supported by subsequent studies on exercise and v e n t i l a t i o n i n normal subjects and patients with lung disease [Jones et a l , 1985; Leblanc et a l , 1986; Stubbing et a l , 1983; Silverman et a l , 19883. Borg's [1970, 1982 3 rating of perceived exertion <RPE) i s an ordinal scale consisting of 15 points ranging from 6 to 20. Descriptive terms such as "very l i g h t " , "hard", "very hard", are l i s t e d beside the odd numbers. Borg [19823 advocated the use of t h i s scale to measure perceived exertion during exercise t e s t i n g i n patient as well as healthy populations. He 108 concluded that RPE i s correlated with heart rate and blood l a c t a t e during exercise. These scales are p o t e n t i a l l y useful in monitoring the exertion of ILD patients because they have the same a b i l i t y to detect added r e s i s t i v e or e l a s t i c loads as normal subjects CBurki et a l , 1985]. Silverman et a l [1988] reported that RPE was highly r e l i a b l e and correlated well with physiological variables such as VE, HR, and V02 during exercise of obstructive lung disease patients. These investigators found that RPE was more reproducible in repeated t e s t i n g than physiological variables. More recently, Borg [1982] proposed a modified scale with r a t i o properties. This scale ranged from 0-10 with descriptive terms such as "very weak", "strong", "very strong". Borg [1982] advocated t h i s scale for assessing breathing d i f f i c u l t y and general discomfort during exercise. Jones et a l [1985] reported perceived respiratory e f f o r t using t h i s new scale was highly related to mouth pressure, i n s p i r a t o r y time and breathing frequency. Leblanc et a l [1986] used t h i s new scale to measure breathlessness i n patients with cardiorespiratory disease. These investigators reported that breathlessness was related to respiratory muscle e f f o r t such as the sum of duty cycle, breathing frequency and i n s p i r a t o r y flow rate. Harver et a l 11988] used t h i s scale to evaluate breathlessness i n ILD patients and normal subjects during progressive exercise tests. They found that Borg scores (0-10) were related l i n e a r l y to minute v e n t i l a t i o n i n both groups of subjects, however, the 109 slope of the regression l i n e was steeper i n the ILD patients than normal subjects. K i l l i a n [1987] reported that breathlessness was inversely related to ve n t i l a t o r y capacity and inspiratory muscle strength. But, subjects with impaired v e n t i l a t o r y capacity and healthy subjects terminated exercise at s i m i l a r l e v e l s of breathlessness as assessed by Borg's scale [ K i l l i a n , 19873. In summary, both scales proposed by Borg [1970, 1982] have sound physiological bases and good measurement r e l i a b i l i t y . These scales correlated well with changes i n phy s i o l o g i c a l parameters during exercise i n patients with cardiorespiratory disease and also showed good measurement r e p r o d u c i b i l i t y . 110 APPENDIX D The Exercise Responses of Two Patients with I n t e r s t i t i a l Lung Disease to P o s i t i v e and Negative Work Performed on a- Cycle Ergometer. A Case Report. INTRODUCTION I General Purpose In the r e h a b i l i t a t i o n of disabled and/or older subjects, endurance t r a i n i n g and e f f i c i e n t use of energy are treatment p r i o r i t i e s . Although t r a d i t i o n a l approaches to improve endurance, strength and power may have demonstrable therapeutic value CLertzman and Cherniak, 1976; Cockcroft et a l , 1981; Komi, 19863, l i t t l e information, i f any, i s available on optimizing energy u t i l i z a t i o n i n patients with chronic disease. We propose that the effectiveness of t r a d i t i o n a l endurance programs could be enhanced by incorporating parameters of exercise whereby the patient can conserve energy yet e f f e c t i v e l y perform a greater amount of work. Negative work (eccentric exercise) and rate at which work i s performed are two examples of exercise parameters that could enhance the functional work capacity of patients with reduced physiologic reserves. I l l I n t e r s t i t i a l lung disease (ILD) i s a serious lung a f f l i c t i o n which l i k e chronic obstructive airway disease (COAD), can lead to severe functional impairment, morbidity and mortality. Limitations of the e x i s t i n g l i t e r a t u r e have hindered the characterization of the cardiorespiratory responses of ILD patients at rest and during exercise [Chung and Dean, 1989]. Given that symptoms of cardiorespiratory disease become more problematic f o r patients during physical stress than at rest, exercise t e s t i n g can be