Open Collections

UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

The effects of prolonged strenuous exercise on beta-receptor responsiveness in male and female triathletes Scott, Jessica 2005

You don't seem to have a PDF reader installed, try download the pdf

Item Metadata


ubc_2005-0629.pdf [ 1.52MB ]
JSON: 1.0077033.json
JSON-LD: 1.0077033+ld.json
RDF/XML (Pretty): 1.0077033.xml
RDF/JSON: 1.0077033+rdf.json
Turtle: 1.0077033+rdf-turtle.txt
N-Triples: 1.0077033+rdf-ntriples.txt
Original Record: 1.0077033 +original-record.json
Full Text

Full Text

THE EFFECTS OF PROLONGED STRENUOUS EXERCISE ON BETARECEPTOR RESPONSIVENESS IN MALE AND FEMALE TRIATHLETES by JESSICA SCOTT B.Sc, The University of Alberta, 2003  A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE D E G R E E OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES HUMAN KINETICS  THE UNIVERSITY OF BRITISH COLUMBIA September 2005 © Jessica Scott, 2005  ABSTRACT The purpose of this investigation was to determine whether alterations in p-receptor responsiveness occur as a result of a single bout of prolonged strenuous exercise (PSE), and whether the myocardium of males and females responds differently to PSE. We examined nine male and eight female triathletes during three separate sessions: before, immediately after, and 24h following a half-ironman triathlon. Athletes were assessed during each session using dobutamine stress echocardiography. Steady-state graded infusions of dobutamine were used to assess p-adrenoreceptor responsiveness. Slopes calculated from linear regressions between dobutamine doses and changes in heart rate and contractility for each subject were used as an index of (3-adrenoreceptor responsiveness. Fractional shortening decreased from baseline after the race in both males and females, with the decrease greater in males (males: 54.1 ±2.1 to 50.7 ± 3.4% vs. females: 55.4 ± 2.7 to 53.3 ± 2.5 %). Despite no change in preload, systolic function (stress-shortening relationship) was significantly decreased in males and females following PSE. The amount of dobutamine necessary to increase HR 25 beats min- (males: 29.6 ± 6.6 to 42.7 ± 1  12.9 ugkg- min- vs. females: 23.5 ± 4.0 to 30.0 ± 7.8 ugkg- min- ) and contractility 10 mmHg-cm1  2  1  1  1  (males: 20.9 ± 5.1 to 37.0 ±11.5 ug kg- min- vs. females: 22.6 ± 6.4 to 30.7 ± 7.2 ug kg- min- ) 1  1  1  1  was significantly greater in both males and females post-race, with the amount of drug necessary to induce this change significantly greater in males. These results provide evidence that an acute bout of PSE results in reduced LV systolic function and dobutamine responsiveness in both males and females and that these alterations occur to a greater extent in males.  ii  Table of Contents ABSTRACT List of Tables List of Figures Acknowledgments SCIENTIFIC SUMMARY Cardiac Fatigue Underlying Mechanisms of Cardiac Fatigue Gender Differences STATEMENT OF THE PROBLEM HYPOTHESES RESEARCH METHODS Participants Genera/ Protocol Maximal Exercise Non- Exercise Conditions Prolonged Exercise Measurement offi-receptor Responsiveness Echocardiography Statistical Analysis RESULTS Prolonged Strenuous Exercise Echocardiography at Baseline Cardiovascular Responses to Dobutamine Chronotropic Responses to ^-Adrenergic Stimulation DISCUSSION PRACTICAL IMPLICATIONS REFERENCES  iii  ii iv v vi 1 1 3 6 7 7 8 8 8 8 8 8 9 9 10 10 10 10 11 11 12 15 26  List of Tables Table 1. Table 2. Table 3.  Selected physiological variables in male and female triathletes Cardiovascular responses to dobutamine infusion PRE, POST, and REC Dose response relationships between heart rate, contractility and dobutamine  iv  16 17 23  List of Figures  Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7.  Male stress-shortening relationship PRE, POST and REC Female stress-shortening relationship PRE, POST, and REC Myocardial mechanoenergetics PRE, POST, and REC Dobutamine induced cardiovascular changes PRE and POST Percent dobutamine induced cardiovascular changes PRE, POST, and REC Dobutamine dose necessary to increase HR 25 beatsmin- PRE, POST, and REC Dobutamine dose necessary to increase contractility 10 mmHgcm- PRE, POST, and REC  18 19 20 21 22  1  24  2  v  25  Acknowledgments  I want to extend a very special thank you to my supervisor, Dr. Darren Warburton, who has given me guidance beyond that which I ever could have imagined. Dr. Warburton's research expertise, genuine interest, thoroughness, and the many hours spent providing much valued support will always be appreciated. I wish to thank my committee members, Mark Haykowsky and Don McKenzie, for their instruction and guidance throughout the completion of my degree. Without the encouraging and upbeat help of Dr. Saul Isserow and the staff at the Cardiovascular Unit at the UBC hospital this project would not have been successful. I was introduced to the remarkable world of cardiovascular research by Mike Stickland, and the "jamin' with Sticky sessions' were an integral part of my decision to continue along the research path. I am very appreciative of the help from Dr. Shannon Bredin, Dr. Mike Koehle, Dr. Bevan Hughes, Lan Hu, Domink Zbogar, Arlana Taylor and Megan McNutt on the day of the triathlon. And finally, I couldn't have accomplished this without the undeviating encouragement and support of Ben Esch. I would like to dedicate this thesis to my mom, Joan Scott, who instilled in me the desire and motivation to achieve any goal I set in life. With her encouragement, guidance, and daily display of hard work and perseverance, I am inspired to attain more.  vi  SCIENTIFIC SUMMARY  The performance of the human body during endurance activities has been a focus of interest for many years. Recent investigations in the area of sport cardiology examining the effects of prolonged exercise on cardiovascular function have reported surprising findings. Two areas of particular interest in sport cardiology include cardiovascular drift and cardiac fatigue. After approximately ten minutes of moderate intensity exercise, cardiovascular drift occurs. This phenomenon is characterized by a progressive decline in stroke volume (SV) and pulmonary and systemic mean arterial pressures. These reductions are accompanied by a parallel increase in heart rate (HR), which enables cardiac output (Q) to be maintained (9). While it has been well documented and generally accepted that cardiovascular drift occurs during prolonged strenuous exercise (PSE), the reasons underlying this occurrence remain highly disputed (22, 23, 37). Similarly, much debate is centred around the possible mechanisms which are responsible for creating impaired systolic function (cardiac fatigue). Systolic function is both load and contractile dependent, and a change in any one or a combination of factors including preload, afterload or contractility could negatively affect left ventricular (LV) systolic function. While results from several studies suggest that changes in contractility occur during prolonged exercise (14,15,17, 29, 34,39,40, 52), others have found no such evidence (24,46,53, 56). Most investigations conclude that the underlying mechanisms responsible for alterations in LV systolic function need further examination. Cardiac Fatigue  The occurrence of cardiovascular drift during prolonged exercise may result not only in altered haemodynamic loading of the heart, but also, by decreasing cardiac efficiency, it may contribute to another phenomenon - cardiac fatigue. While it is well known that individuals with underlying cardiac anomalies have an increased risk of sudden death while exercising (59), recent studies have reported  1  that even healthy individuals with no evidence of underlying cardiovascular pathologies may have impairments in LV performance after prolonged exercise (14, 34, 52,65). A reduction in intrinsic pump function with prolonged exercise independent of haemodynamic loading was first suggested by Saltin and Stenberg (50) who observed a decrease in stroke volume (SV) after three hours of exercise, despite a maintenance of blood volume. More recent investigations of prolonged exercise include activities such as running (40,47,52), long distance triathlon races (14,15,17, 27,45, 48,65), and prolonged cycling (19, 24, 30). Cardiac function in these investigations was measured via echocardiography before the exercise period, immediately after the exercise period, and anywhere from 60 minutes to two days post-exercise. Results from each of these studies demonstrated that immediately post-exercise LV contractility was impaired. While many authors use ejection fraction (EF) and fractional shortening (FS) as indices of contractility, because EF and FS are preload and afterload dependent, interpretation of significantly reduced ejection phase indices does not simply imply that a decrease in contractility occurred. Most investigations rely on the interpretation of end-diastolic volume/diameter (EDV/D) as an indicator of preload, and a decrease in preload has been reported by several authors following PSE (14,29,39,40, 50, 57,65). While a decrease in preload may negate any changes in contractility, a lack of significant correlation between the change in EDV and the change in FS implies that some factor other than preload may affect contractile performance. Shortening is also afterload dependent, and the majority of the aforementioned studies found either no change (14,52) or a decrease in wall stress or systolic blood pressure - measures of afterload (30,65). Several authors have concluded that a decreased or unaltered ventricular shortening in the presence of a decreased systolic blood pressure or wall stress suggest a depressed inotropic state (14, 52, 57, 65). While many investigations have demonstrated that there is an impairment in contractility following PSE, others involving marathon running (31,47), and cycling (24, 53) have found no evidence to suggest  2  that depressed systolic function occurs as a result of PSE. In an attempt to explain the divergent findings between investigations, Perrault et al. (47) suggested that the observed decrease in systolic blood pressure associated with no change in LV EDD may be indicative of impaired LV function. The duration of exercise and/or the extreme environmental conditions associated with these activities, such as Ironman Hawaii, may be factors which compromise LV function more than would normally occur in less severe environments (31). The modality of exercise may also explain these discrepancies (14,27,65). For instance, the triathlon may allow athletes to reduce local muscle fatigue by changing muscle groups, while maintaining stress of the myocardium (53). It is plausible that researchers conducting studies involving repetitive motions such as cycling or running may have observed an alteration in contractility, had local muscular fatigue been prevented. Underlying Mechanisms of Cardiac Fatigue  Several theories attempt to explain the mechanisms causing impaired LV function following PSE. The first mechanism that has been postulated to contribute to cardiac fatigue involves energy metabolism in the heart. Both McKechnie (35) and Seals et al. (52) suggested that LV function impairment could be the result of elevated free fatty acid (FFA) concentrations, leading to depressed myocardial contractility. High levels of FFA are known to suppress glycogen oxidation and may reduce the efficiency of mitochondrial respiration through uncoupling of electron transport (35). Conversely, Goodwin & Taegtmeyer (25) suggested that the glycolytic block imposed by FFA could be bypassed by the substrate lactate, thus improving cardiac energy homeostasis during exercise. This implies that energy metabolism does not contribute to LV dysfunction. Nozawa et al. (41,42) suggested that a decrease in stroke work (as a result of a decrease in SV and end-systolic pressure) may cause a decrease in myocardial efficiency during prolonged exercise. An alternative hypothesis put forward by several authors (49,65) postulates that the increase in catecholamine levels that occurs during exercise may lead to an increased vascular tone and decreased  3  myocardial blood supply, ultimately resulting in myocardial ischemia. On this note, it is possible that a small compromise in blood flow could induce metabolic acidosis in the myocardium (55). An increase in hydrogen ion concentration has been shown to substantially increase the calcium requirement for myofilament activation and to impair sarcoplasmic reticulum (SR) calcium uptake as well as calcium induced calcium release from the SR (55). O'Brien et al. (43) tested the hypothesis that SR failure is a consistent feature of cardiac and skeletal muscle fatigue, and concluded that failure of calcium sequestration by the SR plays a major role in the pathogenesis of cardiac and muscle fatigue and failure. Another mechanism proposed to result in a decreased inotropic state is a desensitization of cardiac preceptors. Investigators have long observed that, in clinical populations (such as those individuals with chronic heart failure) exposure of p-receptors to increased concentrations of catecholamines results in desensitization of these receptors (1, 20, 58). Vanoverschelde et al. (57) proposed that the increased exposure to catecholamines during prolonged exercise may cause a downregulation of p-adrenoreceptor responsiveness, prompting the decline in LV contractility in healthy athletes. Following an endurance run, Maron et al. (32) reported a 5-fold increase in catecholamines from resting levels, an increase which has also been observed following a marathon (12), a 100 km ultra-marathon (44), and a prolonged run to exhaustion (52). Given that prolonged exercise provides a lengthy exposure to these elevated catecholamines, it is possible that there is a down-regulation of p-receptors to below pre-exercising levels (12). This appears to be true in dogs, where prolonged dynamic exercise produced a significant decrease in sensitivity to the effects of p-adrenergic receptor stimulation (21). Recent investigations in humans have also revealed that prolonged exercise alters p-receptor responsiveness (16,19). Eysmann et al. (19) and Welsh et al. (62) examined p-receptor desensitization following a single bout of PSE, and demonstrated that not only EF was reduced following PSE, but also that this reduction was closely related to a decreased sensitivity to exogenous p-receptor stimulation.  