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Effect of lactic acid administration on rumen myoelectrical activity and pressure changes in the sheep Smith, Craig Michael 1978

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EFFECT OF LACTIC ACID ADMINISTRATION ON RUMEN MYOELECTRICAL ACTIVITY AND PRESSURE CHANGES IN THE SHEEP by Craig Michael Smith .Sc.(Agr.), University of B r i t i s h Columbia, 19 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in The Faculty of Graduate Studies (Department of Animal Science) We accept t h i s thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA October/ 197 8 ©Craig Michael Smith, 1978 In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f the r e -quirements f o r an advanced degree a t the U n i v e r s i t y o f B r i t i s h Columbia, I agree t h a t the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and study. I f u r t h e r agree t h a t p e r m i s s i o n f o r e x t e n s i v e copying of t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the Head of my Depart-ment or by h i s r e p r e s e n t a t i v e s . I t i s understood t h a t copy-ing or p u b l i c a t i o n of t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l not be allowed without my w r i t t e n p e r m i s s i o n . Department of Animal Science The U n i v e r s i t y o f B r i t i s h Columbia 2075 Wesbrook Pl a c e Vancouver, Canada V6T 1W5 C r a i g M i c h ael Smith i i ABSTRACT Pressure changes and m y o e l e c t r i c a l a c t i v i t y i n the ovine rumen were i n v e s t i g a t e d f o l l o w i n g the s u r g i c a l implan-t a t i o n of f l u i d f i l l e d b a l l o o n - t i p p e d tygon tubes and p a i r e d f i n e needle platinum e l e c t r o d e s . The c o r r e l a t i o n s among rumen pressure change and m y o e l e c t r i c a l s p i k e b u r s t d u r a t i o n , frequency and magnitude data from 447 7 one minute p e r i o d s were determined i n order to s e l e c t a s i n g l e r e l i a b l e q u a n t i -t a t i v e measurement of rumen m o t i l i t y . The r e s u l t s showed t h a t a l l these parameters a c c u r a t e l y r e f l e c t a c t i v i t y changes i n the rumen. M y o e l e c t r i c a l s p i k e b u r s t d u r a t i o n was shown to be the most s e n s i t i v e i n d i c a t o r and was used as the c r i -t e r i o n f o r examination of l a c t i c a c i d induced m o t i l i t y changes. Rumen m o t i l i t y was not a f f e c t e d by i n t r a r u m i n a l i n t r o -d u c t i o n of 1000 ml of 0.15 o r 0.7 M l a c t i c a c i d a t pH 2.0 v i a permanently implanted cannulae. Intravenous i n f u s i o n of 2 c o n c e n t r a t i o n s o f sodium l a c t a t e which i n c r e a s e d blood l a c t a t e l e v e l s by approximately 20 mg% and 180 mg% r e s p e c t i v e l y , a l s o had no e f f e c t on rumen m o t i l i t y . I n f u s i o n o f l a c t i c a c i d s o l u t i o n s (250 ml) 0.15 or 0.7 M (pH 2.0, 4.0 and 6.0) i n t r a d u o d e n a l l y v i a p o l y e t h y l e n e cannulae ex e r t e d profound e f f e c t s on rumen m o t i l i t y . Immedi-a t e l y f o l l o w i n g ( 1 min) the commencement of the i n f u s i o n of l a c t i c a c i d (pH 2.0), a s h o r t p e r i o d o f t o t a l i n h i b i t i o n o f m o t i l i t y o c c u r r e d which was f o l l o w e d by a r a p i d recovery of m o t i l i t y to near normal l e v e l s d e s p i t e the c o n t i n u a t i o n o f the i n f u s i o n . These i n i t i a l s h o r t p e r i o d s o f i n h i b i t i o n and recovery continued f o r up to one hour f o l l o w i n g termin-a t i o n of i n f u s i o n . S i m i l a r y e t somewhat reduced responses were observed upon i n t r a d u o d e n a l i n f u s i o n o f the l a c t i c a c i d s o l u t i o n s a t pH 4.0 and 6.0. These r e s u l t s suggest t h a t i n h i b i t i o n o f rumen m o t i l i t y i n l a c t i c a c i d o s i s may be caused p r i m a r i l y by l a c t i c a c i d produced i n the rumen e n t e r i n g the i n t e s t i n e and causing a s t i m u l a t i o n o f the e n t e r o g a s t r i c r e f l e x e s . TABLE OF CONTENTS ABSTRACT i i TABLE OF CONTENTS Vpf. LIST OF TABLES LIST OF FIGURES (vii LIST OF APPENDIX FIGURES - -ix ACKNOWLEDGEMENTS Ix INTRODUCTION 1 LITERATURE REVIEW 4 P r o p e r t i e s o f V i s c e r a l Smooth Muscle 4 C o n t r o l o f G a s t r o i n t e s t i n a l M o t i l i t y 7 G a s t r o i n t e s t i n a l Electromyography 15 A n a l y s i s of Electromyographic Data 16 Rumen S t a s i s A s s o c i a t e d with L a c t i c A c i d o s i s 18 MATERIALS AND METHODS 2 2 Animals 22 S u r g i c a l Procedures 22 i ) E l e c t r o d e s 22 i i ) B a l l o o n s 23 i i i ) Cannulae 23 M o n i t o r i n g o f M y o e l e c t r i c a l and Pressure Change A c t i v i t y 2 4 Determination of D i g e s t a pH 24 I n f u s i o n s 25 i ) Intraduodenal I n f u s i o n 25 i i ) I n t r a r u m i n a l I n f u s i o n 26 i i i ) Intravenous I n f u s i o n 26 A n a l y s i s of M y o e l e c t r i c a l and Pressure Change Data 26 i ) Measurement 26 i i ) A n a l y s i s 27 i i i ) P l o t s 27 RESULTS 2 8 pH of Duodenal D i g e s t a 28 P h y s i o l o g i c a l Recordings 28 C o r r e l a t i o n Among Rumen M o t i l i t y Parameters 31 I n f u s i o n Experiments 31 Intraduodenal A d m i n i s t r a t i o n of L a c t i c A c i d 31 i ) pH 2.0 31 i i ) pH 4.0 36 i i i ) pH 6.0 39 iv ) Intraduodenal S a l i n e 42 I n t r a r u m i n a l A d m i n i s t r a t i o n o f L a c t i c A c i d (pH 2.0) 44 Intravenous A d m i n i s t r a t i o n o f L a c t i c A c i d 44 i ) Sodium L a c t a t e 20 mg/ml 44 i i ) Sodium L a c t a t e 180 mg/ml 4 7 i i i ) S a l i n e 47 DISCUSSION 50 pH of Duodenal D i g e s t a 50 P h y s i o l o g i c a l Recordings 51 C o r r e l a t i o n s Among Rumen M o t i l i t y Parameters 52 Choice of Parameters f o r P l o t t i n g the Data 53 Intraduodenal A d m i n i s t r a t i o n of L a c t i c A c i d 55 Mode o f I n h i b i t o r y A c t i o n of Duodenal A c i d i f i c a t i o n 55 I n t r a r u m i n a l A d m i n i s t r a t i o n o f L a c t i c A c i d 65 Intravenous A d m i n i s t r a t i o n o f L a c t i c A c i d 66 SUMMARY AND CONCLUSIONS 68 BIBLIOGRAPHY 71 APPENDIX 84 vi LIST OF TABLES Table Page 1 pH of c o n s e c u t i v e duodenal d i g e s t a samples c o l l e c t e d from r e - e n t r a n t cannula 1 h a f t e r f e e d i n g on 5 d i f f e r e n t days 29 2 C o r r e l a t i o n s among rumen m y o e l e c t r i c a l parameters 34 LIST OF FIGURES Figure Page 1 Simultaneously recorded rumen pressure changes and myoelectrical a c t i v i t y 30 2 E f f e c t of duodenal infusion of 0.15 M l a c t i c acid (pH 2.0) on simultaneously re-corded rumen pressure changes and myo-e l e c t r i c a l a c t i v i t y 32 3 Experiment 1. E f f e c t of intraduodenal infusion of 0.15 M l a c t i c acid (pH 2.0) on rumen spike burst duration (animal #1) 35 4 Experiment 18. E f f e c t of intraduodenal infusion of 0.15 M l a c t i c acid (pH 4.0) on rumen spike burst duration (animal #1). 37 5 Experiment 19. E f f e c t of intraduodenal infusion of 0.15 M l a c t i c acid (pH 4.0) on rumen spike burst duration (animal #1). 38 6 Experiment 20. E f f e c t of intraduodenal infusion of 0.7 M l a c t i c acid (pH 4.0) on rumen spike burst duration (animal #1) 40 7 Experiment 21. E f f e c t of intraduodenal infusion of 0.7 M l a c t i c acid (pH 4.0) on rumen spike burst duration (animal #3) 41 8 Experiment 26. E f f e c t of intraduodenal infusion of physiological saline on rumen spike burst duration (animal #3) 43 9 Experiment 34. E f f e c t of intraruminal infusion of 0.7 M l a c t i c acid (pH 2.0) on rumen spike burst duration (animal #3) 45 10 Experiment 38. E f f e c t of intravenous infusion of sodium lactate (20 mg/ml) on rumen spike burst duration (animal #3) 46 Experiment 39. E f f e c t of intravenous i n -f u s i o n of sodium l a c t a t e (180 mg/ml) on rumen sp i k e b u r s t d u r a t i o n (animal #3) LIST OF APPENDIX FIGURES Animal P r e p a r a t i o n s E f f e c t s of Intraduodenal, I n t r a r u m i n a l and Intravenous L a c t i c A c i d I n f u s i o n on Rumen Spike B u r s t D u r a t i o n ACKNOWLEDGEMENTS I would l i k e to express my s i n c e r e g r a t i t u d e to Dr. C. R. Krishnamurti f o r h i s guidance, suggestions and unending enthusiasm throughout t h i s t h e s i s . I would a l s o l i k e to ex-press my thanks to the f a c u l t y members o f the Department of Animal Science f o r t h e i r c o n t r i b u t i o n s to the development of t h i s p r o j e c t and to.Mr. David K i t t s and Mr. Bob P r a t t f o r t h e i r h elp i n the s u r g i c a l procedures. S p e c i a l thanks are extended to Mr. Duncan J e f f r i e s f o r h i s e x p e r t i s e i n the computer a n a l y s i s of the data and to Miss P a t r i c i a Davis f o r the t e c h n i c a l a s s i s t a n c e p r o v i d e d . 