considered an e s s e n t i a l component of the c l i n i c a l evaluation. However, the acute and e s p e c i a l l y long term exercise responses of ILD patients have not been well studied. The paucity of such information has hampered advances i n the long term management of ILD and r e h a b i l i t a t i o n of patients with these diseases. The focus of t h i s preliminary investigation, therefore, was to examine negative work and pedalling frequency (speed) as parameters that could be used to optimize e f f i c i e n c y during exercise using cycle ergometer. Furthermore, the use of negative work and " e f f i c i e n t " pedalling speed might enable ILD patient to take part i n active exercise programs with l e s s s t r a i n on the cardiorespiratory system and at lower energy cost. However, t h i s hypothesis needs to be further tested. 112 II Etiology and Prevalence of ILD Various e t i o l o g i c a l factors are responsible for i n t e r s t i t i a l lung disease (ILD). ILD i s comprised of over 130 diseases such as pneumoconiosis, e x t r i n s i c a l l e r g i c a l v e o l i t i s , sarcoidosis and chronic f i b r o s i s CDemeter, 1986; Lenfant, 19801. The disease can be l o c a l i z e d , eg, lung abscess or suppurative pneumonitis, or diffuse, eg, inhalation of organic dusts or toxic fumes CCherniack and Cherniack, 1983]. Various l i v e r disorders, c i g a r e t t e smoking and a genetic predisposition can also lead to f i b r o t i c lung disease CHammer, 1987]. No apparent cause, however, can be i d e n t i f i e d i n the majority of patients with ILD CHammar, 1987; Lenfant, 1980]. Sharma and Balchum [1983] reported various causes of ILD and t h e i r r e l a t i v e incidence. To summarize, f i b r o s i s of the lung can r e s u l t from b a c t e r i a l , v i r a l and fungal infect i o n s . In addition, lung f i b r o s i s may be associated with rheumatoid and collagen diseases such as rheumatoid a r t h r i t i s and systemic lupus erythmatosis. One to 9X of farming populations and 6-15% of pigeon breeders are a f f l i c t e d with ILD. Several years ago, a National I n s t i t u t e of Health task force attempted to characterize the epidemiologic features of ILD [Lenfant, 1980]. Explanations for the epidemiological c h a r a c t e r i s t i c s of ILD, however, have yet to be i d e n t i f i e d . Based on prevalence s t a t i s t i c s for ILD, t h i s task force projected hospital admissions for patients with nine of the most common 113 i n t e r s t i t i a l lung diseases (eg. pulmonary sarcoidosis and asbestosis) in 1977 i n the United States to be 142,500 [Lenfant, 19803. For the same period, the projected number of hospital admissions for asthma patients was 32,000 [Lenfant, 19803. I l l Pathophysiology and C l i n i c a l features of ILD Approximately f o r t y years ago, Austrian et a l [19513 coined the term " a l v e o l a r - c a p i l l a r y block" to describe a r t e r i a l hypoxemia i n patients with f i b r o t i c lung disease. Later, however, Finley et a l [19623 suggested that the alveolar-c a p i l l a r y membrane i n i n t e r s t i t i a l pulmonary disease was affected i n a non-uniform manner leading to v e n t i l a t i o n and perfusion (VA/Q) mismatch, and consequently, a r t e r i a l hypoxemia. More recently, VA/O mismatch has been reported to be the source of hypoxemia at re s t i n both mild and advanced f i b r o t i c lung disease [Jernudd-Wilhelmsson, 1986; Spiro et a l , 19813. I n t e r s t i t i a l lung disease i s characterized by inflammation of the lung parenchyma which may resolve completely or progress to f i b r o s i s [Snider, 19863. I n t e r s t i t i a l pulmonary f i b r o s i s (IPF) r e f e r s to the l a t t e r , i e , f i b r o s i s r e s u l t i n g from inflammation of the lung parenchyma which leads to the deposition of excess connective tissue. Because some ILD patients recover completely while others progress to chronic 114 f i b r o s i s tJernudd-Wilhelmsson, 1986], Snider [1986] considered IPF a subset of ILD. IPF can be subdivided into granulomatous or nongranulomatous types. Some common diagnoses associated with IPF are shown in the Figure. Although patients with ILD form a heterogeneous group with respect to disease etiology, they share some s i m i l a r c l i n i c a l , r a d i o l o g i c a l , physiological, and pathological features. Finucane and Prichard [1984] reported ILD patients have abnormalities i n alveolar function consistent with morphological changes of i n t e r s t i t i a l i n f i l t r a t i o n and f i b r o s i s , i n t r a - a l v e o l a r exudate and alveolar replacement. Functionally, these abnormalities can lead to reduced lung