4  A shift of sarcolemmal p-receptors to an intracellular location following exercise has been demonstrated in rats, suggesting that prolonged exercise may result in p-receptor downregulation, in addition to p-receptor desensitization. Werle et al. (63) investigated the cardiac p-receptor adaptation to physical activity in four groups of rats: 1) control group (remained sedentary), 2) acute endurance exercise group (remained untrained and swam once for two hours), 3) endurance training group (swam continuously for two hours per day for six weeks), and 4) maximal training group (swam three times per day for 2-3 minutes within 3 hours, with 10% of body weight attached to tails for six weeks). They reported a decrease in the number of cardiac p-receptors by 25.5% in the maximal training group, 13.0% in the endurance-training group, and 16.6% in the acute endurance group (63). An early investigation by Butler et al. (5) into p-receptor function in human athletes reported that there were decreases in sympathetic nervous system responsiveness following physical training, and that these results were related to decreases in lymphocyte p-receptor density. They hypothesized that the reductions in receptor density at higher levels of physical fitness were a protective mechanism against the chronic exposure to high concentrations of catecholamines. Human lymphocytes contain p-receptors that are regulated by changes in circulating catecholamines, and many investigations have utilized this non-invasive approach for studying cardiac p-receptor regulation (2,13,38). Eysmann et al. (19) also examined lymphocyte preceptor density following prolonged exercise, but reported no differences between pre- and postexercising levels. These contradictory results may be due to the accuracy of using lymphocytes preceptors as a surrogate to cardiac p-receptors, as several investigations have demonstrated that total preceptor density in the heart is significantly lower than that measured in peripheral lymphocytes (2, 3, 36, 64).  5  Gender Differences  Several studies have shown that significant sexual dimorphisms exist in neuroendocrine and metabolic responses to physiological stresses (10). In response to exercise, men may have increased catecholamine and norepinephrine responses, as well as enhanced cardiovascular parameters such as systolic and mean arterial pressure (10). Non-invasive measurements of autonomic neural control of heart rate using heart rate variability (HRV) have also indicated that females have greater parasympathetic and less sympathetic control of heart rate than do males at rest and during exercise (18). Several other investigations examining ventricular function have also demonstrated gender differences in cardiovascular regulation, although with conflicting results. Vizgerda et al. (60) established that cardiac myocytes from male rats have an enhanced response to p-adrenergic stimulation. They hypothesized that this could be attributed to augmented p-adrenergic signalling resulting in a greater transsarcolemmal calcium influx (60). This group also reported a twofold greater density of p-receptors in male myocytes compared to female myocytes (60). Similarly, Schaible et al. (51) demonstrated that cardiac function was greater in male rats as opposed to female rats. This finding was not supported by Capasso et al. (6) who reported that isolated papillary muscles from female rats had greater contractile performance than those from male rats. Investigations on humans by Convertino (8) supported the findings of Capasso et al. (6), and suggested that a greater tachycardic response in females during isoproterenol infusion was primarily due to higher p-receptor responsiveness. Ejection fraction (4) and fractional shortening (11) have also been shown to be higher in women compared to men. Interestingly, a recent study examining cardiac performance during PSE in female triathletes did not find a decline in LV systolic function following a 40 km cycle and 10 km run (33). Given that the majority of investigations reporting declines in cardiac performance following PSE include male participants only, as well as the  6  significant sexual dimorphisms in cardiac function reported in the literature, it is important to examine the gender differences in cardiac performance that may occur following PSE. STATEMENT OF THE PROBLEM Although numerous investigations have examined the occurrence of cardiac fatigue during PSE, very few have studied this phenomenon in females. Several studies have shown that significant sexual dimorphisms exist in neuroendocrine and metabolic responses. In response to exercise, men may have increased catecholamine and norepinephrine responses, as well as enhanced cardiovascular parameters such as systolic and mean arterial pressure. Non-invasive measurements of autonomic neural control of heart rate using heart rate variability (HRV) have also indicated that females have greater parasympathetic and less sympathetic control of heart rate than males. Therefore, women may not experience or have as great of a catecholamine-mediated p-receptor desensitization. The purpose of the proposed study was to examine whether alterations in p-adrenergic responsiveness occur in healthy humans in response to a single bout of PSE, and whether the myocardium of males and females responds differently to prolonged physical exertion. HYPOTHESES 1.  As a result of PSE of greater than five hours, both males and females will have decreased myocardial contractility.  2. As a result of PSE, males will have larger alterations in cardiac p-receptor responsiveness relative to females. 3.  As a result of greater heart p-receptor alterations, males will exhibit greater evidence of cardiac fatigue relative to females.  