1 INTRODUCTION Rumen atony a s s o c i a t e d with acute l a c t i c a c i d o s i s i n g r a i n engorged sheep and c a t t l e has been a t t r i b u t e d to a num-ber of f a c t o r s . Juhasz and Szegedi (1968) have r e p o r t e d t h a t as rumen l a c t i c a c i d c o n c e n t r a t i o n i n c r e a s e d and pH dropped, the amplitude and frequency of rumen pressure changes dimin-i s h e d . T h i s i n h i b i t o r y a c t i o n i s not a d i r e c t e f f e c t of the a c i d on the rumen w a l l (Ash, 19 59). However, Dunlop (1961) showed t h a t i n t r a r u m i n a l i n t r o d u c t i o n o f .5 to .7 M l a c t i c a c i d s o l u t i o n s induced rumen s t a s i s . S o l u t i o n s c o n t a i n i n g a c e t a t e , p r o p ionate and b u t y r a t e i n f u s e d i n t r a r u m i n a l l y have been shown to i n h i b i t rumen m o t i l i t y ( S h i n o z a k i , 1958). These r e s u l t s c o u l d not be repeated by Pearce (1965). Svendsen (1973) found t h a t severe i n h i b i t i o n of rumen m o t i l i t y o c c u r r e d f o l l o w i n g i n f u s i o n s of v o l a t i l e f a t t y a c i d s (VFA) to a rumen c o n c e n t r a t i o n between 5 and 10 mM u n d i s s o c i a t e d VFA. The pH of the d i g e s t a was not shown to e x e r t a d i r e c t i n h i b i t o r y e f f e c t . I n f u s i o n o f l a c t i c a c i d i n t o the proximal duodenum i n sheep caused a marked i n h i b i t i o n o f rumen pressure changes i n d i c a t i n g t h a t the small i n t e s t i n e may p l a y a major r o l e i n the g e n e r a t i o n of rumen atony i n l a c t i c a c i d o s i s (Bruce and Huber, 1973). Intravenous i n f u s i o n o f a c e t i c , p r o p i o n i c and b u t y r i c a c i d s has been shown to cause immediate i n h i b i -t i o n o f rumen m o t i l i t y as w e l l as a l t e r j e j u n a l m y o e l e c t r i c a l a c t i v i t y (Bueno and Ruckebusch, 1976). L a c t i c a c i d i s ab-sorbed from the rumen and i n t e s t i n e r e s u l t i n g i n hig h blood 2 l a c t a t e l e v e l s i n animals s u f f e r i n g from the d i s e a s e (Dunlop, 1972). However, to the author's knowledge no work has been done as to the e f f e c t t h i s might have on rumen m o t i l i t y . T o x i c compounds o f ruminal o r i g i n have a l s o been i m p l i c a t e d as c a u s a t i v e f a c t o r s of gut s t a s i s . I t has been shown t h a t i n g r a i n engorged sheep and c a t t l e , dead Gram negative bac-t e r i a r e l e a s e a l i p o p o l y s a c c h a r i d e endotoxin which causes a number of c i r c u l a t o r y and h e m a t o l o g i c a l e f f e c t s and a v e r y marked i n h i b i t i o n o f rumen m o t i l i t y . Though the involvement o f histamine i n l a c t i c a c i d o s i s has been s t u d i e d by many workers, the f a i l u r e t o d e t e c t s i g n i f i c a n t q u a n t i t i e s o f t h i s amine i n rumen f l u i d on a time course c o r r e s p o n d i n g to the i n h i b i t i o n of rumen m o t i l i t y l eaves i t s r o l e open to q u e s t i o n . Although the g e n e r a l decrease i n rumen pH i n g r a i n en-gorged animals i s due to the accumulation o f h i g h concentra-t i o n s o f l a c t i c a c i d , the i n i t i a l drop i n pH i s r e p o r t e d to r e s u l t from an i n c r e a s e i n v o l a t i l e f a t t y a c i d p r o d u c t i o n (Dirksen, 1970). In view of the s i g n i f i c a n t r o l e of l a c t i c a c i d i n the e t i o l o g y of rumen o v e r l o a d , the o b j e c t i v e s of t h i s study were to develop r e l i a b l e techniques f o r the q u a n t i t a t i v e measure-ment o f rumen atony and to e l u c i d a t e the mechanisms whereby l a c t i c a c i d induces t h i s phenomenon i n sheep. The d i r e c t e f f e c t o f l a c t i c a c i d on the rumen v i s c u s was t e s t e d by i n -f u s i n g v a r i o u s c o n c e n t r a t i o n s of l a c t i c a c i d i n t o the rumen v i a permanently implanted cannulae. The p o s s i b i l i t y t h a t the i n t e s t i n e may generate rumen i n h i b i t o r y responses was examined by the i n t r o d u c t i o n o f l a c t i c a c i d i n t o the p r o x i mal duodenum. L a s t l y , the p o s s i b i l i t y o f blood l a c t a t e i n duced rumen m o t i l i t y i n h i b i t i o n was a l s o i n v e s t i g a t e d . 4 ~\ LITERATURE REVIEW P r o p e r t i e s of V i s c e r a l Smooth Muscle Movement o f d i g e s t a through the ruminant d i g e s t i v e t r a c t i s the r e s u l t o f a c o o r d i n a t e d s e r i e s of v i s c e r a l smooth mus-c l e c o n t r a c t i o n s . These events are mediated by n e u r a l and hormonal mechanisms, the i n t e r r e l a t i o n s h i p s of which have not as y e t been f u l l y e l u c i d a t e d . U n l i k e s t r i a t e d s k e l e t a l muscle, v i s c e r a l smooth muscle i s composed o f i n d i v i d u a l u n i n u c l e a r c e l l s and i s under the i n v o l u n t a r y c o n t r o l o f the autonomic nervous system. The f u s i f o r m shaped c e l l s are approximately .2 mm i n l e n g t h , 5 ym i n diameter and are o f f s e t such t h a t the broad middle n u c l e a r r e g i o n o f one c e l l l i e s o p p o s i t e the narrow tapered end o f an adjacent c e l l (Bloom and Fawcett, 1975). The c e l l s e x h i b i t an amorphous sarcoplasm i n which the c o n t r a c t i l e p r o t e i n s a c t i n and myosin are d i f f u s e l y o r i e n t e d . T h i s arrangement c o n t r a s t s d i r e c t l y w i t h s k e l e t a l muscle i n which the c o n t r a c t i l e pro-t e i n s are or g a n i z e d i n a s p e c i f i c c o n f i g u r a t i o n , the r e s u l t o f which i s the formation o f dark and l i g h t bands i n the muscle f i b r e . Two p r o t e i n f i l a m e n t types are apparent i n smooth muscle c r o s s s e c t i o n s seen under the e l e c t r o n micro-scope. The t h i n f i l a m e n t s (30°A dia) are thought t o be a c t i n whereas the t h i c k f i l a m e n t s (80°A dia) are b e l i e v e d to be myosin molecules t h a t have org a n i z e d i n t o f i l a m e n t com-plexes a t the moment of e x c i t a t i o n - c o n t r a c t i o n c o u p l i n g (Devine and Somlyo, 19 71). 5 Smooth muscle may be induced to c o n t r a c t by a number of s t i m u l i which can be c a t e g o r i z e d i n t o two groups. E x c i t a t i o n -c o n t r a c t i o n c o u p l i n g t h a t r e s u l t s from e l e c t r i c a l change i n the muscle c e l l membrane i s r e f e r r e d to as e l e c t r o m e c h a n i c a l c o u p l i n g . E x c i t a t i o n - c o n t r a c t i o n c o u p l i n g induced by changes i n i n t r a c e l l u l a r pH, c y c l i c n u c l e o t i d e c o n c e n t r a t i o n s , i n t r a -c e l l u l a r Ca++ c o n c e n t r a t i o n , e t c . , a l l o f which may be i n -f l u e n c e d by n e u r o t r a n s m i t t e r s or drugs i s termed pharmaco-mechanical c o u p l i n g (Somlyo and Somlyo, 1968). Gut smooth muscle i s unique i n t h a t not o n l y does i t e x h i b i t the normal c e l l membrane d e p o l a r i z a t i o n - r e p o l a r i z a t i o n s p i k e response found i n other smooth muscle, s k e l e t a l and c a r d i a c muscle types but a l s o undergoes a spontaneously gener-ated slow rhythmic 8-10 mV d e p o l a r i z a t i o n - r e p o l a r i z a t i o n which has been termed E l e c t r i c a l C o n t r o l A c t i v i t y (ECA) (Sarna, 1975; D a n i e l and Irwin, 1968). Superimposed on the peak of t h i s continuous waveform may be f u r t h e r r a p i d s p i k e p o t e n t i a l s t h a t a t maximum d e p o l a r i z a t i o n r e s u l t i n a membrane p o t e n t i a l of -10 to 0 mV (Guyton, 1976a). These spike b u r s t s have a l s o been termed E l e c t r i c a l Response A c t i v i t y (Sarna, 1975) and depending on the stimulus r e s u l t s from pharmaco or e l e c t r o m e c h a n i c a l c o u p l i n g . The c e l l u l a r mechanism f o r the g e n e r a t i o n o f ECA i s s t i l l somewhat u n c l e a r . The f i r s t theory proposed by D a n i e l and Chapman (1963) was t h a t a simple Na+ pump "turned o f f " , the r e s u l t being t h a t the i n f l u x of Na+ ions i n t o the c e l l caused membrane d e p o l a r i z a t i o n . R e p o l a r i z a t i o n was thought 6 to be e f f e c t e d by a " t u r n i n g on" o f the Na+ pump. T h i s model however f a i l e d to e x p l a i n some governing f a c t o r s , such as the involvement of membrane sodium conductance (gNa) v a r i a -t i o n or the b a s i s f o r the continuous p o t e n t i a l o s c i l l a t i o n . I t was then proposed t h a t a b u i l d u p i n ATP c o n c e n t r a t i o n t r i g g e r e d an i n c r e a s e i n gNa which leads to the d e p o l a r i z a -t i o n phase of the c o n t r o l p o t e n t i a l (Job, 1969) . The inward leak o f Na+ and thus i n c r e a s e i n i n t r a c e l l u l a r Na+ conc e n t r a -t i o n , t r i g g e r s the Na+ pump e v e n t u a l l y d e p l e t i n g the ATP s t o r e s t o su b t h r e s h o l d l e v e l s . T h i s would cause a decrease i n gNa r e s u l t i n g i n r e p o l a r i z a t i o n and c o n t i n u a t i o n o f the o s c i l l a t o r y mechanism. T h i s theory, although a t t r a c t i v e , f a i l e d t o e x p l a i n some of the notched ECA t r a c i n g s from simple smooth muscle c e l l s and the dependence of d e p o l a r i z a -t i o n of CI i o n s . The theory proposed by El-Sharkawy and D a n i e l (1973) e x p l a i n s t h a t the i n i t i a l d e p o l a r i z a t i o n r e -s u l t s from a c a l c i u m dependent t r a n s i e n t i n c r e a s e i n gNa fol l o w e d by an i n h i b i t i o n o f an inward d i r e c t e d c h l o r i d e pump. The t r i g g e r f o r r e p o l a r i z a t i o n i s not c l e a r l y under-stood. The ECA i s generated i n the l o n g i t u d i n a l muscle of the gut and passes to the c i r c u l a r muscle p o s s i b l y v i a t h i n c o n n e c t i n g muscle strands ( B o r t o f f , 1961; Ruckebusch, 1970; Connor e t aJL. , 1977) . Although the ECA a r i s e s from a continuous d e p o l a r i z a -t i o n - r e p o l a r i z a t i o n , i t does not i n d i c a t e e x c i t a t i o n -7 contraction coupling. Only the spike bursts that are gen-erated by some of these waves are associated with muscular contraction (Milton et a l . , 1955; Prosser, 1973). Control of Gastrointestinal M o t i l i t y The g a s t r o i n t e s t i n a l (Gl) t r a c t i s under e x t r i n s i c nervous control, involving various receptor types, a r e f l e x center and efferent autonomic nerves (Thomas and Baldwin, 1968). Though no s p e c i f i c anatomical structures have been i d e n t i f i e d i n the mucosa of the Gl t r a c t similar to those found i n the skin or a r t e r i e s , i t has been generally accepted that a variety of receptor types are present (Thomas and Baldwin, 1968; Weisbrodt, 1977; Davenport, 19 77). In a de-t a i l e d review on the control of g a s t r i c emptying and m o t i l i t y , Cooke (1975) discussed the evidence for the existence of these receptors and the roles they presumably play i n gut homeostasis. It has been shown by many workers and discussed i n a review by Hunt and Knox (196 8a) that entry of acid into the duodenum causes a decrease i n g a s t r i c emptying. Test meals of nine acids i n human subjects have shown that as the concentration of t i t r a t a b l e acid increased, the delay i n gastric emptying increased (Hunt and Knox, 1969). It was also shown that there was a r e c t i l i n e a r r e l a t i o n s h i p between the mean acid concentration required for a recovery of 450 ml 8 of the t e s t meal and the square r o o t of the molecular weight of the a c i d . The a c i d s o f low molecular weight were the most e f f e c t i v e i n i n h i b i t i n g g a s t r i c emptying of the t e s t meal. I t has been shown t h a t t h i s g a s t r i c i n h i b i t o r y r e f l e x i s an extremely s e n s i t i v e and r a p i d c o n t r o l l i n g mechanism (Cooke, 1974). Although t h i s study d i d not d i s t i n g u i s h between n e u r a l or hormonal pathways, the r a p i d i t y w i t h which the e f f e c t s are produced (1 min.) suggests a n e u r a l mechanism (Cooke, 19 75). Experiments by Andrews and Andrews (1971) have shown t h a t as a c i d i s i n t r o d u c e d i n t o the r a b b i t i n t e s t i n e , the num-ber of a f f e r e n t mesenteric nerve impulses i n c r e a s e d s i g n i f i -c a n t l y . They noted two temporally separate responses and suggested the e x i s t e n c e o f two types o f nerve r e c e p t o r s i n the i n t e s t i n e . Iggo (1957) has shown t h a t a c i d r e c e p t o r s e x i s t i n the w a l l of the f e l i n e stomach t h a t e x h i b i t a stimu-l a t o r y t h r e s h o l d of pH 3 or lower. S i m u l a t i o n o f osmotic r e c e p t o r s (Hunt and Pathek, 1960; Meeroff e t a l . , 1974; Meeroff e t a l . , 1975; Mostaghni and Howard, 1975), t e n s i o n and p r e s s u r e r e c e p t o r s (Iggo, 1955; P a i n t a l , 1954; Hukuhara e t a l . , 1959; Leek, 1972), f a t recep-t o r s (Quigley and Meschan, 1941; Menguy, 1960; Hunt and Knox, 1968b) and amino a c i d r e c e p t o r s (Thomas, 1942; Cooke and Moulang, 19 72; Stephens and Cooke, 1972) have a n e g a t i v e f e e d -back on the g a s t r i c musculature. Consequently, as the stimu-l u s i n c r e a s e s i n magnitude t h e r e i s an i n h i b i t i o n of g a s t r i c 9 emptying. In r e l a t i v e terms the f a t r e c e p t o r s are the most s e n s i t i v e w h i le the osmoreceptors are the l e a s t s e n s i t i v e ones. For example, to i n i t i a t e s i g n i f i c a n t i n h i b i t i o n of g a s t r i c emptying a lower c o n c e n t r a t i o n of m y r i s t i c a c i d (8 mM) i s as equipotent as HCI (50 mM) or glucose (500 mM) (Hunt and Knox, 196 8a). The storhach of - ruminants,, e x h i b i t s simLliar;responses to t e n s i o n , s t r e t c h and pH but d e s p i t e determined anatomical s u r -veys, no s p e c i f i c s t r u c t u r e s have been demonstrated (Habel, 1956; Comline and Message, 1965). I t has been shown t h a t i n a d d i t i o n t o the abomasal fundus, p y l o r u s and the duodenum, the r e t i c u l o r u m e n i s a l s o s e n s i t i v e to a c i d and a l k a l i by r a p i d l y adapting mechanoreceptors (Harding and Leek, 1972a; Harding and Leek, 1972b). In an e x t e n s i v e review, Leek and Harding (1975) d i s c u s s e d the evidence f o r the presence of these r e c e p t o r s and the s t i m u l i which t r i g g e r a f f e r e n t nerve impulses from the a c i d , t e n s i o n and s t r e t c h r e c e p t o r s l o c a t e d i n the ruminant d i g e s t i v e t r a c t . Much knowledge has been gained from the work done on the c e n t r a l nervous system and i t s involvement i n the r e g u l a -t i o n o f g a s t r i c m o t i l i t y . B e l l and Lawn (1955) have l o c a l -i z e d an area of the b r a i n stem w i t h i n .the l i m i t s 6 mm cephalad to 2 mm caudad to the obex i n the medulla oblongata t h a t i s i n v o l v e d with the n e u r a l c o n t r o l of the r e t i c u l u m , rumen and esophagus. A review by Thomas and Baldwin (1968) summarizes much of the e a r l y l i t e r a t u r e and more r e c e n t work i s reviewed 10 by Leek and Harding (1975). The neuroanatomy of the ruminant stomach has been studied i n a comprehensive review by Comline et a l . (1968). Gastrointestinal myoelectrical a c t i v i t y i s modulated by a wide variety of mechanisms which act d i f f e r e n t l y on various areas of the gut. There i s also a great deal of functional v a r i a t i o n among d i f f e r e n t species. Neural control i s effected by the autonomic nervous system. The parasympa-th e t i c f i b r e s greatly influence the m o t i l i t y of the digestive t r a c t (Titchen, 1968; Thomas and Baldwin, 1968; Guyton, 1976b). The ECA, although generated spontaneously by the smooth muscle i s affected by extensive nervous stimulation. It has been shown that the vagus contains acid and gastrin-releasing f i b r e s (Pritchard et a_l. , 1968), g a s t r o i n t e s t i n a l motor accel-eratory and i n h i b i t o r y f i b r e s (Sarna and Daniel, 1975; Martinson, 1975) and afferent sensory f i b r e s (Paintal, 1973). Thus the ablation or stimulation of t h i s nerve would be ex-pected to have a marked e f f e c t on gut m o t i l i t y . Electrostim-ulation of the Latarjet (antral vagal branch) resulted i n near immediate contraction of canine gastric smooth muscle (Sarna and Daniel, 1975). Burnstock (1972) has shown that the transmitter substance of vagal motor i n h i b i t o r y f i b r e s i s ATP or a related nucleotide and these f i b r e s have been termed purinergic. Vagotomy (Duncan, 1953) or atropine administration (Duncan, 1954) results i n the i n h i b i t i o n of orderly ruminoreticular contractions. Severing the nerves which accompany the l e f t ruminal artery has a similar 11 e f f e c t , thus i n d i c a t i n g the l a r g e c o n t r o l component o f ex-t r i n s i c nerves (Ruckebusch, 1970). The r o l e of the sympathetic nervous system i n c o n t r o l of gut m o t i l i t y i s s t i l l as y e t unresolved. There i s some doubt as to whether the sympathetic nerves a c t u a l l y a c t d i r e c t l y at the v i s c e r a l smooth muscle. Norberg and Hamberger (1964) and S c h o f i e l d (1962) have shown t h a t the a d r e n e r g i c neurons of the gut synapse w i t h the i n t r a m u r a l ground plexus o f the v i s c e r a l blood v e s s e l s and not with the v i s c e r a l mus-c l e . I t has been suggested t h a t catecholamines reach the v i s c e r a l smooth muscle not by d i r e c t i n n e r v a t i o n but by d i f f u s i o n from s i t e s i n n e r v a t i n g the blood v e s s e l s i n the gut w a l l (Celander, 1959; Koch, 1959). Thus the sympathetic-a l l y mediated i n h i b i t i o n o f gut m o t i l i t y i s c o n s i d e r e d to be an i n d i r e c t one, o c c u r i n g 20-40 seconds a f t e r i n t e s t i n a l v a s o c o n s t r i c t i o n r e s u l t i n g from sympathetic f i b r e s t i m u l a t i o n . T h i s i s caused by the d i f f u s i o n o f the v a s o a c t i v e c a t e c h o l a -mines to the gut muscle (Davenport, 1977). Martinson (1975) suggested t h a t the sympathetic a d r e n e r g i c f i b r e s p l a y an i n -s i g n i f i c a n t r o l e i n the c o n t r o l of g a s t r i c m o t i l i t y and t h a t the nervous c o n t r o l i s by the c h o l i n e r g i c e f f e r e n t s t i m u l a -t o r y and the p u r i n e r g i c i n h i b i t o r y f i b r e s . The presence o f a d r e n e r g i c f i b r e s synapsing a t the g a n g l i o n i c l e v e l ( S c h o f i e l d , 1962) suggests t h a t the a d r e n e r g i c c o n t r o l of g a s t r i c m o t i l i t y i s one o f b l o c k i n g e x c i t a t o r y a c t i v i t y i n the i n t r i n s i c system or of v a g a l nerves (Jansson, 19 69). 12 Svendsen (1973) s t a t e d i n h i s e x t e n s i v e review t h a t the sympathetic nervous system i s of l i t t l e importance i n the c o n t r o l of ruminant m o t i l i t y . Supportive of t h i s statement i s the work of LeBars e t a l . (1953) and Kay (1959) who showed t h a t splanchnotomy has no s i g n i f i c a n t e f f e c t on the ruminant gut. A d e t a i l e d study of Semba and Hiraoka (1957) showed t h a t upon weak e l e c t r i c a l s t i m u l a t i o n o f s p l a n c h n i c nerve f i b r e s a s t i m u l a t i o n of g a s t r i c smooth muscle r e s u l t e d . A s t r o n g e r e l e c t r i c a l s t i m u l i however r e s u l t e d i n an i n h i b i t i o n of muscle c o n t r a c t i o n . In t h e i r review of g a s t r i c m o t i l i t y , Thomas and Baldwin (1968) conclude from t h i s and o l d e r works by Babkin e t aJL. (1939) and Kure and F u j i i (1933) t h a t there are two types of f i b r e s i n the v i s c e r a l sympathetic nerve trunk, low t h r e s h o l d c h o l i n e r g i c e x c i t a t o r y f i b r e s and h i g h t h r e s h o l d a d r e n e r g i c i n h i b i t o r y f i b r e s . The primary mediator o f g a s t r i c emptying and m o t i l i t y i s the e n t e r o g a s t r i c r e f l e x (Cooke, 1975; Guyton, 1976b). The s t i m u l i shown to e l i c i t an i n h i b i t o r y response i n g a s t r i c emptying f a i l to do so upon vagotomy (Thomas and Baldwin, 1968; Knoebel, 1971). The myenteric plexus (Guyton, 1976b) and c e l i a c and s u p e r i o r mesenteric g a n g l i a (Schapiro and Woodward, 1959) are a l s o b e l i e v e d to p l a y a major r o l e i n the e n t e r o g a s t r i c r e f l e x . Cooke and C l a r k e (1976) found t h a t i n j e c t i o n o f guanethidine and r e s p e r i n e (drugs t h a t d e p l e t e the a d r e n e r g i c nerve t e r m i n a l s of norepinephrine) i n t o dogs f e d an a c i d meal, i n c r e a s e d g a s t r i c emptying. 