volume, increased expiratory flow at mid lung volume and decreased lung d i s t e n s i b i l i t y , i e , a reduced lung volume change f o r a given pressure change [Finucane et a l , 1984; Renzi et a l , 1986; Risk et a l , 1984; Spiro et a l , 1981]. The c h a r a c t e r i s t i c s h i f t of the pressure-volume curve (down and to the right) [Bates et a l , 19893 r e f l e c t s increased lung e l a s t i c i t y i n ILD which r e s i s t s lung expansion CWeitzenblum et a l , 1983; Whipp and Pardy, 1986; Winterbauer and Hutchison, 1980]. Patients with ILD, however, t y p i c a l l y have n e g l i g i b l e a i r flow obstruction [Athos et al,1986; Perez-Padilla et a l , 1985]. The d i f f u s i o n capacity for carbon monoxide (DLCO) i s decreased and a r t e r i a l blood gas analysis may reveal hypoxemia i n the absence of hypercapnia [Huang et a l , 1979; Snider, 1986]. These patients commonly complain of shortness of breath on exertion 115 CBurdon et a l , 1983] and, i n severe cases, at rest. This l i m i t a t i o n can terminate a patient's g a i n f u l employment and severely compromise the qual i t y of the patient's l i f e . Physiologic predictors of exercise l i m i t a t i o n i n patients with ILD are summarized i n Table I. A decrease i n DLCO [Anderson and Bye, 1984; Athos et a l , 1986; Cotes et a l , 1988; Finucane and Prichard, 1984; Risk et a l , 1982b; Shaw and Kataria, 1982; Winterbauer and Hutchison, 1980] and reduced pulmonary function measures [Athos et a l , 1986; Bye et a l , 1982; Cotes et a l , 1988; Finucane et a l , 1984; Markos et a l , 1988; Shaw and Kataria, 1982] have received the most support for predictors of abnormal exercise response, eg, a r t e r i a l oxygen desaturation. However, Cotes et a l [1988] reported when minute v e n t i l a t i o n at oxygen uptake of 1 1/min during exercise was considered along with r e s t i n g pulmonary function measures, the prediction of exercise l i m i t a t i o n i n ILD patients s i g n i f i c a n t l y improved. The causes of morbidity and mortality of patients with ILD vary according to the s p e c i f i c underlying pathophysiology. In general, functional impairment has been reported to be least i n patients with sarcoidosis and e x t r i n s i c a l l e r g i c a l v e o l i t i s ; and most severe i n idi o p a t h i c pulmonary f i b r o s i s [Markos et a l , 1988; McNicholas et a l , 1986 Spiro et a l , 1981; Weitzenblum et a l , 1983]. 116 IV Physiologic Responses of ILD Patients at Rest The e f f e c t of sleep on a r t e r i a l desaturation i n patients with ILD i s controversial. Oxygen desaturation during sleep has been reported i n some ILD patients e s p e c i a l l y during periods of snoring and REM sleep [Bye et a l , 1984; McNicholas et a l , 1986; Midgren et a l , 1987; Perez-Padilla et a l , 1985]. However, others [McNicholas et a l , 1986; Midgren et a l , 1987] reported l i t t l e change i n oxygen saturation between wakefulness and sleep i n these patients. The discrepencies among studies could be explained by the presence of sleep disturbances i n those subjects. Thus nocturnal oxygen therapy does not appear to be necessary i n those patients who have acceptable Pa02 l e v e l s when awake [McNicholas et a l , 1986]. Table II summarizes the cardiorespiratory function of ILD patients during an awake r e s t f u l state. In general, ILD patients have varying degrees of pulmonary and cardiovascular abnormalities at rest. Minute v e n t i l a t i o n at rest tends to be normal or elevated [Dimarco et a l , 1983; Leblanc et a l , 1986; Lupi-Herrera et a l , 1985; Renzi et a l , 1986; Spiro et a l , 1981] while the breathing pattern i s rapid and shallow [Jernudd-Wilhelmsson et a l , 1986; Renzi et a l , 1986; Spiro et a l , 1981]. The v e n t i l a t o r y dead space per breath and the oxygen consumption at rest are also elevated [Jernudd-Wilhelmsson et a l , 1986]. Some ILD patients have decreased Pa02 at rest while PaC02 tend to be decreased [Huang et a l , 1979]. Resting heart 117 rate tends to be elevated CSpiro et al,1981; Wasserman et a l , 19793. Pulmonary vascular resistance and pressure are also increased at rest while pulmonary c a p i l l a r y wedge pressure and mean systemic blood pressure are comparable to the healthy population [Hawrylkiewicz et a l , 1982; Jernudd-Wilhelmsson et a l , 1986; Lupi-Herrera et a l , 1985; Sturani et a l , 1986; Wasserman et a l , 1979; Weitzenblum et a l , 19833. V Physiologic Responses of ILD Patients at Submaximal Exercise Table III summarizes the cardiorespiratory responses of ILD patients to submaximal exercise. Several investigators CArita et a l , 1981; Anderson et a l , 1984; Burdon et a l , 