7  RESEARCH METHODS Participants  Nine male and eight female endurance-trained triathletes were recruited to complete a half-ironman triathlon. All athletes had been exercising regularly 5-7 days per week for a minimum of two years, and all were competing in athletic events on a regular basis. None had any known form of cardiovascular disease. Participant characteristics are shown in Table 1. The study protocol was approved by the Clinical Research Ethics Board of the University of British Columbia and all subjects gave their written consent to participate in this study. General Protocol  Participants underwent four separate testing days: 1) PRE (familiarization and V02max), 2) BASE (6 days prior to PSE), 3) POST (immediately following PSE), and 4) REC (24 h following PSE). Participants were instructed to refrain from exercise and abstain from caffeine and other autonomic stimulants such as prescription and non-prescription drugs for at least 48 h before each experimental protocol. Maximal Exercise  During the PRE session, V02max and maximum heart rate were determined with a graded maximal cycle ergometer test consisting of 2-minute workload increments. After a standardized 5 minute warm-up period, workload increased by 30 W every minute, during which expired and ventilatory parameters were acquired using a metabolic cart (PhysioDyne, Max-1; USA). Non- Exercise Conditions  During BASE and REC sessions, two-dimensional and Doppler echocardiography were performed while participants rested supine for 10 min. Continuous incremental infusions of dobutamine were then administered intravenously (see measurement of ^-receptor responsiveness below). Prolonged Strenuous Exercise  All athletes completed a half-lronman triathlon race involving a continuous 1.5 km swim, 90 km cycle, and 21.1 km run. The racing event was conducted during a sunny day (temperature 13°C, precipitation 0  8  mm and wind speed 12 km-hour ). Athletes were encouraged to consume fluid ad libitum during the race, 1  and data was collected within 15 min of race completion in all participants. Measurement of 0-receptor Responsiveness  During the BASE, POST and REC sessions participants underwent a dobutamine stress test. After acquisition of baseline resting images infusion of the p-receptor agonist dobutamine was commenced where incremental doses of the drug (0, 5,10, 20, 30, and 40 ug kg- min- ) were administered every 1  1  three minutes. Continuous HR was measured from an electrocardiogram, and beat-by-beat changes (corrected each minute) in SBP, DBP and MAP were measured non-invasively (Finapres, Ohmeda). Linear regression relationships were constructed relating the increase in HR and contractility to the dose of dobutamine. As previously described (7,8,19, 28,54), the slopes describing the linear stimulusresponse relationship between the dose of dobutamine versus HR and contractility provided a measure of the responsiveness of cardiac p-receptors. Differences in slopes, y-intercepts and x-intercepts between BASE, POST and REC conditions were compared by analysing the least squares linear estimates generated by each participant. Echocardiography  Two-dimensional and Doppler echocardiography were performed during all p-receptor sensitivity assessments. Left ventricular two-dimensional images were obtained in the long axis, short axis (midpapillary muscles) and apical 2 and 4 chamber views according to the American Society of Echocardiography guidelines. A minimum of three cardiac cycles were averaged for analysis. Left ventricular systolic function was evaluated using ejection fraction, fractional shortening, end-systolic meridional wall stress, and myocardial contractility (SBP/end-systolic cavity area). Pulsed Doppler recordings were employed to assess diastolic filling; in particular, early (E) and atrial (A) peak velocities were measured and the ratio of early to late diastolic filling (E:A) was calculated. Myocardial efficiency was calculated as ((0.38 x stroke work)/pressure volume area) and myocardial oxygen consumption was  9  calculated as ((1.75x10 x pressure volume area + .03) x HR) during each dobutamine dose in each 5  condition PRE, POST, and REC). Statistical Analysis Differences between echo-Doppler measures of cardiac function, between dobutamine responses at rest and after prolonged exercise were examined using repeated-measures analysis of variance with Tukey post hoc comparisons. The level of significance was set a priori at p < 0.05. Data are presented as means + SE at BASE, POST and REC respectively.  RESULTS Prolonged Strenuous Exercise All athletes successfully completed the half ironman triathlon with average finishing times of 4h 45min + 15min for males and 5h 16min + 21 min for females. Echocardiography at Baseline At resting baseline (i.e. dobutamine dosage 0 ugkg- min- ) PRE, males and females had normal values 1  1  for LV cavity dimensions, wall thickness, fractional shortening and wall stress (Table 2). There were no differences between males and females for measures of end-systolic dimension, contractility, fractional shortening, and wall stress at resting baseline (p<0.05). However, males had significantly greater enddiastolic dimension (5.4 ± 0.2 vs. 5.0 ± 0.1 cm) and E:A (2.10 ± 0.5 vs. 1.83 ± 0.3) relative to females. At race finish (POST), diastolic dimension (preload) was not changed from baseline measures in either group (p<0.05). Systolic dimension and HR were significantly increased in males and females POST, while systolic blood pressure was significantly decreased in both groups. Fractional shortening, myocardial contractility, and wall stress were significantly decreased, while end-systolic dimension was significantly increased POST in males and females (Table 2; dobutamine dosage 0 ug kg- min- ). 1  1  However, the decrease in fractional shortening and wall stress were significantly greater in males relative to females. The linear, inverse correlation between stress and shortening was displaced downward POST, as measured by a comparison of the y-intercepts, indicating less shortening for a given afterload 10  in both males and females (Figures 1 and 2). Myocardial VO2 was significantly higher in males relative to females across all conditions. Myocardial VC^was increased POST in both groups. While myocardial efficiency was significantly reduced POST in both males and females, females maintained their efficiency to a greater extent when compared with PRE (p<.05; Figure 3). All measures returned to baseline values 24 h following PSE (i.e. during REC). Cardiovascular Responses to Dobutamine  Contractility increased significantly in response to dobutamine in both groups PRE (Figure 4). However, the increase in contractility was significantly greater in males than in females at the higher doses. Systolic blood pressure increased significantly in response to dobutamine in both groups, but females demonstrated a smaller rise in SBP (p<0.05) than did males PRE (Figure 4). Dobutamine induced increases in heart rate in both males and females (p<0.05). However, males exhibited a diminished chronotropic response to dobutamine compared with females PRE (p<0.05; Figure 4). At race finish (POST), contractility, heart rate, and systolic blood pressure increased in response to dobutamine in males and females (Figure 4). However, the dobutamine induced change in contractility, heart rate and systolic blood pressure (expressed as % change from control to maximum dosage -- i.e. % change from 0 to 40 pgkg- min- ) was significantly less POST in males and females when compared to PRE (Figure 1  1  5). Additionally, the percent change from PRE to POST was significantly greater in males relative to females (Figure 5). All measures returned to baseline values 24 h following PSE (i.e. during