1 3 T h i s i n d i c a t e d t h a t the i n h i b i t o r y e f f e c t on g a s t r i c m o t i l i t y was a d r e n e r g i c . However, when the a and 3 b l o c k e r s pro-p r a n o l o l and phentolamine were i n j e c t e d , no e f f e c t on the g a s t r i c i n h i b i t o r y mechanism was found. Thus they concluded t h a t the a d r e n e r g i c i n h i b i t o r y mechanism i s n e i t h e r a or 3 r e c e p t o r mediated. They proposed t h a t c h o l i n e r g i c a c t i v i t y s t i m u l a t e s g a s t r i c emptying and t h a t t h i s a d r e n e r g i c r e f l e x i n i t i a t e s a slowing e f f e c t . The degree to which the myenter-i c or mucosal nerve p l e x i i n the w a l l o f the i n t e s t i n e a f f e c t the motor a c t i v i t y of the stomach i s unknown p r i m a r i l y because of the nature o f t h e i r l o c a t i o n i n the gut w a l l (Martinson, 1975) which makes i t d i f f i c u l t t o study them under i n v i v o c o n d i t i o n s . The e n t e r o g a s t r i e r e f l e x a l s o has a very l a r g e hormonal component (Guyton, 1976). However i t i s d i f f i c u l t to d i f -f e r e n t i a t e the n e u r a l from the humoral component because the t a r g e t organ becomes l e s s s e n s i t i v e to hormonal a c t i o n upon a b l a t i o n of the n e u r a l i n f l u e n c e s (Cooke, 1975). T h i s s i t u a -t i o n combined wi t h the f a c t t h a t the e n t e r o g a s t r i c hormones are not produced by d i s c r e t e organs which can be i s o l a t e d or removed, has made the i n v e s t i g a t i o n of the e n t e r o g a s t r i c r e -f l e x d i f f i c u l t . F u r t h e r c o m p l i c a t i n g the problem i s the presence i n the Gl t r a c t o f at l e a s t f o u r t e e n d i f f e r e n t hor-mones having some e f f e c t on gut m o t i l i t y . T h e i r r o l e and i n t e r r e l a t i o n s h i p s under p h y s i o l o g i c a l c o n d i t i o n s are not f u l l y understood. G a s t r i n , a p o l y p e p t i d e hormone r e l e a s e d by food, s t r e t c h 14 or a l k a l i i s r e l e a s e d from the a n t r a l mucosa and a f f e c t s not o n l y g a s t r i c a c i d s e c r e t i o n but has a marked s t i m u l a t o r y e f f e c t on motor f u n c t i o n of the stomach, sma l l i n t e s t i n e and c o l o n (Makhlouf, 1974; Grossman, 1974). M o t i l i n , a 22 amino a c i d p e p t i d e o r i g i n a l l y e x t r a c t e d from p o r c i n e duodenum has v a r y i n g e f f e c t s i n d i f f e r e n t s p e c i e s . In dogs i t i s r e l e a s e d by a l k y l a t i o n of the duodenum and s t i m u l a t e s g a s t r i c emptying (Brown e t a l . , 1971). In man, however, the s e c r e -tagogue i s i n t r a d u o d e n a l a c i d which r e s u l t s i n an i n h i b i t i o n of g a s t r i c emptying (Mitznegg e t a l . , 1976). The e f f e c t of m o t i l i n on ruminant G l m o t i l i t y has not been i n v e s t i g a t e d . C h o l e c y s t o k i n - p a n c r e o z i m i n (CCK-PZ), s e c r e t i n , g a s t r i c i n -h i b i t o r y p o l y p e p t i d e (GIP), and bulbogastrone are r e l e a s e d from the duodenum by a c i d e n t e r i n g the i n t e s t i n e and have profound e f f e c t s on G l m o t i l i t y (Makhlouf, 1974; Grossman, 1974; Anderson, 1974; Cooke, 1975). Other hormones known to have G l motor e f f e c t s are v a s o a c t i v e i n t e s t i n a l p o l y -peptide (VIP) (Said and Makhlouf, 1974), i n s u l i n i n dog and sheep jejunum (Bueno and Ruckebusch, 1976) , enteroglucagen (Pearse et a l . , 1977), p r o s t a g l a n d i n s (Milton-Thompson et a l . , 1973), substance P (Grubb and Burks, 1978), c o h e r i n ( H i a t t e t a l . , 1973), bombesin ( B e r t a c c i n i e t a l . , 1973) and som a t o s t a t i n (Bloom e t a_l. , 1974). Experiments have been conducted on the e f f e c t o f the gut hormones g a s t r i n and s e c r e t i n on ruminant G l m o t i l i t y . These hormones markedly reduced the v i s c e r a l electromyo-g r a p h i c a c t i v i t y and g a s t r i c emptying (Bruce and Huber, 1973; 15 McLeary and T i t c h e n , 1975; Ruckebusch, 1971; B e l l e t a l . , 1977) . G a s t r o i n t e s t i n a l Electromyography The use of electromyography as a t o o l f o r i n v e s t i g a -t i o n of s k e l e t a l muscle a c t i v i t y was f i r s t d i s c o v e r e d by M a t t e u c c i i n 1844, but was not used f o r v i s c e r a l smooth mus-c l e s t u d i e s u n t i l r e c e n t l y . Most knowledge of ruminant g a s t r o i n t e s t i n a l m o t i l i t y has been o b t a i n e d by other methods i n c l u d i n g the use o f dyes and markers f o r o b s e r v i n g d i g e s t a passage (Hogan, 1964), open-tipped or b a l l o o n - t i p p e d cathe-t e r s f o r o b s e r v i n g i n t r a l u m i n a l p r e s s u r e changes (Coombe, 1966; Leek and U l l a h , 1967). The f i r s t comprehensive study of ruminant v i s c e r a l electromyography was done by Ruckebusch i n 1970. T h i s de-t a i l e d work u t i l i z e d p a i r e d f i n e (120 u d i a . ) nichrome wire e l e c t r o d e s i n s e r t e d on the s e r o s a l s u r f a c e a t v a r i o u s l o c a -t i o n s on the d i g e s t i v e t r a c t . The s i g n a l generated was then recorded by a pen o s c i l l o g r a p h . E l e c t r o d e s o f t h i s type pioneered by Basmajian and Stecko (1962) are p r e f e r r e d as they can be c h r o n i c a l l y implanted with minimal t i s s u e damage and g i v e a c l e a r sharp s i g n a l (Basmajian, 1974). The advantages of u t i l i z i n g electromyography as a para-meter of gut m o t i l i t y are t h a t i t i s s e n s i t i v e to changes'in a c t i v i t y and i s l o c a l i z e d t o the area under study and not 16 confounded by a c t i v i t y i n other organs such as i s the case with p r e s s u r e readings (Ruckebusch, 1970). With the advent o f t h i s technique, much i n s i g h t has been gained on the type of a c t i v i t y o c c u r r i n g i n v a r i o u s r e g i o n s of the ruminant G l t r a c t ( G r i v e l and Ruckebusch, 1972; G r i v e l , 1972; Ruckebusch and Bueno, 1977; Bueno and Ruckebusch, 19 74) i n response to f e e d i n g (Ruckebusch and Bueno, 19 75; Ruckebusch and Bueno, 1976), hormones (Pass and Heath, 1978; McLeary and T i t c h e n , 1975; B e l l e t a l . , 1977; Ruckebusch, 1971; Bruce and Huber, 1973) and to drugs (Pass and Heath, 1978; Ruckebusch, 1977). A n a l y s i s of Electromyographic Data S e v e r a l techniques have been d e v i s e d f o r a n a l y s i s o f the electromyographic data produced by t h i s type of study. O r i g i n a l l y Ruckebusch (1970) simply presented the data as obtained and v i s u a l l y r e l a t e d the s p i k e b u r s t i n g ERA to the pressure changes. Some s t u d i e s may continue f o r s e v e r a l hours ( G r i v e l and Ruckebusch, 1972; Ruckebusch and Bueno, 1976; Ruckebusch, 1977), making t h i s type of data unwieldy, p a r t i c u l a r l y so i f one wishes to study i n h i b i t o r s or stimu-l a t o r s of c o n t r a c t i o n s t r e n g t h and frequency. T h i s s t i m u l a t e d the development of a f a r more s o p h i s -t i c a t e d technique whereby the polygraph was connected to a magnetic tape r e c o r d e r and the data analysed by a two l i n e i n t e g r a t o r (Ruckebusch and Tomov, 1973). Oigaard and Dorph 17 (1974a) examined a l l possible combinations of correlations between one thousand corresponding pairs of spike potentials and pressure waves. They found a high degree of c o r r e l a t i o n between duration and frequency of pressure change related spike bursts. Thus the value of electromyography as a quan-t i t a t i v e measure of gut a c t i v i t y was established. These workers have also developed a method whereby data can be transposed to a concise chart or to punch cards represen-tin g an ultrashort summary of the recorded spike bursts (Oigaard and Dorph, 1974b). On the other hand, ECA i s not considered to be of any p r a c t i c a l use for quantitative analysis of mo-t i l i t y recordings (Oigaard et. a l . , 1975). The ECA does not r e f l e c t contraction of the v i s c e r a l muscle of variations i n m o t i l i t y . Stemper and Cooke (1975) developed a simple method of data analysis with s t r a i n gauges. The number of v i s c e r a l muscle contractions detected each minute were summed and a m o t i l i t y index was determined. The peak height of a l l con-tractions i n each one minute period was t o t a l l e d and a cumu-l a t i v e index was calculated by adding the consecutive indices. Hirose et 'al. (1975) u t i l i z e d a general purpose com-puter for analysis of electromyographic data under normal and pathological conditions. The frequency, amplitude and a number of other parameters of s k e l e t a l muscle were determined enabling i d e n t i f i c a t i o n of diseased tissue. Techniques of t h i s nature have been reviewed extensively by Basmajian et a l . (1975). 18 P o s t a i r e e t a l . (1976) u t i l i z e d a computer a n a l y s i s o f electromyograms and pr e s s u r e a c t i v i t y o f r a t c o l o n t o q u a n t i -f y p e r i o d i c components from a n o i s y s i g n a l t h a t are u n n o t i c e -a b l e by v i s u a l examination. Linkens and Datardina (1978) used an a u t o r e g r e s s i v e m o d e l l i n g technique to determine myo-e l e c t r i c a l frequency rhythms of data c o l l e c t e d on 4 t r a c k analogue magnetic tape l i n k e d to a Data General Nova 1 6 - B i t machine with a 16-Kbit core, a back up d i s c and a T e k t r o n i c v.d.u. f a c i l i t y . T h i s method although extremely complex enables data c o l l e c t e d f o r a s h o r t p e r i o d to be ana l y s e d d e s p i t e h i g h r e s i d u a l n o i s e l e v e l s . Rumen S t a s i s A s s o c i a t e d w i t h L a c t i c A c i d o s i s I n h i b i t i o n o f gut m o t i l i t y occurs not o n l y i n the normal animal as a means o f c o n t r o l l i n g d i g e s t a passage but a l s o to a much more p r o t r a c t e d degree i n p a t h o l o g i c a l c o n d i t i o n s such as l a c t i c a c i d o s i s (West, 1977; Mullen, 1976). Rumen atony a s s o c i a t e d w i t h acute l a c t i c a c i d o s i s i n g r a i n engorged sheep and c a t t l e was a t t r i b u t e d to a number of f a c t o r s and r e -viewed by Mackenzie (1967) and Dunlop (1972). I t has been re p o r t e d t h a t as rumen l a c t i c a c i d c o n c e n t r a t i o n i n c r e a s e d and pH dropped, the amplitude and frequency o f rumen p r e s s u r e changes d i m i n i s h e d (Krogh, 1959; Broberg, 1960; Ryan, 1964; Juhasz and Szegedi, 1968). T h i s i n h i b i t o r y a c t i o n does not appear t o r e s u l t from a d i r e c t e f f e c t o f the a c i d on the rumen w a l l (Ash, 1959; Huber, 1976). I t has been shown t h a t 19 complete s t a s i s d i d