1983; Jernudd-Wilhelmsson et a l , 1986; Lupi-Herrera et a l , 1985; Herrhaeghe et a l , 19813 have reported that minute v e n t i l a t i o n i s markedly increased i n r e l a t i o n to V02 i n patients with ILD, even at very low work rates. This increase was effected by an increase i n the breathing frequency and a decrease i n t i d a l volume compared with normal subjects [Anderson and Bye, 1984; Bradley and Crawford, 1976; Bye et a l , 1982; Dimarco et a l , 1983; Jones and Rebuck, 1979; Meerhaeghe et a l , 1981; Spiro et a l , 19813. Meerhaeghe et a l [19813 suggested t h i s breathing pattern r e f l e c t e d the use of a lower peak and t o t a l i nspiratory muscle force which may e f f e c t i v e l y delay the onset of respiratory 118 muscle fatigue. Renzi et a l [1986 3 observed increased VD/VT in exercising ILD patients and attributed i t to the reduced t i d a l volume, increased breathing frequency and increased lung e l a s t i c i t y . Furthermore, an increased physiological dead space and VA/Q mismatch necessitated an increased v e n t i l a t i o n to remove carbon dioxide. Occlusion pressure [Hesser and Lind, 1983; M i l i c - E m i l i et a l , 19753, an index of the neural output of the respiratory center, was reported to be increased i n ILD patients [Meerhaeghe et a l , 1981; Renzi et a l , 1986 3. The increase i n respiratory drive may r e f l e c t increased afferent r e f l e x a c t i v i t y from the lung or chest wall [Meerhaeghe et a l , 1981; Renzi et a l , 19863. Some investigators [Aldrich et a l , 1982; Dimarco et a l , 19833 have concluded that neural mechanisms such as vagal stimulation and mechanoreceptor stimulation i n the chest wall increase respiratory drive and thereby a l t e r breathing pattern. The r e l a t i v e s i g n i f i c a n c e of these determinants of breathing pattern, however, i s unclear [Shannon, 1986 3. Patients with a low DLCO at rest tend to desaturate during exercise [Anderson and Bye, 1984; Risk et a l , 1982a3. Spiro et a l [19813 studied patients with f i b r o s i n g a l v e o l i t i s and sarcoidosis, and reported that at submaximal work rates heart rate was s i g n i f i c a n t l y increased, stroke volume was reduced and cardiac output was normal. The disproportionate increase in 119 submaximal exercise heart rate s i m i l a r to the resting tachycardia CSpiro et a l , 1981; Wasserman et a l , 1979] observed i n ILD patients may r e f l e c t reduced saturation or increased pulmonary artery pressure. However these explanations do not rul e out the e f f e c t of cardiorespiratory deconditioning i n patients with ILD. Cardiac hemodynamics can be compromised during exercise i n ILD patients iHawrylkiewicz et a l , 1982; Lupi-Herrera, 1985; Sturani et a l , 1986; Weitzenblum et a l , 1983]. Risk et a l [1982b] reported oxygen desaturation and decreased right v e n t r i c u l a r ejection f r a c t i o n i n severe ILD patients. The r i g h t v e n t r i c u l a r dysfunction, d i r e c t l y related to the severity of exercise-induced hypoxemia, was observed only during exercise and was reversed when patients breathed 100% oxygen [Hawrylkiewicz et a l , 1982; Risk et a l , 1982b]. Increased r i g h t v e n t r i c u l a r work i n ILD patients has also been reported [Sturani et a l , 1986]. In summary, rapid shallow breathing i s prevalent i n ILD patients during submaximal exercise. The degree of oxygen desaturation observed depends on the severity of the disease. The v e n t i l a t o r y drive i s apparently increased with an increase i n VD/VT and no change i n Ti/Ttot. Pulmonary vascular resistance may increase r e s u l t i n g i n increased r i g h t v e n t r i c u l a r work. 120 VI Rationale f o r P i l o t Study Young a t h l e t i c subjects have been t y p i c a l l y used i n the l i t e r a t u r e to study physiologic responses using negative work and to study the e f f e c t s of pedalling frequency. We are interested in the potential therapeutic benefit of energy-e f f i c i e n t negative work i n the management of i n d i v i d u a l s with cardiorespiratory l i m i t a t i o n , such as i n d i v i d u a l s with i n t e r s t i t i a l lung disease. We were p a r t i c u l a r l y interested i n determining the e f f e c t of negative work on in d i v i d u a l s with ILD given that our work has shown negative work e l i c i t s a rapid shallow breathing response which i s the t y p i c a l response of these i n d i v i d u a l s to exercise. In addition, i t i s not known whether the i n d i v i d u a l with ILD who tends to be older could harness the potential energy stored i n the serie s e l a s t i c component during negative work as e f f e c t i v e l y as younger a t h l e t i c subjects. This p i l o t study was therefore designed to look at the oxygen consumption, heart rate and the ve n t i l a t o r y responses of two ILD subjects during p o s i t i v e and negative work at 35, 55 and 75 rpm at a work rate of 60 Watts. The r e s u l t s of t h i s preliminary work w i l l provide the basis f o r future large scale studies. 