REC). This indicates a gender difference in B-adrenergic mediated cardiovascular changes, both at rest and following PSE, in response to dobutamine. Chronotropic Responses to ^-Adrenergic  Stimulation  The chronotropic sensitivity to dobutamine, determined by the slope of the linear portion of the heart rate dobutamine and contractility dobutamine dose-response curve, was significantly greater with a steeper slope in females than in males PRE (Table 3). Dobutamine doses necessary to increase HR were significantly increased following PSE in both males and females; however, the differences were 11  significantly greater in males (Figure 6). Dobutamine doses necessary to increase contractility were also significantly increased in males and females post race (Figure 7). Males required significantly more dobutamine than females to induce these changes following PSE, as evidenced by increases in slopes and x-intercepts of the dose response relationships between HR, contractility and dobutamine (Table 3). DISCUSSION The present study demonstrated that, as has been previously shown LV fractional shortening and contractility are reduced following PSE. This investigation is the first to demonstrate that, although LV systolic function is reduced after PSE in both male and female triathletes, the reduction in cardiac performance occurs to a greater extent in male athletes. Our results also suggest that the decreased inotropic state produced by PSE may, in part, be due to alterations in cardiac p-receptor responsiveness. Investigators have previously observed that long-term exposure of adrenergic receptors to increased concentrations of catecholamines results in desensitization of these receptors. This phenomenon has clinical relevance for individuals with congestive heart failure, where elevated catecholamines and altered adrenergic responsiveness have been implicated in the pathogenesis of heart failure. Our finding of a decrease in response to dobutamine suggests that a similar mechanism may be functioning in response to physiological stimuli in healthy males and females. While the detrimental effects of chronically elevated catecholamines on cardiac function have been demonstrated in cardiac patients, few studies have closely examined agonist-induced desensitization with PSE. Friedman et al. (21) demonstrated a decreased cardiac chronotropic responsiveness to isoproterenol after 60 min of exercise in the dog; however, did not assess LV function. In endurancetrained pigs, the diminished chronotropic response was associated with selective downregulation of the P-receptors in the right atrium (26). Recent investigations in humans have also revealed that prolonged exercise may alter p-receptor responsiveness (16,19). Eysmann et al. (19) examined p-receptor  12  desensitization using isoproterenol following a single bout of PSE, and demonstrated not only that EF was reduced following prolonged exercise, but also that this reduction was closely related to a decreased sensitivity to exogenous p-receptor stimulation. Welsh et al. (62) recently investigated adrenoreceptor responsiveness following PSE using the B-receptor agonist dobutamine, and reported blunted chronotropic and inotropic responses. Due to its predominantly inotropic stimulation and the ability to be administered as a continuous infusion, the present investigation used dobutamine as a B-agonist. This is the first investigation to assess gender differences in the heart rate, blood pressure and myocardial contractility responses during a continuous inotropic infusion following PSE. The present investigation also demonstrates a close relationship between the inotropic response to dobutamine and changes in LV EF with prolonged exercise. Several studies have demonstrated that PSE produces transient alterations in LV systolic function and diastolic filling parameters (E:A) that are independent of changing preload and afterload. Our findings are concordant with these reports, and furthermore suggest that reduced systolic function with PSE may, in part, be mediated by impaired adrenergic responsiveness. While Eysmann et al. (19) and Welsh and coworkers (62) demonstrated that alterations in P-receptor responsiveness occur following PSE, no investigation to our knowledge has examined the potential gender differences in B-receptor responsiveness following a half-ironman triathlon. Several studies have shown that significant sexual dimorphisms exist in neuroendocrine and metabolic responses to physiological stresses (10). In response to exercise, men may have increased catecholamine and norepinephrine responses, as well as enhanced cardiovascular parameters such as systolic and mean arterial pressure (10). These increased sympathetic responses could then result in greater P-receptor desensitization. The present investigation supported these suggestions by demonstrating that men exhibit significantly greater alterations in P-receptor sensitivity relative to females following PSE.  13  Several limitations need to be considered for this investigation. First, it is possible that baroreflex changes and vagal responses to dobutamine may have affected the observed differences in contractility response. However, Friedman et al. (21) found that the functional desensitization following exercise was evident with and without pretreatment with atropine, suggesting that the phenomenon was unrelated to changes in vagal tone. Furthermore, the functional expression of desensitization to another B-agonist, isoproterenol, during exogenous catecholamine administration has been shown to be independent of baroreceptor reflexes and ganglionic activity (19). This suggests that our findings reflect true impairment of the intrinsic sinus node response to B-adrenergic stimulation. Second, differences in heart rate between rest and prolonged exercise may have influenced results. Increasing heart rate is known to improve LV performance (52), potentially through a rate-dependent increase in calcium availability. However, because an increase in heart rate is thought to enhance LV performance, our findings of decreased performance may be even more significant. Finally, the use of human volunteers to assess cardiovascular function is limited, as it is difficult, if not impossible, to assess ventricular inotropic state in humans without removing the heart following intervention. As a result of this limitation, the surrogate measures of ejection fraction, fractional shortening and wall stress were used as indices of contractility. In conclusion, the present investigation demonstrates that PSE in healthy male and female triathletes is associated with impaired cardiac inotropic responsiveness to dobutamine. This likely represents impairment of the sinus node or right atrial response to B-receptor stimulation, although neither vagal nor baroreceptor influences can be excluded. The inotropic changes are closely related to the decrement in LV EF. These data suggest that the altered cardiac performance which occurs following PSE may be mediated, in part, by impaired cardiac adrenergic responsiveness. Delineation of the mechanisms of such altered responsiveness and its physiological relevance for cardiovascular performance during exercise in healthy adults or in those with diseased hearts requires further investigation.  