not occur u n t i l two to four hours a f t e r the rumen pH was lowered to 5.0 by l a c t i c a c i d (Broberg, 1960; Juhasz and Szegedi, 1968). B a i l e and Pfander (1966) have shown t h a t i n t r a r u m i n a l i n t r o d u c t i o n of 250 ml l a c t i c a c i d (.85 M, pH 2.1) d i d not immediately a f f e c t ruminal p r e s s u r e change a c t i v i t y nor a l t e r feed i n t a k e a f t e r f i v e days o f treatment. I n t r o d u c t i o n of a c e t i c a c i d (1.0 M) how-ever caused an immediate p a r e t i c e f f e c t on m o t i l i t y . I n f u s -i o n of l a c t i c a c i d i n t o the proximal duodenum i n the sheep caused a marked i n h i b i t i o n of rumen pr e s s u r e changes i n d i -c a t i n g t h a t the s m a l l i n t e s t i n e may p l a y a major r o l e i n the g e n e r a t i o n of rumen atony i n l a c t i c a c i d o s i s (Bruce and Huber, 1973). B e l l and G r i v e l (1975) have shown t h a t HCI (60 m i l l i -e q u i v a l e n t s ) i n f u s e d i n t r a d u o d e n a l l y t o t a l l y i n h i b i t s abo-masal m y o e l e c t r i c a l a c t i v i t y . These workers suggested t h a t t h i s e f f e c t i s produced v i a duodenal chemoreceptors but do not p r e c l u d e p o s s i b l e humoral i n t e r a c t i o n s . Hunt and Knox (1969) have shown t h a t i n man, as a meal empties from the stomach to the duodenum the degree o f g a s t r i c motor i n h i -b i t i o n i s p r o p o r t i o n a l to the amount of t i t r a t a b l e a c i d i n the g a s t r i c c o n t e n t s . Mostaghni and Howard (1975) have i n v e s t i g a t e d the e f f e c t of duodenally i n f u s i n g v a r y i n g c o n c e n t r a t i o n s of HCI 20, 60 and 100 m i l l i e q u i v a l e n t s (pH 1.0, 1.4 and 1.2 r e s p e c t i v e l y ) i n sheep and found a marked i n h i b i t i o n of a n t r a l electromyographic a c t i v i t y . T o x i c compounds of ruminal o r i g i n have a l s o been im-p l i c a t e d as c a u s a t i v e f a c t o r s o f gut s t a s i s . I t has been 20 shown (Dougherty et a l . , 1975) that i n grain engorged sheep and c a t t l e , dead gram-negative bacteria release a lipopoly-saccharide endotoxin which causes a number of c i r c u l a t o r y and hematological effects and a marked i n h i b i t i o n of rumen m o t i l i t y when injected intravenously (Mullenax et a l . , 1966). When a dose of endotoxin i n excess of the estimated t o t a l endotoxin content of a l l rumen bacteria was infused i n t r a -ruminally into a normal sheep, no overt symptoms were ex-hibited. If the endotoxin does play a ro l e i n the patho-genesis of l a c t i c acidosis, other factors must also be i n -volved (Dunlop, 19 72). The involvement of histamine i n l a c t i c acidosis has been studied by many workers (Sjaastad and Stormorken, 1963; Dougherty and Ce l l o , 1947; Dain et a l . , 1955; Ahrens, 1967). The f a i l u r e to detect s i g n i f i c a n t quantities of t h i s amine i n rumen f l u i d on a time course corresponding to the i n h i -b i t i o n of rumen m o t i l i t y leaves i t s role open to question (Dunlop, 1972). Although the general decrease i n rumen pH i n grain en-gorged animals i s due to the accumulation of high concentra-tions of l a c t i c acid, the i n i t i a l drop i n pH i s reported to r e s u l t from an increase i n v o l a t i l e f a t t y acid (VFA), produc-tion (Dirksen, 1970). Solutions containing acetate, pro-pionate and butyrate infused intraruminally have been shown to i n h i b i t rumen m o t i l i t y (Ash, 1956; Ash, 1959; Shinozaki, 1958; Svendsen, 1973). Using si m i l a r techniques, Pearce (196 5) was not able to reproduce these r e s u l t s . In a review 21 o f l a c t i c a c i d p r o d u c t i o n and u t i l i z a t i o n i n the ruminant, Mackenzie (1967) s t a t e d t h a t , " I t i s probable t h a t the ab-s o r p t i o n of f r e e v o l a t i l e f a t t y a c i d w i l l c o n t r i b u t e to the rumen s t a s i s which occurs once the pH f a l l s below f i v e . " Immediate i n h i b i t i o n o f rumen m o t i l i t y was e l i c i t e d by the intravenous i n f u s i o n of the a c e t i c , p r o p i o n i c and b u t y r i c a c i d s i n doses of 10 cg/kg o f body weight (LeBars, 1954). The i n h i b i t i o n was a t t r i b u t e d to a d e p r e s s i o n of the g a s t r i c motor c e n t e r . These r e s u l t s support the f i n d i n g s t h a t a low b l o o d VFA l e v e l s t i m u l a t e s rumen or r e t i c u l u m a c t i v i t y ( B e l l , 1958). De s p i t e the complex e t i o l o g i c a l f a c t o r s noted above, Blood and Henderson (1974) s t a t e simply t h a t the n e c r o t i c damage to the rumen w a l l r e s u l t i n g from hyperosmotic i n g e s t a i s the probable cause of complete rumen s t a s i s i n l a c t i c a c i d o s i s . 22 MATERIALS AND METHODS Animals Two a d u l t ewes (#1 and #2) and a ram (#3) weighing 55, 56, and 56 kg, r e s p e c t i v e l y , were i n d i v i d u a l l y housed. The ewes were f e d 650 g of cubed a l f a l f a (90% DM, 19% p r o t e i n ) twice d a i l y w h i l s t the ram was f e d 650 g of p e l l e t e d a l f a l f a (90% DM, 15% p r o t e i n ) . S u r g i c a l Procedures Rumen e l e c t r o d e s f o r the study o f m y o e l e c t r i c a l a c t i v i t y , b a l l o o n s f o r the measurement of i n t r a r u m i n a l p r e s s u r e changes and duodenal and ruminal i n f u s i o n cannulae were implanted u s i n g the s u r g i c a l procedure d e s c r i b e d below. The d e t a i l s of the s u r g i c a l p r e p a r a t i o n s used i n t h i s study are gi v e n i n Appendix I. A n e s t h e s i a was induced by the intravenous a d m i n i s t r a -t i o n of t h i o p e n t a l sodium (Abbott) a t the r a t e of 20 mg/kg body weight, and maintained w i t h halothane (Fluothane, Ayerst) at a c o n c e n t r a t i o n o f 1.0 - 3%, i n a c l o s e d system. i ) E l e c t r o d e s The abdomen was opened through a m i d l i n e i n c i s i o n and a p a i r o f platinum needle e l e c t r o d e s (Grass E.2) 250 um i n diameter was implanted and anchored w i t h 4'0' s i l k i n the. 23 muscle l a y e r of the m i d - v e n t r a l sac (animals #1 and #2) or the mid-dorsal sac (animal #3) o f the rumen. A second p a i r of e l e c t r o d e s was implanted 5 cm d i s t a l t o the f i r s t , along the path of muscle d e p o l a r i z a t i o n as d e s c r i b e d by Ruckebusch (1970) . i i ) B a l l o o n s In order to monitor p r e s s u r e changes i n the rumen, b a l l o o n s were f i t t e d to tygon tubes, f i l l e d w i t h water and passed i n t o the v e n t r a l sac of the rumen (animals #1 and #2) v i a a 1 cm i n c i s i o n , o r i n t o the d o r s a l sac of the rumen (animal #3) v i a a rumen f i s t u l a . i i i ) Cannulae To f a c i l i t a t e i n f u s i o n s , p o l y e t h y l e n e cannulae (PE-90, Clay-Adams) were i n t r o d u c e d i n t o the duodenum to a l e n g t h of 5 cm v i a an i n c i s i o n 3 cm d i s t a l to the p y l o r u s (animals #1 and #2). The ram had been p r e v i o u s l y f i t t e d with a r e -e n t r a n t cannula a t the same l o c a t i o n i n the proximal duodenum. Po l y e t h y l e n e cannulae (PE-9 0) were a l s o i n t r o d u c e d i n t o the rumen (of animals #1 and #2), p l a c i n g the t i p immediately beneath the proximal p a i r o f e l e c t r o d e s . 24 M o n i t o r i n g of M y o e l e c t r i c a l and  Pressure Change A c t i v i t y At l e a s t f i v e days e l a p s e d f o l l o w i n g surgery before experiments were commenced. The e l e c t r o d e leads were connected to a Grass (Model 7) polygraph m u l t i c h a n n e l r e c o r d e r (1 H , z 1/2 amp Low Frequency F i l t e r : 75 H z , 1/2 amp High Frequency F i l t e r ) f o r the measurement of m y o e l e c t r i c a l a c t i v i t y . Sim-ultaneous pressure changes were recorded by connecting the tygon tubes through a Statham P25 p r e s s u r e transducer to the polygraph (0.5 to 1.0 MU/CM, 0.1Hz, 1/2 amp High Frequency F i l t e r ) . The polygraph c h a r t speed was h e l d constant a t 25 mm/min. The e l e c t r o d e and pressure leads were connected t o the r e c o r d e r 30 min p r i o r to the commencement of the i n f u s -i o n s . In order to a l l o w f o r a c c l i m a t i z a t i o n o f the animal to the experimental surroundings, data was not recorded f o r the f i r s t 10 min o f t h i s p r e i n f u s i o n p e r i o d . Determination o f D i g e s t a pH P r e l i m i n a r y experiments were conducted to a s c e r t a i n the pH of the d i g e s t a which e n t e r s the proximal duodenum. One hour a f t e r morning f e e d i n g , the r e - e n t r a n t cannula of animal #3 was dis c o n n e c t e d and 25 ml d i g e s t a samples were c o l l e c t e d from the proximal end. - The pH was then determined (pH Meter 28, Bach Simpson) and the d i g e s t a immediately r e t u r n e d t o the d i s t a l p o r t i o n of the cannula. In t o t a l , 4 2 samples were t e s t e d on three d i f f e r e n t days and Model I ANOV (Zar, 19 74) was c a r r i e d out. 25 I n f u s i o n s The e f f e c t s o f l a c t i c a c i d on ruminal m o t i l i t y were i n v e s t i g a t e d by the i n t r a d u o d e n a l , intravenous and i n t r a -ruminal i n f u s i o n s of l a c t i c a c i d a t v a r i o u s molar concentra-t i o n s and pH l e v e l s . I n f u s i o n s were conducted on each o c c a s i o n f o l l o w i n g the morning f e e d i n g and a minimum of 4 8 hr elapsed between experiments, p r e c l u d i n g the p o s s i b i l i t y o f confounding r e s i d u a l e f f e c t s . The animals were kept s t a n d i n g f o r the d u r a t i o n of the experiments i n a metal pen t h a t r e s t r i c t e d movement. A l l s o l u t i o n s were warmed to 37°C f o r the d u r a t i o n o f the i n f u s i o n t o prevent thermal e f f e c t s . i ) Intraduodenal I n f u s i o n L a c t i c a c i d s o l u t i o n s (250 ml, 0.15 M, pH 2.0, 4.0, and 6.0) made up from 85% stock s o l u t i o n (50% L(+), 50% D ( - ) , Matheson, Coleman and B e l l ) were i n f u s e d ( P o l y s t a l t i c pump, Buchler) v i a the in t r a d u o d e n a l cannula (animals #1 