121 VII Study Questions 1) To compare V02, HR, VE, VT and fb of ILD subjects between po s i t i v e and negative work. 2) To examine the e f f e c t of pedalling frequency on V02, HR and VE i n ILD subjects. 3) To compare i n a general way the exercise responses of ILD subjects to those of healthy middle-aged men. 122 Figure Schematic c l a s s i f i c a t i o n of i n t e r s t i t i a l pulmonary f i b r o s i s with common diagnosis i n each category. Interstitial Pulmonary Fibrosis 1 Granulomatosis 1 1 Nongranulomatosis | Known Etiology Unknown Etiology Known Etiology Unknown Etiology Asbestosis, Silicosis Sarcoidosis Idiopathic IPF, Fibrosis Alveolitis > 123 Hypersensitivity pneumonia T A B L E I PREDICTORS OF EXERCISE LIMITATION IN PATIENTS WITH ILD. ADAPTED FROM CHUNG AND DEAN [1989]. P R E D I C T O R R E F E R E N C E S 1) Increased r e s t i n g P<A-a>02 3,23 2) Decreased DLCO 3,6,8,11,23, 25, 30 3) Reduced pulmonary function 3,6,8,11,25 (eg.TLC, FVC, FEV1) 4) Severity of chest X-ray findings 3 5) VE at V02 of 1.0 1/min 8 P(A-a)02 - difference i n oxygen p a r t i a l pressure between alveolar space and a r t e r i a l blood DLCO - index of d i f f u s i n g capacity of the lung using carbon monoxide TLC - t o t a l lung capacity FVC - forced v i t a l capacity FEVi - forced expiratory volume i n one second VE - minute v e n t i l a t i o n V02 - oxygen consumption 124 TABLE II RESTING CARDIORESPIRATORY PARAMETERS OF ILD PATIENTS COMPARED TO NORMAL SUBJECTS. ADAPTED FROM CHUNG AND DEAN [19893. RESPIRATORY PARAMETER RESPONSE REFERENCES VE RR Tida l volume V02, VD/VT Pa02 PaC02 Occlusion pressure no change, increased increased decreased increased no change, decreased decreased increased 6, 10, 15, 17, 18, 22 5, 15, 22 5, 22 15 6, 10-14,29 10, 12, 13 10, 18 CARDIOVASCULAR PARAMETER RESPONSE REFERENCES Heart rate increased 26,28 PCWP no change 13,27,29 PVR increased 13,15,18,27,28 PAP increased 13,15,18,27-29 Mean systemic BP no change 15 Cardiac Output normal, decreased 15, 21 VE - minute v e n t i l a t i o n RR - respiratory rate VD/VT - the ve n t i l a t o r y dead space per breath Pa02 - a r t e r i a l oxygen p a r t i a l pressure PaC02 - p a r t i a l pressure of a r t e r i a l carbon dioxide Occlusion pressure - an index of ce n t r a l respiratory drive PCWP - pulmonary c a p i l l a r y wedge pressure i s an index of l e f t heart function PVR - pulmonary vascular resistance PAP - pulmonary a r t e r i a l pressure BP - blood pressure 125 TABLE III CARDIORESPIRATORY RESPONSES OF ILD PATIENTS COMPARED TO NORMAL SUBJECTS DURING SUBMAXIMAL EXERCISE. ADAPTED FROM CHUNG AND DEAN [1989 3. RESPIRATORY PARAMETER RESPONSE REFERENCES VE/V02 RR Tidal volume Duty cycle (Ti/Ttot) T i , Ttot VD/VT V/Q mismatch Pa02 Occlusion pressure increased increased decreased no change or decrease decreased increased increased decreased increased 1, 2, 5, 6, 15, 18, 20 1,4,4, 10, 15, 16, 19, 20, 26 1, 4,5, 10, 16,26 4, 5, 20 4,5,10 2, 3,9, 11, 22 11, 15, 22 1, 3, 15, 23, 24, 29 26, 29 CARDIOVASCULAR PARAMETER RESPONSE REFERENCES Heart rate Stroke volume Right v e n t r i c u l a r ejection f r a c t i o n PAP PVR Cardiac output RVSWI increased, decreased, decreased increased increased decreased, increased no change no change no change 5, 26 18, 26 24 13, 27 27, 29 11, 18, 26 27 VE/V02 - ve n t i l a t o r y equivalent f o r oxygen Duty cycle - in s p i r a t o r y duration <Ti) divided by the sum of insp i r a t o r y duration and expiratory duration Ttot - sum of in s p i r a t o r y duration and expiratory duration V/Q - vent i l a t i o n - p e r f u s i o n r a t i o RVSWI - r i g h t v e n t r i c u l a r stroke work index 126 TABLE IV REFERENCES FOR TABLES I-III 1. Anderson SD, Bye PTP. Exercise t e s t i n g in the evaluation of d i f f u s e i n t e r s t i t i a l lung disease. Aust NZ J Med Suppl 14(3)-.763-768, 1984 2. A r i t a KI, Nishida 0, Hiramoto T et a l : Physical exercise i n "pulmonary f i b r o s i s " . Hiroshima J Med Sci 30:149-159, 1981 3. Athos L, Mohler JG, Sharma OP: Exercise t e s t i n g in the physiologic assessment of sarcoidosis. Ann NY Acad S c i 465:491-500, 1986 4. Bradley GW, Crawford R: Regulation of breathing during exercise i n normal subjects and i n chronic lung disease. Cl Sci Mol Med 51:575-582, 1976 5. Burdon JGW, K i l l i a n KJ, Jones NL: Pattern of breathing