14  PRACTICAL IMPLICATIONS  Results from this investigation demonstrate that following prolonged exercise there is a reduction in systolic function, which is mediated by impaired adrenergic responsiveness. Since exercise is so widely prescribed for health promotion, the possibility of transient reductions in heart function occurring as a result of too much exercise has significant implications for both athletic and non-athletic populations. Prolonged exercise may result in myocardial inefficiency and increased myocardial oxygen demands. This may ultimately impact oxygen delivery and endurance performance. In addition to demonstrating a reduction in cardiac function following prolonged exercise, this investigation also established that the myocardium of males responds differently than that of females. This finding may have significant implications not only for individualized training purposes, but also for prescription of exercise for clinical populations. For example, since we have demonstrated that males have greater p-receptor desensitization relative to females following prolonged exercise, it may be beneficial for males to exercise with interval sessions rather than prolonged sessions. Warburton et al. (61) have demonstrated that the same cardiovascular benefit of prolonged sessions can be obtained during a much shorter time period with interval sessions, thus reducing the time the cardiac tissue is exposed to catecholamines, and potentially reducing the occurrence of cardiac fatigue.  15  Table 1. Selected physiological variables in male and female triathletes  Variable  Males (n= 9)  Females (n= 8)  Age, yr Height, cm  30 + 2.6 178 + 2.6x 77.8 + 3.4x 13.3±2.3x 57.5 + 2.3x  34 + 2.6 165 + 2.2 63.2 + 3.3 22.4 ±4.1 46.8 + 2.5  Weight, kg Body fat, % VC^max, mL-kg min 1  1  x p<0.05 vs. females. Values are means ± SE.  16  Table 2. Cardiovascular responses to dobutamine infusion PRE, POST, and REC  Dobutamine Dosage (ug kg- min- ) 1  0 Variable  M  EDD, cm PRE POST REC ESD, cm PRE POST REC FS, % PRE POST REC Cont, mmHgcnv PRE POST REC  5 F  M  1  10 F  M  20 F  M  30 F  M  40 F  M  F  5.4±0.2T 5.4I0.2T 5.4±0.2T  5.010.1 4.9+0.1 4.9+0.1  5.410.2T 5.410.2T 5.410.2T  5.0+0.1 4.910.1 4.910.1  5.4!0.2T 5.4l0.2x 5.4i0.2x  5.010.1 4.910.1 4.910.1  5.4I0.2T 5.410.2T 5.4I0.2T  5.010.1 4.910.1 4.9+0.1  5.4+0.2T 5.4i0.2x 5.4l0.2x  5.010.1 4.910.1 4.910.1  5.410.2T 5.4i0.2x 5.410.2T  5.010.1 4.910.1 4.910.1  3.0±0.2 3.7±0.2*T 3.110.1  3.0+0.2 3.310.1* 2.910.2  3.0+0.1 3.5l0.2*T 2.910.1  2.910.2 3.1+0.1* 2.810.2  2.9+0.1 3.3I0.2*T 2.810.1  2.710.2  2.510.2 3.1i0.2*T 2.510.1  2.310.2 2.510.1* 2.410.2  2.310.2 2.8i0.2*x 2.310.1  2.1+0.2 2.310.1* 2.210.2  2.010.1 2.610. 1*T 2.010.2  1.910.2 2.110.1* 2.010.2  54.1±0.8 50.7+1.1*T 52.6±1.3  55.410.9 53.311.6* 56.710.9  59.211.5 54.0i2.0*T 59.610.7  59.411.3 67.811.9 57.712.0* 59.1i2.0*T 59.311.0 65.7+0.7  64.1+1.4 63.211.5 63.7+1.3  71.412.3 63.6l2.3*T  73.811.5  72.111.5 75.910.9 68.311.7* 71.111.2* 71.811.1 77.211.5  74.611.2 79.610.8 76.4+1.2 72.611.2* 73.411.3*T 75.110.9*  11.510.6 10.310.6* 11.5+0.3  12.510.5 11.8+0.5* 12.3+0.4  12.711.0 11.7+0.7* 12.210.3  13.710.5 13.9+0.5 13.5+0.4  17.210.6 21.010.7 15.510.7* 15.211.7* 18.010.7 21.711.3  19.510.3 25.9I0.6T 18.010.9* 19.511.8* 22.7+1.5 26.511.3  25.210.8 32.6I0.6T 30.2+0.7 23.011.6* 22.611. 8*T 25.711.2* 26.512.0 30.111.1 30.1+1.8  74.3+1.6 67.8i4.4*T 75.911.0  72.513.5  67.412.5 64.0i4.7*T 61.912.5  68.815.1  2.810.1*  2.710.2  75.711.5  79.2+0.9  77.411.3  2  17.110.7 12.4+1.1* 15.010.6  CTES,  dynescrrv PRE POST REC  2  69.815.6*  72.414.5  53.813.3 62.715.1 52.514.1 48.815.0 49.812.3 45.713.8 42.4+1.6 40.413.0 61.716.8* 57.3i3.9Y 53.6+5.2* 56.5i6.9*T 46.314.2* 44.5+3.7*T 41.013.8* 39.614.2* 38.612.8* 61.614.3 53.511.9 57.213.5 44.014.1 49.414.0 41.714.4 44.013.7 39.513.5 39.712.9  EDD, end-diastolic diameter; ESD, end-systolic diameter; FS, fractional shortening; Cont, contractility; QES, end-systolic wall stress. * p<0.05 vs. baseline, T p<0.05 vs. females.Values are means ± SE.  Figure 1. Male stress-shortening relationship PRE, POST and REC  •  —i 40  —  PRE P R E Line of Identity  1  1  60  80  —  100  Wall Stress (dynes cm" ) 2  Calculated regression in males for end-systolic wall stress plotted against fractional shortening on pre race, post race and recovery recordings (prior to dobutamine administration). The regression line characterizing the stress-shortening relationship post race is displaced downward (y axis intercepts are lower). * p<0.05 vs. baseline.  18  Figure 2. Female stress-shortening relationship PRE, POST, and REC  •  PRE P R E Line of Identity POST P O S T Line of Identity REC R E C Line of Identity  • A  60 H  co  'E  a  o W  50  7c5 o u (0  40 /  40  60  80  100  Wall Stress (dynes cm" ) 2  Calculated regression in females for end-systolic wall stress plotted against fractional shortening on pre race, post race and recovery recordings (prior to dobutamine administration). The regression line characterizing the stress shortening relationship post race is displaced downward (y axis intercepts are lower). * p<0.05 vs. baseline.  19  Figure 3. Myocardial mechanoenergetics PRE, POST, and REC  -  16-,  'c  "I  14  c  12 -\  o a. E  10  3 W  o o  8H  a>  6 H  =  I Males D Females  c  O) X  O T3  4  T: L_  O  O  2  >. PRE  POST  REC  PRE  POST  REC  30  25 o c  .2  20  "o £  15  re  10  u o >»  Experimental Condition  Alterations in myocardial mechanoenergetics characterized by increases in myocardial oxygen consumption in males and females; and decreases in myocardial efficiency in males POST. * p<0.05 vs. baseline, T p<0.05 vs. females.Values are means ± SE.  20  Figure 4. Dobutamine induced cardiovascular changes PRE and POST  Dobutamine increased all variables in both groups however, females showed a greater HR response, while males demonstrated a greater contractility and SBP response PRE and POST. Males also had greater decreases in all variables POST. * p<0.05 vs. baseline, x p<0.05 vs. females.Values are means ±SE.  21  Figure 5. Percent dobutamine induced cardiovascular changes PRE, POST, and REC  PRE  30  POST  REC  PRE  POST  REC  PRE  POST  REC  -i  Experimental Condition  Percent change from 0 to 40 ugkg- min- in contractility, HR, and SBP was significantly different between males and females PRE and POST. The drop PRE to POST in percent change was significantly greater in males relative to females. * p<0.05 vs. baseline, T p<0.05 vs. females. Values are means ± SE. 1  1  22  Table 3. Dose response relationships between HR, contractility and dobutamine  BASE  POST  REC  X-INTERCEPTS: DOBUTAMINE DOSES (ug kg- min- ) HR, beats/min 1  Males Females Contractility, mmHg c