and #2) or through a 10 gauge hypodermic needle i n t o the r e - e n t r a n t cannula (animal #3). The a c i d was i n f u s e d a t a constant r a t e of 8 ml/min. F u r t h e r experiments were c a r r i e d out u s i n g a g r e a t e r c o n c e n t r a t i o n of l a c t i c a c i d (0.7 M) a t the same pH l e v e l s . I s o t o n i c Ringer's s a l i n e s o l u t i o n s (250 ml) were i n f u s e d i n t r a d u o d e n a l l y under i d e n t i c a l experimental c o n d i -t i o n s to pr o v i d e c o n t r o l data. 26 i i ) I n t r a r u m i n a l I n t r a r u m i n a l i n f u s i o n s c o n s i s t e d o f 1000 ml of l a c t i c a c i d (pH 2.0) a t a c o n c e n t r a t i o n o f .15 M or .7 M. The r a t e of i n f u s i o n was h e l d c o n s t a n t a t 10 ml/min. i i i ) Intravenous I n f u s i o n Intravenous i n f u s i o n s o f l a c t i c a c i d were made through cannulae (PE-90) i n t r o d u c e d i n t o the l e f t j u g u l a r v e i n two days p r i o r to experimentation. The cannulae were kept patent by the d a i l y i n f u s i o n o f an a n t i c o a g u l a n t c o n t a i n i n g 326.9 mg C i t r i c A c i d , 2.6 3 g Na C i t r a t e and 2 22 mg NaHPO^ mono b a s i c i n 100 ml E^O. S o l u t i o n s c o n t a i n i n g 20 mg/ml or 180 mg/ml Na l a c t a t e were made up from 60% stock s o l u t i o n (50% L(+), 50% D ( - ) ) and i n f u s e d v i a the j u g u l a r cannulae. The t o t a l amounts i n f u s e d v a r i e d w i t h the blood volumes of the animals. The i n -f u s i o n s were continued a t a r a t e o f 10 ml/min u n t i l the blood l a c t a t e l e v e l had been t h e o r e t i c a l l y r a i s e d by 20.0 or 280 mg%. T h i s was estimated by assuming blood volume to be 8.0% of body weight (Frandson, 1974). E q u i v a l e n t volumes o f s a l i n e were i n f u s e d to pr o v i d e c o n t r o l data. A n a l y s i s o f M y o e l e c t r i c a l and Pressure Change Data i ) Measurement The parameters of m y o e l e c t r i c a l and pre s s u r e change a c t i v i t y s t u d i e d were the s p i k e b u r s t frequency, sum o f spike 27 b u r s t d u r a t i o n , sum o f spi k e b u r s t magnitude, pressure change (peaks) frequency, sum o f pre s s u r e change d u r a t i o n and sum of pres s u r e change magnitude. Spike bursts were recorded for those values exceeding 25 mV d e f l e c t i o n . Pressure changes were recorded f o r those v a l u e s exceeding 2.5 mm Hg. Pressure changes t h a t r e s u l t e d d i r e c t l y from animal movement were not i n c l u d e d i n the a n a l y s i s . Breathing a r t i f a c t s and s k e l e t a l muscle a c t i v i t y were e s s e n t i a l l y e l i m i n a t e d from the r e c o r d i n g s by the High and Low Frequency F i l t e r s on the Grass r e c o r d e r . The data was then analysed and p l o t t e d by the U n i v e r s i t y o f B r i t i s h Columbia AMDAHL 470 computer u s i n g the U n i v e r s i t y of C a l i f o r n i a B i o -medical Program 'P6D'. i i ) A n a l y s i s A l l p o s s i b l e c o r r e l a t i o n s (negative and p o s i t i v e ) among the parameters were c a l c u l a t e d on the pooled data o f a l l e x p e r i -ments. T h i s enabled the s e l e c t i o n o f one of the m y o e l e c t r i c a l parameters f o r use as a r e l i a b l e index of rumen m o t i l i t y . i i i ) P l o t s The d u r a t i o n o f m y o e l e c t r i c a l s p i k e b u r s t ERA was p l o t t e d by computer f o r each experiment as f o l l o w s . The means of s p i k e b u r s t d u r a t i o n from two c o n s e c u t i v e one minute i n t e r -v a l s were determined f o r the whole o f each experiment. Thus f o r an experiment 120 min i n le n g t h , s i x t y 2 minute mean values were c a l c u l a t e d . These values were then p l o t t e d as a percentage of the mean of the p r e i n f u s i o n p e r i o d a g a i n s t time. 2.8. RESULTS pH o f Duodenal D i g e s t a The pH v a l u e s o f the proximal duodenal d i g e s t a o b t a i n e d from the r e - e n t r a n t cannulae of animal #3 are shown i n Table 1. I t can be noted t h a t a marked v a r i a t i o n i n pH o c c u r r e d d u r i n g each sampling p e r i o d . Not o n l y was a range of values found w i t h i n each sampling p e r i o d but s i g n i f i c a n t v a r i a t i o n between days was a l s o noted. The pH of the d i g e s t a e n t e r i n g the i n t e s t i n e ranged from a low o f pH 2.00 (day A) to a high o f 2.95 (day C ) . T h i s d i f f e r e n c e i s e q u i v a l e n t to n e a r l y a 1 0 - f o l d v a r i a t i o n i n H+ c o n c e n t r a t i o n . Using s i n g l e f a c t o r a n a l y s i s o f v a r i a n c e (Zar, 1974) the pH values were shown to be s i g n i f i c a n t l y d i f f e r e n t between days (P <0.05). Phy s i o l o g i c a1 Record s An example o f rumen pr e s s u r e and m y o e l e c t r i c a l r e c o r d -ings o b t a i n e d s i m u l t a n e o u s l y d u r i n g the course of an e x p e r i -ment i s presented i n F i g u r e 1. The top t r a c i n g shows rumen pr e s s u r e changes and the bottom t r a c i n g e x e m p l i f i e s s p i k e b u r s t e l e c t r i c a l response a c t i v i t y . The c l o s e a s s o c i a t i o n between the p r e s s u r e changes and s p i k e b u r s t s i s e v i d e n t . Some of the p r e s s u r e changes do not c o r r e l a t e w i t h a pro-nounced b u r s t o f m y o e l e c t r i c a l a c t i v i t y (arrow). These Table 1. pH of c o n s e c u t i v e duodenal d i g e s t a samples c o l l e c t e d from r e - e n t r a n t cannula 1 h a f t e r f e e d i n g on 3 d i f f e r e n t days. pH of duodenal digesta D a y l 3 2.50 2.50 2.45 2.15 2.30 2.15 2.00 2.00 2.05 2.00 2.05 2.05 2.05 2.00 Day II 5 3 2.40 2.40 2.40 2.30 2.35 2.25 2.25 2.30 2.30 2.40 2.30 2.30 2.40 2.20 Day I I I C 2.60 2.55 2.55 2.60 2.50 2.60 2.55 2.80 2.95 2.50 2.70 2.50 2.60 2.70 Numbered days w i t h s u p e r s c r i p t s (a,b,c) are s i g n i f i c a n t l y d i f f e r e n t (P<0.05). t o F i g u r e 1. Simultaneously recorded rumen pressure changes and m y o e l e c t r i c a l a c t i v i t y , (Arrow i n d i c a t e s p r e s s u r e change independent of spike b u r s t a c t i v i t y ) . CO o 31 peaks g e n e r a l l y r e s u l t from t r a n s m i s s i o n o f p r e s s u r e changes o c c u r r i n g i n o t h e r organs such as the r e t i c u l u m or omasum. C o r r e l a t i o n Among Rumen M o t i l i t y Parameters The parameters of s p i k e b u r s t d u r a t i o n , frequency and magnitude were o b t a i n e d f o r a t o t a l of 4477 minutes i n 44 experiments. Pressure change frequency, d u r a t i o n and magni-tude val u e s were p a i r e d w i t h o n l y 2075 o f these one minute o b s e r v a t i o n s . A l l p o s s i b l e c o r r e l a t i o n s between these values are presented i n the c o r r e l a t i o n m a t r i x i n Table 2. Among the parameters t e s t e d , the m y o e l e c t r i c a l ones e x h i b i t e d the h i g h e s t c o r r e l a t i o n s and were h i g h l y s i g n i f i c a n t (P <.05). I n f u s i o n Experiments  Intraduodenal A d m i n i s t r a t i o n of L a c t i c A c i d i ) pH 2.0 In a s e r i e s o f 17 experiments i n which l a c t i c a c i d (pH 2.0) was i n f u s e d i n t r a d u o d e n a l l y , a marked r e d u c t i o n i n rumen m o t i l i t y was noted i n each case. A r e c o r d i n g of simultane-o u s l y obtained rumen p r e s s u r e and m y o e l e c t r i c a l a c t i v i t y at the commencement o f a 250 ml l a c t i c a c i d (0.15 M) i n f u s i o n i s shown i n F i g u r e 2. T o t a l i n h i b i t i o n o f a c t i v i t y o c c u r r e d 1.5 min a f t e r the commencement o f the i n f u s i o n . A t t h i s p o i n t 12.0 ml o f a c i d would have been i n f u s e d . I n f u s a t e F i g u r e 2. E f f e c t of duodenal i n f u s i o n of 0.15 M l a c t i c a c i d (pH 2.0) on simultaneously recorded rumen pressure changes and m y o e l e c t r i c a l a c t i v i t y . 33 e f f e c t s on spike b u r s t d u r a t i o n are shown i n F i g u r e 3. A p r e c i p i t o u s drop i n a c t i v i t y c u l m i n a t i n g i n t o t a l i n h i b i t i o n i s c l e a r l y demonstrated. R e s u l t s o f each experiment conduc-ted i n t h i s study are g i v e n i n Appendix II. In the ten experiments conducted w i t h .15 M l a c t i c a c i d , two showed t o t a l i n h i b i t i o n o f a c t i v i t y ( 0 % of the p r e i n f u s i o n mean) immediately f o l l o w i n g i n f u s i o n commencement. The other 8 experiments e x h i b i t e d i n i t i a l i n h i b i t o r y phases r a n g i n g i n magnitude from the 5 to 30% l e v e l o f the p r e i n f u s i o n mean. Th i s i n i t i a l i n h i b i t o r y phase l a s t e d f o r o n l y a s h o r t p e r i o d of time. In each experiment, a marked re c o v e r y of rumen m o t i l i t y had o c c u r r e d by the f i f t e e n t h minute o f i n f u s i o n . T h i s r e c o v e r y phase ranged i n magnitude from a low o f 50% o f the p r e i n f u s i o n mean (Expt. 3) to a h i g h of 115% (Expt. 5). The l e n g t h of the recovery phase v a r i e d anywhere from 6 t o 16.5 min (Expts. 5 and 9, r e s p e c t i v e l y ) . Rather than s i g n a l l i n g a r e t u r n to the p r e i n f u s i o n a c t i v i t y p a t t e r n , the r e c o v e r y phase was f o l l o w e d by f u r t h e r s u c c e s s i v e i n h i b i t o r y and r e c o v e r y phases. These p e r i o d s o f s p o r a d i c r e c o v e r y and d e p r e s s i o n o f m o t i l i t y which e x h i b i t e d marked v a r i a b i l i t y i n magnitude and d u r a t i o n o c c u r r e d up to 30 - 40 min a f t e r i n f u s i o n t e r m i n a t i o n . A r a p i d r e c o v e r y o f rumen m o t i l i t y to p r e i n f u s i o n l e v e l s f o l l o w e d these p e r i o d s of f l u c t u a t i n g a c t i v i t y . Although the i n i t i a l i n h i b i t o r y and r e c o v e r y phases o c c u r r e d on approximately the same time course i n a l l experiments, the subsequent phases e x h i b i t e d Table 2. C o r r e l a t i o n s among rumen m y o e l e c t r i c a l parameters. M y o e l e c t r i c a l Pressure Change Du r a t i o n Frequency . Magnitude Duration Frequency Magnitude M y o e l e c t r i c a l D u r a t i o n Frequency Magnitude 1.00 0.72 0.72 1.00 0.78 1.00 Pressure D u r a t i o n Frequency Magnitude 0.45 0.53 0.47 0.56 0.65 0.63 0.45 0.55 0.48 1. 