during exercise i n patients with i n t e r s t i t i a l lung disease. Thorax 38:778-784, 1983 6. Bye PTP, Anderson SD, Woolcock AJ et a l : Bicycle endurance performance of patients with i n t e r s t i t i a l lung disease breathing a i r and oxygen. Am Rev Respir Dis 126:1005-1012, 1982 7. Cotes JE: Exercise testing. In: Lung biology i n health and disease. Occupation Lung Disease, Lenfant C (Ed). New York, NY, Marcel Dekker, Vol 18, pp 99-122, 1981 8. Cotes JE, Zejda J, King B: Lung function impairment as a guide to exercise l i m i t a t i o n i n work-related lung disorders. Am Rev Respir Dis 137:1089-1093, 1988 9. D'Alonzo G, Bower J, Crevey B et a l : Gas exchange a l t e r a t i o n during exercise i n patients with pulmonary hypertension. Am Rev Respir Dis Suppl 125:86, 1982 10. Dimarco AF, Kelsen SG, Cherniack NS et a l : Occlusion pressure and breathing pattern i n patients with i n t e r s t i t i a l lung disease. Am Rev Respir Dis 127:425-430, 1983 11. Finucane KE, Prichard MG: Lung function i n f i b r o s i n g a l v e o l i t i s . Aust NZ J Med Suppl 14(3):749-754, 1984 12. Gallagher CG, Younes M: Breathing pattern during and after maximal exercise i n patients with chronic obstructive lung disease, i n t e r s t i t i a l lung disease, and cardiac disease, and i n normal subjects. Am Rev Respir Dis 133:581-586, 1986 13. Hawrylkiewicz I, Izdebska-Makosa Z, Grebska E et a l : Pulmonary hemodynamics at rest and on exercise i n patients 127 with i d i o p a t h i c pulmonary f i b r o s i s . B u l l Europ Physiopath Resp 18:403-410, 1982 14. Huang CT, Heurich AE, Rosen Y et a l : Pulmonary sarcoidosis. Roentgenographic, functional, and pathological correlations. Respiration 37:337-345, 1979 15. Jernudd-Wilhelmsson Y, Hornblad Y, Hedenstierna G: Ven t i l a t i o n perfusion r e l a t i o n s h i p s in i n t e r s t i t i a l lung disease. Eur J Respir Dis 68:39-49, 1986 16. Jones NL, Rebuck AS: Ti d a l volume during exercise i n patients with d i f f u s e f i b r o s i n g a l v e o l i t i s . B u l l Eur Physiopathol Respir 15:321-327, 1979 17. Leblanc P, Bowie DM, Summer et a l : Breathlessness and exercise i n patients with cardiorespiratory disease. Am Rev Respir Dis 133:21-25, 1986 18. Lupi-Herrera E, Seoane M, Verdejo J et a l : Hemodynamic e f f e c t of hydralazine i n i n t e r s t i t i a l lung disease patients with cor pulmonale. Chest 87:565-573, 1985 19. Mathews JI, Hooper RG: Exercise t e s t i n g i n pulmonary sarcoidosis. Chest 83:75-81, 1983 20. Meerhaeghe AV, Scano G, Sergysels R et a l : Respiratory drive and ve n t i l a t o r y pattern during exercise i n i n t e r s t i t i a l lung disease. B u l l Europ Physiopath Resp 17:15-26, 1981 21. M i l l e r MJ, Chappell TR, Cook W et a l : E f f e c t s of o r a l hydralazine on gas exchange i n patients with cor pulmonale. Am J Med 75:937-942, 1983 22. Renzi G, M i l i c - E m i l i J, Grassino AE: Breathing pattern i n sarcoidosis and idi o p a t h i c pulmonary f i b r o s i s . Ann NY Acad Sci 465:482-490, 1986 23. Risk C, Epler GR, S i c i l i a n L. Exercise a l v e o l a r - a r t e r i a l oxygen pressure difference i n i n t e r s t i t i a l lung disease. Am Rev Respir Dis Suppl 125:258, 1982 24. Risk C, Rothendler JA, Epler GR et a l : Right v e n t r i c l e performance during exercise i n i n t e r s t i t i a l lung disease. Am Rev Respir Dis Suppl 125:104, 1982 25. Shaw RA, Kataria YP: Pulmonary function test i n patients with sarcoidosis. Am Rev Respir Dis Suppl 125:123, 1982 26. Spiro SG, Dowdeswell IRG, Clark TJH: An analysis of submaximal exercise responses i n patients with sarcoidosis and f i b r o s i n g a l v e o l i t i s . Br J Dis Chest 75:169-180, 1981 128 27. Sturani C, Spyridion P, Galavotti V et a l : Pulmonary vascular responsiveness at rest and during exercise i n idio p a t h i c pulmonary f i b r o s i s : e f f e c t s of oxygen and nifedipine. Respiration 50:117-129, 1986 28. Wasserman KL, Whipp BJ, Casaburi R et a l : Ventilatory control during exercise in man. Bull Europ Physiopath Respir 15:27-47, 1979 29. Weitzenblum E, Ehrhart M, Rasaholinjanahary J et a l . Pulmonary hemodynamics i n idi o p a t h i c pulmonary f i b r o s i s and other i n t e r s t i t i a l pulmonary diseases. Respiration 44:118-127, 1983 30. Winterbauer RH, Hutchison JF: Use of pulmonary function t e s t s i n the management of sarcoidosis. Chest 78:640-647, 1980 129 MEJHQDS The research design, equipment and measures, and general procedures are described on pages 30 to 39. The i n c l u s i o n c r i t e r i a f o r the ILD subjects into t h i s p i l o t study were: (1) a c l i n i c a l course consistent with i n t e r s t i t i a l lung disease; <2) chest radiographs c h a r a c t e r i s t i c of i n t e r s t i t i a l lung disease; (3) forced v i t a l capacity between 45 to 75% of the predicted value <4> absence of c l i n i c a l or spirometric evidence of airflow obstruction (FEV1/FVC>75% of predicted), ischaemic heart disease, or other conditions a f f e c t i n g exercise capacity. Individual data are presented for the two ILD subjects studied. Some general comparisons of the responses of these subjects to those of the healthy middle-aged male subjects studied i n the t h e s i s are presented. 