m  1  29.6 ±6.6 23.5 ± 4  42.7±12.9*x 30.0 ±7.8*  29.3 ±5.9 23.4 ±10.0  20.9 ±5.1 22.6 ±6.4  37.0 ± 11.5*T 20.4 ±4.5 30.7 ±7.2* 24.0 ±10.2  2  Males Females  SLOPES: p-RECEPTOR RESPONSIVENESS HR, beats/min Males Females Contractility, mmHg c m Males Females  0.93 ±0.33 1.30 ±0.48  0.68±0.19*x 1.02± 0.31*  0.96 ±0.19 1.34 ±0.46  0.52 ±0.11 0.46 ±0.10  0.31 ± 0.12*x 0.33 ±0.09*  0.52± 0.09 0.48 ±0.14  2  HR, heart rate. * p<0.05 vs. baseline, x p<0.05 vs. females. Values are means + SE.  23  Figure 6. Dobutamine dose necessary to increase HR 25 beats m i n PRE, POST, and REC 1  PRE  POST  REC  Experimental Condition  Differences in chronotropic sensitivity to dobutamine between males and females. * p<0.05 vs. baseline, x p<0.05 vs. females. Values are means + SE.  24  Figure 7. Dobutamine dose necessary to increase contractility 10 mmHg c m PRE, POST, and REC 2  50 l |  40  3 0) O) (0 W  30  Q 0)  20  Males l Females  X  I  o c  E 3  -Q 10 O Q  PRE  POST  REC  Experimental Condition  Differences in inotropic sensitivity to dobutamine between males and females. * p<0.05 vs. baseline, T p<0.05 vs. females. Values are means + SE.  25  REFERENCES 1.  Bristow MR, Ginsburg R, Umans V, Fowler M, Minobe W, Rasmussen R, Zera P, Menlove  R, Shah P, Jamieson S, and et al. Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. C/'rc Res 59: 297-309,1986. 2.  Brodde OE, Kretsch R, Ikezono K, Zerkowski HR, and Reidemeister JC. Human beta-  adrenoceptors: relation of myocardial and lymphocyte beta-adrenoceptor density. Science 231:15841585,1986. 3.  Brodde OE, Michel MC, Gordon EP, Sandoval A, Gilbert EM, and Bristow MR. Beta-  adrenoceptor regulation in the human heart: can it be monitored in circulating lymphocytes? Eur Heart J 10 Suppl B: 2-10,1989. 4.  Buonanno C, Arbustini E, Rossi L, Dander B, Vassanelli C, Paris B, and Poppi A. Left  ventricular function in men and women. Another difference between sexes. Eur Heart J 3:525-528,1982. 5.  Butler J, O'Brien M, O'Malley K, and Kelly JG. Relationship of beta-adrenoreceptor density to  fitness in athletes. Nature 298:60-62,1982. 6.  Capasso JM, Remily RM, Smith RH, and Sonnenblick EH. Sex differences in myocardial  contractility in the rat. Basic Res CardioUd: 156-171,1983. 7. Convertino VA. Evidence for altered alpha-adrenoreceptor responsiveness after a single bout of maximal exercise. J Appl Physiol %: 192-198,2003. 8. Convertino VA. Gender differences in autonomic functions associated with blood pressure regulation. Am J Physiol275: R1909-1920,1998. 9. Coyle EF. Cardiovascular drift during prolonged exercise and the effects of dehydration. Int J Sports Med 19 Suppl 2: S121-124,1998. 10.  Davis SN, Galassetti P, Wasserman DH, and Tate D. Effects of gender on neuroendocrine and  metabolic counterregulatory responses to exercise in normal man. J Clin Endocrinol Metab 85: 224-230, 2000. 11.  de Simone G, Devereux RB, Roman MJ, Ganau A, Chien S, Alderman MH, Atlas S, and  Laragh JH. Gender differences in left ventricular anatomy, blood viscosity and volume regulatory hormones in normal adults. Am J Cardiol 68:1704-1708,1991. 12. Dearman J and Francis KT. Plasma levels of catecholamines, Cortisol, and beta-endorphins in male athletes after running 26.2, 6, and 2 miles. J Sports Med Phys Fitness 23: 30-38,1983. 13.  DeBlasi A, Maisel AS, Feldman RD, Ziegler MG, Fratelli M, DiLallo M, Smith DA, Lai CY,  and Motulsky HJ. In vivo regulation of beta-adrenergic receptors on human mononuclear leukocytes: assessment of receptor number, location, and function after posture change, exercise, and isoproterenol infusion. J Clin Endocrinol Metab 63:847-853,1986. 14.  Douglas PS, O'Toole ML, Hiller WD, Hackney K, and Reichek N. Cardiac fatigue after  prolonged exercise. Circulation 76:1206-1213,1987. 15. Douglas PS, O'Toole ML, Hiller WD, and Reichek N. Different effects of prolonged exercise on the right and left ventricles. J Am Coll Cardiol 15:64-69,1990. 16. Douglas PS, O'Toole ML, and Katz SE. Prolonged exercise alters cardiac chronotropic responsiveness in endurance athletes. J Sports Med Phys Fitness 38:158-163,1998. 17. Douglas PS, O'Toole ML, and Woolard J. Regional wall motion abnormalities after prolonged exercise in the normal left ventricle. Circulation 82:2108-2114,1990. 18.  Evans JM, Ziegler MG, Patwardhan AR, Ott JB, Kim CS, Leonelli FM, and Knapp CF.  Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes. J Appl Physiol 91:2611-2618,2001.  26  19.  Eysmann SB, Gervino E, Vatner DE, Katz SE, Decker L, and Douglas PS. Prolonged  exercise alters beta-adrenergic responsiveness in healthy sedentary humans. J Appl Physiol 80:616622,1996. 20.  Fowler MB, Laser JA, Hopkins GL, Minobe W, and Bristow MR. Assessment of the beta-  adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response. Circulation 74:1290-1302,1986. 21. Friedman DB, Ordway GA, and Williams RS. Exercise-induced functional desensitization of canine cardiac beta-adrenergic receptors. J Appl Physiol 62:1721-1723,1987. 22. Fritzsche RG, Switzer TW, Hodgkinson BJ, and Coyle EF. Stroke volume decline during prolonged exercise is influenced by the increase in heart rate. J Appl Physiol 86:799-805,1999. 23. Gonzalez-Alonso J, Mora-Rodriguez R, and Coyle EF. Stroke volume during exercise: interaction of environment and hydration. Am J Physiol Heart Circ Physiol 278: H321-330, 2000. 24. Goodman JM, McLaughlin PR, and Liu PP. Left ventricular performance during prolonged exercise: absence of systolic dysfunction. Clin Sci (Lond) 100: 529-537,2001. 25. Goodwin GW and Taegtmeyer H. Improved energy homeostasis of the heart in the metabolic state of exercise. Am J Physiol Heart Circ Physiol 279: H1490-1501, 2000. 26.  Hammond HK, White FC, Brunton LL, and Longhurst JC. Association of decreased  myocardial beta-receptors and chronotropic response to isoproterenol and exercise in pigs following chronic dynamic exercise. Circ Res 60:720-726,1987. 27.  Haykowsky M, Welsh R, Humen D, Warburton D, and Taylor D. Impaired left ventricular  systolic function after a half-ironman race. Can J Cardiol 17:687-690,2001. 28. Hopkins MG, Spina RJ, and Ehsani AA. Enhanced beta-adrenergic-mediated cardiovascular responses in endurance athletes. J Appl Physiol B0: 516-521,1996. 29. Ketelhut R, Losem CJ, and Messerli FH. Depressed systolic and diastolic cardiac function after prolonged aerobic exercise in healthy subjects. Int J Sports Med 13: 293-297,1992. 30. Ketelhut R, Losem CJ, and Messerli FH. Is a decrease in arterial pressure during long-term aerobic exercise caused by a fall in cardiac pump function? Am Heart J127: 567-571,1994. 31.  Lucia A, Serratosa L, Saborido A, Pardo J, Boraita A, Moran M, Bandres F, Megias A, and  Chicharro JL. Short-term effects of marathon running: no evidence of cardiac dysfunction. Med Sci Sports Exert? 31:1414-1421,1999. 32. Maron MB, Horvath SM, and Wilkerson JE. Acute blood biochemical alterations in response to marathon running. Eur J Appl Physiol Occup Physiol 34:173-181,1975. 