00 0.70 1.00 0.66 0.74 1.00 A l l the above c o r r e l a t i o n s are s t a t i s t i c a l l y s i g n i f i c a n t (P< 0.05) 200 175 150 125 100 75 50 25 0 1 -15 15 30 45 Time (min) 60 75 90 105 120 Experiment 1, E f f e c t o f i n t r a d u o d e n a l i n f u s i o n o f 0.15 M l a c t i c a c i d (pH 2.0) on rumen s p i k e b u r s t d u r a t i o n (animal #1). Figure 3. 36 no temporal s i m i l a r i t i e s . The remaining seven experiments i n t h i s pH series u t i l i z e d a more concentrated 0.7 M l a c t i c acid infusate. Effects similar to those r e s u l t i n g from 0.15 M acid infusion occurred immediately upon infusion of the 0.7 M solutions. Five of the seven experiments showed t o t a l i n h i b i t i o n of a c t i v i t y by the tenth minute of infusion whereas the other two exhibited a decline to 20% and 35% (Expts. 13 and 15, respectively) of the preinfusion l e v e l . As occurred with the 0.15 M experiments, the i n i t i a l i n h i b i t o r y phase lasted only a short time. There then occurred a marked recovery of rumen m o t i l i t y ranging i n magnitude from a low of 20% (Expt. 12) to a high of 105% (Expt. 15) of the preinfusion mean. This i n i t i a l recovery phase was followed by an extended period of m o t i l i t y fluctuations of varying duration and magnitude as occurred with the 0.15 M infusate. These periods lasted from up to 35 (Expt. 15) to 105 (Expt. 12) min af t e r infusion termination culminating i n a rapid recovery to preinfusion l e v e l s . i i ) pH 4.0 Pronounced changes i n the rhythmic rumen m o t i l i t y were noted i n a series of experiments i n which l a c t i c acid at pH 4.0 was infused intraduodenally. The m o t i l i t y patterns gen-erated by infusion of 0.15 M l a c t i c acid were markedly d i s -similar between the experiments. These ef f e c t s are shown in Figures 4 and 5. Experiment 18 exhibits a rapid decrease Figure 4. 200 * 150 c o •H 4J u TJ +J W )-l A CO 175 125 100 75 50 25 -15 15 30 45 60 Time (min) 75 90 10'5 120 Experiment 19. E f f e c t of intraduodenal infusion of 0.15 M l a c t i c acid (pH 4.0) on rumen spike burst duration (animal #1). CO CO Figure 5. 39 i n m o t i l i t y immediately f o l l o w i n g infusion,, a re c o v e r y phase fo l l o w e d by numerous p e r i o d s of i n h i b i t i o n and recovery. F u l l r e c o v e r y t o p r e i n f u s i o n l e v e l s o c c u r r e d some 30 min a f t e r i n f u s i o n t e r m i n a t i o n . Experiment 19, however, d i d not e x h i -b i t s i m i l a r p h a s i c trends i n m o t i l i t y t h a t w i t h any c e r t a i n t y c o u l d be a t t r i b u t e d t o the i n f u s i o n . I n t r a d u o d e n a l l y i n f u s e d 0.7 M pH 4.0 l a c t i c a c i d e x h i -b i t e d e q u a l l y v a r i e d e f f e c t s on spi k e b u r s t a c t i v i t y , as shown i n F i g u r e s 6 and 7. I t can be seen i n Experiment 20 t h a t i n i t i a -t i o n of i n f u s i o n caused a r a p i d i n h i b i t i o n of a c t i v i t y t o the 20% l e v e l o f the p r e i n f u s i o n mean. T h i s p e r i o d was fo l l o w e d by a marked recover y phase. Experiment 21 a l s o e x h i b i t e d an i n i t i a l i n h i b i t o r y phase, although not as severe, as w e l l as a p e r i o d o f recovery of m y o e l e c t r i c a l a c t i v i t y . M o t i l i t y p a t t e r n s f o l l o w i n g the i n i t i a l r e c o v e r y phase i n Experiment 21 e x h i b i t a g e n e r a l i z e d d e p r e s s i o n as c h a r a c t e r i z e d by sp o r a d i c p e r i o d s of a c t i v i t y recovery and i n h i b i t i o n . The data o b t a i n e d i n Experiment 2 0 show a much more p r o t r a c t e d i n h i b i t i o n o f m y o e l e c t r i c a l a c t i v i t y f o l l o w i n g the i n i t i a l r e c o v e r y phase. F u l l r e c o v e r y of p r e i n f u s i o n a c t i v i t y o c c u r r e d some 60 min a f t e r i n f u s i o n t e r m i n a t i o n . i i i ) pH 6.0 The e f f e c t on rumen m o t i l i t y o f i n t r a d u o d e n a l l y i n f u s -i n g 250 ml of 0.15 M l a c t i c a c i d a t pH 6.0 was widely d i -vergent from t h a t found i n experiments i n v o l v i n g 0.7 M a c i d . 200 175 150 c o ? 1 2 5 M -P X! •H Ui 100 75 50 25 0 L -15 15 30 45 60 Time (min) 75 90 105 120 Experiment 20. E f f e c t of intraduodenal infusion of 0.7 M l a c t i c acid (pK 4.0) on rumen spike burst duration (animal #1). Figure 6. C O • iH 4-> (0 SH TJ. -P Ui U 73 .Q 0) 200 175 150 125 100 75 Cu w 50 25 OL i 90 -15 15 30 45 60 Time (min) 75 105 120 Experiment 21. E f f e c t of intraduodenal i n f u s i o n of 0.7 M l a c t i c a c i d (pH 4.0) on rumen spike b u r s t d u r a t i o n (animal #3). Figure 7. 42 The r e s u l t s from the 0.15 M experiments d i d not show any f l u c t u a t i o n s i n m o t i l i t y t h a t are d i s c e r n a b l y d i f f e r e n t from those o c c u r r i n g i n the p r e i n f u s i o n p e r i o d s . In the e x p e r i -ments i n v o l v i n g the more co n c e n t r a t e d i n f u s a t e , the gen e r a l changes i n the m o t i l i t y p a t t e r n seen a t the pre v i o u s pH l e v e l s (2.0 and 4.0) were apparent. A p r e c i p i t o u s decrease i n s p i k e b u r s t d u r a t i o n to 45 and 0% ( t o t a l i n h i b i t i o n ) i n Experiments 24 and 25, r e s p e c t i v e l y , was f o l l o w e d by a s h o r t recovery phase. A p e r i o d o f sp o r a d i c f l u c t u a t i o n i n m o t i l i t y then ensured, l a s t i n g 20 to 60 min a f t e r i n f u s i o n termina-t i o n . An abrupt recovery o f m o t i l i t y marked the end o f t h i s o s c i l l a t o r y a c t i v i t y r e a c h i n g a peak of 145 and 200% and then d e c l i n e d , approaching the p r e i n f u s i o n l e v e l s . i v ) Intraduodenal S a l i n e Experiments 26 through 31 were c a r r i e d out t o study the e f f e c t s on rumen m o t i l i t y of i n t r a d u o d e n a l i n f u s i o n o f 250 ml of p h y s i o l o g i c a l s a l i n e . I t can be seen i n F i g u r e 8 t h a t the v a r i a b i l i t y i n sp i k e b u r s t d u r a t i o n immediately f o l l o w i n g i n f u s i o n was s i m i l a r to t h a t found i n the p r e i n f u s i o n p e r i o d . In c o n t r a s t to l a c t i c a c i d i n f u s i o n , there were no p r e c i p i -tous drops i n m o t i l i t y immediately f o l l o w i n g i n f u s i o n , nor were there any p e r i o d s of p r o t r a c t e d i n h i b i t i o n i n the e x p e r i -ments i n t h i s s e r i e s . The g r e a t e s t range i n p r e i n f u s i o n m o t i l i t y , r anging from a low of 75% to a high of 145% of the p r e i n f u s i o n mean occur r e d i n Experiment 26. The g r e a t e s t w X TJ CD N H-3 (D 3 rt Spike b u r s t d u r a t i o n (%) to • o td 3 Hi H> H ro o 3 rt ro 3 0 H» CO TJ H- — i H- 3 cn X r t ro n •-3 tr a **. c c 3 K 0 CD iQ C rt ro co H 3 3 o ro Qi $» H-C i—• 3 00 n • 0> p. rt 3 H- i-h 0 C 3 co — O (D 3 3 H" O 3 Hi 0) o 3* U) CO ' - ' H* • O H" O - j H-O £U M CO 0) VD 1—1 o H-3 (0 o ~1— to cn o cn O O to Cn cn o cn to o o 44 v a r i a b i l i t y i n m o t i l i t y immediately following infusion, rang-ing from a low of 60 to a high of 175% of the preinfusion mean occurred i n Experiment 27. Intraruminal Administration 0 f Lactic Acid (pH 2.0) The e f f e c t of. intraruminal infusion of 1000 ml of l a c t i c acid (pH 2.0) on spike burst duration i s shown i n Figure 9. It can be seen that the v a r i a b i l i t y i n spike burst duration following the commencement of infusion was similar to that found i n the preinfusion periods. There were no p r e c i p i -tous drops i n m o t i l i t y immediately following infusion, nor did any periods of protracted i n h i b i t i o n occur during the course of the experiments. Experiments i n t h i s series were conducted using either 0.15 M (32 and 33) or 0.7 M (34) l a c t i c acid infusions. No apparent differences i n m o t i l i t y were observed between the two infusate concentrations. Intravenous Administration of Lactic Acid i) Sodium Lactate 20 mg/ml Four experiments were conducted i n which 20 mg/ml of Na lactate was infused intravenously. It can be seen from Figure 10 that the v a r i a b i l i t y i n myoelectrical a c t i v i t y following the commencement of infusion was similar to that seen i n the preinfusion period. The only exception to t h i s finding occurred i n Experiment 35 i n which a precipitous 200 175 L Time (min) Experiment 34. E f f e c t of i n t r a r u m i n a l i n f u s i o n of 0.7 M l a c t i c a c i (pH 2.0) on rumen spike burst d u r a t i o n (animal #3). Figure 9. 200 1 7 5 h ~ 1 5 0 ~ Time (min) Experiment 38. E f f e c t of intravenous i n f u s i o n of sodium l a c t a t e (20 mg/ml) on rumen spike burst d u r a t i o n (animal #3). Figure 10. 47 drop i n spi k e b u r s t d u r a t i o n from 150 to 80% o c c u r r e d a t minute 3 of the i n f u s i o n . However, t h i s r e d u c t i o n was not as great i n magnitude as the i n h i b i t i o n t h a t o c c u r r e d a t min -10 of the p r e i n f u s i o n p e r i o d i n the same experiment. There was no p r e c i p i t o u s drops i n spike b u r s t d u r a t i o n o f s i m i l a r mag-ni t u d e i n e i t h e r the pre- or p o s t - i n f u s i o n p e r i o d s i n the oth e r experiments. i i ) Sodium L a c t a t e 180 mg/ml Four experiments were conducted i n t h i s s e r i e s i n which 180 mg/ml was i n f u s e d i n t r a v e n o u s l y . I t can be seen from F i g u r e 11 t h a t the v a r i a b i l i t y i n a c t i v i t y was very s i m i l a r immediately f o l l o w i n g i n f u s i o n commencement t o t h a t i n the p r e i n f u s i o n p e r i o d . A l s o t h e r e was l i t t l e d i f f e r e n c e between these data and those obtained a t the lower i n f u s a t e concen-t r a t i o n . A' marked i n h i b i t i o n o c c u r r e d i n the p r e i n f u s i o n a c t i v i t y o f Experiment 39 dropping from 120% to 60%. A s i m i l a r i n h i -b i t i o n o c c u r r e d a t minute 8 o f the i n f u s i o n i n which a c t i v i t y dropped from 12 0% o f the p r e i n f u s i o n mean t o 50%. There were no p e r i o d s o f p r o t r a c t e d i n h i b i t i o n i n any of the experiments. i i i ) S a l i n e Two p h y s i o l o g i c a l s a l i n e intravenous c o n t r o l experiments were conducted. V a r i a b i l i t y i n spike b u r s t d u r a t i o n f o l l o w i n g time 0 was s i m i l a r to t h a t found i n the p r e i n f u s i o n p e r i o d . 