130 RESULTS SUBJECT CHARACTERISTICS The two ILD subjects, J.H., a 71 yr old man and M.H., a 64 yr old woman, were older than the mean age of the healthy subjects studied i n the thesis. The BHIs for both ILD subjects were also higher than the healthy subjects. The r e s u l t s of the pulmonary function t e s t s are summarized i n Table V. J.H. had a more severe r e s t r i c t i v e pattern of lung disease with a FVC that was 50% of predicted. M.H. showed mild to moderate r e s t r i c t i v e pattern with a FVC that was 61% of predicted. Their FEV1/FVC r a t i o s showed no sign of airway obstruction and were higher than predicted which i s consistent with a r e s t r i c t i v e pattern of lung disease. J.H. had moderately severe lung dysfunction and had to terminate the p o s i t i v e work te s t s between 2.5 to 3 minute of steady rate exercise due to shortness of breath. During the negative work tests, J.H. completed 4 minutes of steady rate exercise. The data presented for J.H. were therefore the test r e s u l t s at the l a s t minute of steady rate exercise. M.H. was able to complete f i v e minutes of steady-rate c y c l i n g during both p o s i t i v e and negative work as required. J.H. had a Sa02 of 94.5% at rest and showed 131 desat.urat.ion during p o s i t i v e work to about 90% at 35 and 75 rpm and 93% at 55 rpm. During negative work, the Sa02 remained at 94% for the four minutes of steady-rate cycling. In contrast, M. H. had a Sa02 of 96% at rest and remained stable during cycli n g i n both types of work. J.H. reported a breathlessness score of 4.0 and 1.75 using Borg's scale during p o s i t i v e and negative work respectively. M.H. reported a breathlessness score of 0. 75 and 0.0 using Borg's scale during p o s i t i v e and negative work respectively. The raw data f o r V02, HR, VE, VT and fb f o r the two ILD subjects during steady rate p o s i t i v e and negative work are shown i n Table V. OXYGEN CONSUMPTION The V02 f o r the two subjects during both p o s i t i v e and negative work generally followed the same trend as healthy middle aged men. J.H. who had r e l a t i v e l y severe r e s t r i c t i v e lung function had a V02 close to one standard deviation above that f o r healthy subjects during p o s i t i v e work. M.H. who had mild to moderate r e s t r i c t i v e lung function had a V02 close to the mean value f o r healthy subjects. In negative work, both subjects had a V02 close to the mean value for healthy subjects. 132 HEART RATE J.H. had a heart rate response s i m i l a r to the healthy subjects while M.H. has a higher heart rate response than healthy subjects. The trend was generally comparable to healthy subjects. MINUTE VENTILATION Minute v e n t i l a t i o n tended to be higher f o r both subjects during p o s i t i v e work. For example, J.H. had a VE greater than one standard deviation above the mean for healthy subjects at 75 rpm during p o s i t i v e work. In contrast, during negative work the VE tended to be closer to the mean VE of healthy subjects for both ILD subjects. The VE was comparable to the healthy subjects during p o s i t i v e and negative work. TIDAL VOLUME The t i d a l volume tended to be smaller for M.H. while VT for J.H. was close to the mean value f o r the healthy subjects. The VT response tended to follow the same trend as the healthy subjects during p o s i t i v e and negative work. 133 BREATHING FREQUENCY The breathing frequency tended to be higher i n both subjects and was greater than one standard deviation above the mean for the healthy subjects, during the more demanding po s i t i v e work. During negative work, the breathing frequency fo r both ILD subjects was closer to the mean value for healthy subjects. 134 TABLE V RESULTS OF PULMONARY FUNCTION TESTS AND ANTHROPEMETRIC DATA OF ILD SUBJECTS SUBJECT SEX AGE WEIGHT HEIGHT BMI (years) (kg) (cm) (kg/m.m) J.H. Male 71 111.1 189.® 31.1 M.H. Female 64 86.2 173.0 28.8 FEV1 FEV1 y. FVC FVC% RATIO RATIO'/. (1) C/.) (1) C/.) (7.) C/.) 