33. McGavock J, Haykowsky M, Warburton D, Taylor D, Quinney A, and Welsh R. Left  ventricular systolic performance during prolonged strenuous exercise in female triathletes. Dyn Med 2: 2, 2003. 34.  McGavock JM, Warburton DE, Taylor D, Welsh RC, Quinney HA, and Haykowsky MJ. The  effects of prolonged strenuous exercise on left ventricular function: a brief review. Heart Lung 31: 279292; quiz 293-274, 2002. 35.  McKechnie JK, Leary WP, Noakes TD, Kallmeyer JC, MacSearraigh ET, and Olivier LR.  Acute pulmonary oedema in two athletes during a 90-km running race. SAfrMedJ56: 36.  261-265,1979.  Michel MC, Beckeringh JJ, Ikezono K, Kretsch R, and Brodde OE. Lymphocyte beta 2-  adrenoceptors mirror precisely beta 2-adrenoceptor, but poorly beta 1-adrenoceptor changes in the human heart. J Hypertens SupplA: S215-218,1986. 37.  Mora-Rodriguez R, Hodgkinson BJ, Byerley LO, and Coyle EF. Effects of beta-adrenergic  receptor stimulation and blockade on substrate metabolism during submaximal exercise. Am J Physiol Endocrinol Metab 280: E752-760,2001. 38. Motulsky HJ, Cunningham EM, DeBlasi A, and Insel PA. Desensitization and redistribution of  beta-adrenergic receptors on human mononuclear leukocytes. Am J Physiol 250: E583-590,1986.  27  39.  Niemela K, Palatsi I, Ikaheimo M, Airaksinen J, and Takkunen J. Impaired left ventricular  diastolic function in athletes after utterly strenuous prolonged exercise. Int J Sports Med 8:61-65,1987. 40.  Niemela KO, Palatsi IJ, Ikaheimo MJ, Takkunen JT, and Vuori JJ. Evidence of impaired left  ventricular performance after an uninterrupted competitive 24 hour run. Circulation 70:350-356,1984. 41. Nozawa T, Cheng CP, Noda T, and Little WC. Effect of exercise on left ventricular mechanical efficiency in conscious dogs. Circulation 90:3047-3054,1994. 42. Nozawa T, Cheng CP, Noda T, and Little WC. Relation between left ventricular oxygen consumption and pressure-volume area in conscious dogs. Circulation 89:810-817,1994. 43.  O'Brien PJ, Shen H, Weiler J, lanuzzo CD, Wittnich C, Moe GW, and Armstrong PW.  Cardiac and muscle fatigue due to relative functional overload induced by excessive stimulation, hypersensitive excitation-contraction coupling, or diminished performance capacity correlates with sarcoplasmic reticulum failure. Can J Physiol Pharmacol 69:262-268,1991. 44.  Ohba H, Takada H, Musha H, Nagashima J, Mori N, Awaya T, Omiya K, and Murayama M.  Effects of prolonged strenuous exercise on plasma levels of atrial natriuretic peptide and brain natriuretic peptide in healthy men. Am Heart J141:751-758, 2001. 45.  O'Toole ML, Hiller DB, Crosby LO, and Douglas PS. The ultraendurance triathlete: a  physiological profile. Med Sci Sports Exerc 19: 45-50,1987. 46.  Palatini P, Bongiovi S, Macor F, Michieletto M, Mario L, Schiraldi C, and Pessina AC. Left  ventricular performance during prolonged exercise and early recovery in healthy subjects. Eur J Appl Physiol Occup Physiol 69:396-401, 1994. 47. Perrault H, Peronnet F, Lebeau R, and Nadeau RA. Echocardiographic assessment of left  ventricular performance before and after marathon running. Am Heart J112:1026-1031,1986. 48.  Rifai N, Douglas PS, O'Toole M, Rimm E, and Ginsburg GS. Cardiac troponin T and I,  echocardiographic [correction of electrocardiographic] wall motion analyses, and ejection fractions in athletes participating in the Hawaii Ironman Triathlon. Am J Cardiol 83:1085-1089,1999. 49. Rowe WJ. Endurance exercise and injury to the heart. Sports Med 16:73-79,1993. 50. Saltin B and Stenberg J. Circulatory Response to Prolonged Severe Exercise. J Appl Physiol 19: 833-838,1964. 51. Schaible TF and Scheuer J. Comparison of heart function in male and female rats. Basic Res Cardiol79:402-412,1984. 52.  Seals DR, Rogers MA, Hagberg JM, Yamamoto C, Cryer PE, and Ehsani AA. Left ventricular  dysfunction after prolonged strenuous exercise in healthy subjects. Am J Cardiol 61:875-879,1988. 53.  Stickland MK, Petersen SR, Haykowsky MJ, Taylor DA, and Jones RL. The effects of cycle  racing on pulmonary diffusion capacity and left ventricular systolic function. Respir Physiol Neurobiol 138: 291-299, 2003. 54.  Suman OE, Hasten D, Turner MJ, Rinder MR, Spina RJ, and Ehsani AA. Enhanced inotropic  response to dobutamine in strength-trained subjects with left ventricular hypertrophy. J Appl Physiol 88: 534-539, 2000. 55. Tibbits GF. Regulation of myocardial contractility in exhaustive exercise. Med Sci Sports Exerc 17:529-537,1985. 56.  Upton MT, Rerych SK, Roeback JR, Jr., Newman GE, Douglas JM, Jr., Wallace AG, and  Jones RH. Effect of brief and prolonged exercise on left ventricular function. Am J Cardiol 45:11541160,1980. 57.  Vanoverschelde JL, Younis LT, Melin JA, Vanbutsele R, Leclercq B, Robert AR, Cosyns  JR, and Detry JM. Prolonged exercise induces left ventricular dysfunction in healthy subjects. J Appl Physiol70:1356-1363,1991. 58.  Vatner DE, Vatner SF, Nejima J, Uemura N, Susanni EE, Hintze TH, and Homey CJ. Chronic  norepinephrine elicits desensitization by uncoupling the beta-receptor. J Clin Invest 84:1741-1748,1989.  28  59. Virmani R, Burke AP, Farb A, and Kark JA. Causes of sudden death in young and middleaged competitive athletes. Cardiol Clin 15:439-466,1997. 60.  Vizgirda VM, Wahler GM, Sondgeroth KL, Ziolo MT, and Schwertz DW. Mechanisms of sex  differences in rat cardiac myocyte response to beta-adrenergic stimulation. Am J Physiol Heart Circ Physiol 282: H256-263,2002. 61.  Warburton DE, Haykowsky MJ, Quinney HA, Blackmore D, Teo KK, Taylor DA, McGavock  J, and Humen DP. Blood volume expansion and cardiorespiratory function: effects of training modality. Med Sci Sports Exerc 36: 991-1000,2004. 62. Welsh RC, Warburton DE, Humen DP, Taylor DA, McGavock J, and Haykowsky MJ.  Prolonged Strenuous Exercise Alters the Cardiovascular Response to Dobutamine Stimulation. J Physiol, 2005. 63. Werle EO, Strobel G, and Weicker H. Decrease in rat cardiac beta 1- and beta 2-adrenoceptors by training and endurance exercise. Life Sci 46: 9-17,1990. 64.  White M, Yanowitz F, Gilbert EM, Larrabee P, O'Connell JB, Anderson JL, Renlund D,  Mealey P, Abraham WT, and Bristow MR. Role of beta-adrenergic receptor downregulation in the peak exercise response in patients with heart failure due to idiopathic dilated cardiomyopathy. Am J Cardiol 76:1271-1276,1995. 65.  Whyte GP, George K, Sharma S, Lumley S, Gates P, Prasad K, and McKenna WJ. Cardiac  fatigue following prolonged endurance exercise of differing distances. Med Sci Sports Exerc 32:10671072, 2000.  29  


Citation Scheme:


Usage Statistics

Country Views Downloads
United States 17 0
United Kingdom 3 0
China 2 2
Brazil 2 0
France 1 0
Japan 1 0
City Views Downloads
Washington 8 0
Unknown 6 6
Phoenix 2 0
Brasília 2 0
Shenzhen 2 2
Ashburn 2 0
Kirkby 2 0
Seattle 1 0
Tokyo 1 0

{[{ mDataHeader[type] }]} {[{ month[type] }]} {[{ tData[type] }]}
Download Stats



Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            async >
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:


Related Items