1.98 60 2.48 50 80.0 119 1.80 72 2.08 61 86.5 119 135 T A B L E V I SUMMARY OF EXERCISE TEST RESULTS OF TWO ILD SUBJECTS POSITIVE WORK NEGATIVE WORK <rpm) (rpm) VARIABLE SUBJECT 35 55 75 35 55 75 V02 M.H. .94 .96 (1/min) J.H. 1.28 1.29 V02 M.H. 10.9 11.1 (ml/kg/min) J.H. 11.5 11.6 HR M.H. 122.8 123.2 (bpm) J.H. 100.1 99.4 VE M.H. 30.5 27.5 (1/min) J.H. 36.2 41.8 VT M.H. 1.13 1.11 (1/br) J.H. 1.35 1.52 fb M.H. 27.0 24.8 (br/min) J.H. 26.8 27.5 .98 .47 .43 .57 I. 32 .49 .52 .55 II. 4 5.5 5.0 6.6 11.8 4.4 4.7 5.0 125.6 89.8 85.8 96.7 103.2 69.8 71.1 72.5 32.4 13.7 12.4 17.8 39.7 15.4 17.3 18.3 1.16 .75 .69 .83 1.64 .80 .85 .82 27.9 18.3 17.9 21.5 24.2 19.3 20.4 22.0 136 DISCUSSION I E f f e c t s of Cycle Ergometry on Oxygen Consumption In general, the exercise responses of two ILD subjects followed the same general trend as the middle-aged healthy subjects studied i n the thesis. J.H. who had r e l a t i v e l y severe lung disease had a greater V02 and VE during p o s i t i v e work. The increase i n VE could be due to i n e f f i c i e n t gas exchange while the increase i n V02 could be p a r t i a l l y due to increased oxygen cost to operate the vent i l a t o r y pump. During negative work, V02 and VE for both subjects were s i m i l a r to the mean V02 and VE for the healthy subjects. II E f f e c t s of Cycle Ergometry on Heart Rate The ILD subjects reported a lower general a c t i v i t y l e v e l and greater p h y s i c i a l exertion i n performing a c t i v i t i e s of d a i l y l i v i n g than our healthy subjects. Thus we predicted these two in d i v i d u a l s to have a higher HR compared to the healthy subjects during rest and exercise CMcArdle et a l , 1986; Astrand and Rodahl, 19883. Indeed M.H. had an elevated HR response r e l a t i v e to the healthy subjects. However, J.H. had a lower heart rate response than expected and was comparable to the mean value f o r the healthy subjects. Investigation i n t o the heart rate response of J.H. had been i n i t i a t e d by the r e f e r r i n g physician. No apparent cause f o r t h i s heart rate 137 response had yet been forwarded. I l l E f f e c t s of Cycle Ergometry on Minute V e n t i l a t i o n and i t s Components The minute v e n t i l a t i o n of the two ILD subjects e s p e c i a l l y J.H. was greater than healthy subjects. This l i k e l y r e f l e c t e d a decrease i n the e f f i c i e n c y of the v e n t i l a t o r y pump [Whipp and Pardy, 19861. T i d a l volume during p o s i t i v e work was s i m i l a r to that of the healthy subjects. However the VT/FVCX was about 60% f o r J.H. and 54% f o r M.H. The breathing frequency was also higher than f o r the healthy subjects during p o s i t i v e work. This could be explained by the lower VC i n the ILD subjects and hence early encroachment into Range 2 during the more demanding p o s i t i v e work when compared to the healthy subjects. In contrast, the VE during negative work was only s l i g h t l y greater than the healthy subjects. The absolute VT was s i m i l a r or s l i g h t l y higher than the healthy subjects implying a higher but below c r i t i c a l VT/VC r a t i o , for the Range 2 v e n t i l a t o r y response. Hence the fb was only s l i g h t l y higher due to the greater v e n t i l a t o r y demand on the two ILD subjects. In summary for the two ILD subjects during p o s i t i v e work, t h e i r physiological responses during exercise were elevated compared to healthy middle-aged subjects. Even at the 1 3 8 low work rate of 60 Watts, one ILD subject had d i f f i c u l t y completing the p o s i t i v e work protocol. In contrast, during negative work at the same work rate, both subjects were able t cycle longer and with lower physical exertion. V Limitations The number of ILD subjects was small i n t h i s preliminary report on exercise responses during p o s i t i v e and negative work. The BMI of the two ILD subjects were also higher than the mean value f o r the healthy subjects. Further, one subject was male and the other female, both of whom were older than the mean age f o r the healthy male subjects. Thus, we could only glean general trends between the two ILD subject and the 12 healthy men. This preliminary work v e r i f i e d the s u i t a b i l t y of our research design f o r the i n c l u s i o n of subjects with ILD, and that steady-rate work may be maintained by i n d i v i d u a l s with s i g n i f i c a n t disease. Future t r i a l s are planned to extend t h i s work. VI C l i n i c a l Implications Since negative work e l i c i t e d lower physiological responses and ILD subjects may be able to exercise longer performing t h i s type of work, the ro l e of negative work i n 139 exercise t e s t i n g and t r a i n i n g of ILD subjects warrants more d e t a i l study. 140 

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