200 F i g u r e 11. 49 The experiments do not show p r e c i p i t o u s drops i n m o t i l i t y immediately a f t e r i n f u s i o n commencement nor were p e r i o d s o f p r o t r a c t e d i n h i b i t i o n induced up to 1 hr a f t e r i n f u s i o n commencement. 50 DISCUSSION pH of Duodenal D i g e s t a P r e l i m i n a r y experiments were conducted i n which the pH of the duodenal contents o b t a i n e d from the r e - e n t r a n t can-nula (animal #3) was measured i n order t o e s t a b l i s h the pH of the a c i d to be i n f u s e d i n these s t u d i e s . The r e s u l t s (Table 1) f i t the range of pH 2.0 -'3.0 determined by o t h e r workers i n sheep f e d s i m i l a r r a t i o n s (Ash, 1961; Masson, 1952). C o n s i d e r a t i o n was a l s o given to the f a c t t h a t rumen, r e t i -culum and omasal pH drops to l e v e l s below 4.0 i n c o n d i t i o n s of severe l a c t i c a c i d o s i s (Bond, 19 55). The h i g h l y a c i d i c environment of the abomasum would f u r t h e r decrease the pH of the d i g e s t a , thus chyme e n t e r i n g the duodenum i n animals s u f f e r i n g from l a c t i c a c i d o s i s would l i k e l y f i t the lower end of t h i s pH range. T h e r e f o r e , l a c t i c a c i d s o l u t i o n s were i n t r o d u c e d i n t r a d u o d e n a l l y at pH 2.0 to approximate the a c i d i c environment p r e v a l e n t i n l a c t i c a c i d o s i s . S o l u t i o n s of h i g h e r pH (4.0 and 6.0) were a l s o i n f u s e d t o determine i f the degree of l a c t i c a c i d d i s s o c i a t i o n (pk = 3.9) a f f e c t e d the a c i d - i n d u c e d m o t i l i t y changes. Bruce and Huber (1973) i n v e s t i g a t e d the e f f e c t of duodenal i n f u s i o n o f 0.7 M l a c t i c a c i d on ruminal p r e s s u r e change a c t i v i t y . I t was f e l t however, t h a t t h i s concentra-t i o n of a c i d might e x e r t confounding osmotic e f f e c t s on m o t i l i t y . In order to minimize t h i s f a c t o r , i n f u s i o n s 51 were c a r r i e d out u t i l i z i n g 0.15 M l a c t i c a c i d s o l u t i o n s . The h i g h e r c o n c e n t r a t i o n s o l u t i o n s (0.7 M) were i n f u s e d to p r o v i d e comparative data. I n f u s i o n r a t e s of 10 ml/min i n c a l v e s ( B e l l and G r i v e l , 1975), 25 ml/min i n man (Roze, 1975) and 8 ml/min (Bruce and Huber, 19 73) have been used f o r the i n t r a d u o d e n a l i n t r o d u c -t i o n of v a r i o u s a c i d s . The r a t e of 8 ml/min was used i n t h i s study as i t c l o s e l y approximated the mean net a b o r a l flow from the duodenum of sheep as determined by S i n g l e t o n (1961). P h y s i o l o g i c a l Recordings The m y o e l e c t r i c a l and p r e s s u r e change data ( i . e . , F i g u r e 1) o b t a i n e d i n t h i s study are s i m i l a r to e s t a b l i s h e d v a l u e s . The rhythmic a c t i v i t y of the rumen d o r s a l sac i n sheep has been shown to be approximately 2 pressure r e l a t e d s p i k e bursts/min (Ruckebusch, 1970). Reid (1963) has found p r e s s u r e changes i n sheep f o l l o w i n g f e e d i n g to i n c r e a s e from l e s s than 2 to approximately 3/min. A value o f 2.5 p r e s s u r e r e l a t e d s p i k e bursts/min was found to be the mean o f a l l the p r e i n -f u s i o n data ( c o n t r o l period) i n t h i s study. Ruckebusch (1970) found t h a t the d u r a t i o n o f the p r e s s u r e changes d i d not exceed 6 sec and the time course of the s p i k e b u r s t s to be 2-3 seconds. In t h i s study, the means of p r e i n f u s i o n p r e s s u r e change d u r a t i o n and spike b u r s t d u r a t i o n were approximately 13 and 5 seconds, r e s p e c t i v e l y . Comparisons between t h i s and other s t u d i e s however, should be undertaken 52 with g r e a t c a u t i o n . The r e c o r d i n g apparatus used i n t h i s work u t i l i z e d components much d i f f e r e n t from those i n pre-v i o u s s t u d i e s and thus the s e n s i t i v i t y of the systems would be incongruent. C o r r e l a t i o n s Among Rumen M o t i l i t y Parameters Oigaard and Dorph (1974a) c a l c u l a t e d a l l p o s s i b l e c o r -r e l a t i o n s among the human small i n t e s t i n e m o t i l i t y para-meters o f spike b u r s t and pressure change d u r a t i o n and mag-ni t u d e . These c a l c u l a t i o n s were based on one thousand pr e s s u r e r e l a t e d s p i k e b u r s t s . The c a l c u l a t i o n s d i d not i n c l u d e frequency v a l u e s . I t was found t h a t the lowest c o r r e l a t i o n s were those a s s o c i a t e d w i t h s p i k e b u r s t amplitude whereas the h i g h e s t were found between pr e s s u r e d u r a t i o n and amplitude. The h i g h e s t m y o e l e c t r i c a l c o r r e l a t e s were those a s s o c i a t e d w i t h s p i k e b u r s t d u r a t i o n . These workers a l s o found a c l o s e a s s o c i a t i o n between sp i k e b u r s t d u r a t i o n and bowel m o t i l i t y as seen by c i n e f l u o r o g r a p h i c techniques. The number of one minute o b s e r v a t i o n s (4477) used i n t h i s study to e s t a b l i s h the c o r r e l a t i o n s among m y o e l e c t r i c and p r e s s u r e change parameters r e p r e s e n t s one of the l a r g e s t numbers used i n s t u d i e s o f t h i s k i n d . The c o r r e l a t i o n s obtained i n t h i s study were found to be h i g h e s t w i t h i n myo-e l e c t r i c a l and w i t h i n the p r e s s u r e change parameters. The a s s o c i a t i o n between m y o e l e c t r i c a l and pressure parameters were somewhat lower although h i g h l y s t a t i s t i c a l l y s i g n i f i c a n t 53 (P < 0.05). Based on the mathematical rela t i o n s h i p between magnitude (amplitude) and frequency of waveforms discussed by Greenberg (1975), one would expect within pressure change parameter correlations to be higher than correlations between pressure change and myoelectrical data. The s t a t i s t i c a l l y i n s i g n i f i c a n t correlations between spike burst amplitude and the pressure change parameters found by the Danish workers were found to be highly s i g n i f i c a n t i n t h i s study. In general, the correlations obtained were higher than those reported by Oigaard and Dorph (1974a). This may be attributed to the greater number of observations i n t h i s study (four times as many), procedural differences, species v a r i a t i o n or organ v a r i a t i o n . Rumen pressure change values are generally more r e l i a b l e than data obtained from the i n t e s t i n e primarily because the intraluminal recording apparatus tends to gener-ate mechanical a r t i f a c t s i n the narrow duodenum. The high degree of c o r r e l a t i o n among the d i f f e r e n t parameters i n t h i s study iridicates that rumen myoelectrical a c t i v i t y i s a r e l i a b l e indicator of rumen m o t i l i t y . Choice of Parameters1 for P l o t t i n g the Data In many experiments following the intraduodenal infusion of l a c t i c acid at pH 2.0 i t was noted that the f i r s t i n d i c a -t i o n of i n h i b i t i o n of m o t i l i t y was a reduction i n the dura-ti o n of spike bursts, followed by depression i n the other parameters. Thus i t was concluded that the most sensitive 54 i n d i c a t o r o f m o t i l i t y was spike b u r s t d u r a t i o n and t h i s para-meter was chosen f o r the g r a p h i c r e p r e s e n t a t i o n o f the data. The q u i c k e r response of rumen s p i k e b u r s t d u r a t i o n t o duo-denal a c i d i f i c a t i o n may account f o r the c o r r e l a t i o n c o e f f i c i e n t i n t h i s parameter being l e s s than one. The low frequency o f the spike b u r s t s and r e s u l t a n t pressure changes made i n t e r p r e t a t i o n o f graphs i n which each p o i n t was p l o t t e d extremely d i f f i c u l t . S u b t l e v a r i a t i o n s i n m o t i l i t y u n r e l a t e d to the i n t r a d u o d e n a l i n t r o d u c t i o n o f a c i d tended to mask the a c i d generated changes. T h e r e f o r e f o r the e n t i r e t y o f each experiment, s p i k e b u r s t d u r a t i o n o f two con-s e c u t i v e one minute p e r i o d s was summed and the mean determined f o r computer p l o t t i n g . D e s p i t e r i g o r o u s attempts t o s t a n d a r d i z e f e e d i n g pat-t e r n s , experimental procedures, housing c o n d i t i o n s and e f f o r t s to minimize pre-experimental excitement, a g r e a t d e a l of v a r -i a b i l i t y i n the p r e i n f u s i o n parameter means was observed between the experiments. For example, the p r e i n f u s i o n mean of s p i k e b u r s t d u r a t i o n i n Experiment 1 was 21.2 seconds of a c t i v i t y / m i n , which was more than t h r e e times the p r e i n f u s i o n mean of 6.0 sec of a c t i v i t y / m i n i n Experiment 13. P a r t of t h i s v a r i a b i l i t y may be a t t r i b u t e d to day to day f l u c t u a t i o n s i n the pH o f the d i g e s t a e n t e r i n g the duodenum as shown i n Table 1. A l s o , i t has been r e p o r t e d t h a t over a p e r i o d o f time ( i . e . , 2-3 weeks) the s e n s i t i v i t y of the implanted e l e c t r o d e s d i m i n i s h e d (Ruckebusch, 1970). T h i s phenomenon which o c c u r r e d i n a l l the p r e p a r a t i o n s i n t h i s study was 55 a t t r i b u t e d t o encasement of the e l e c t r o d e s i n f i b r i n . P ost-mortem examination of the i m p l a n t a t i o n s i t e confirmed t h i s o b s e r v a t i o n by Ruckebusch (1970). Thus, the comparison of l a c t i c a c i d induced changes between experiments i n a b s o l u t e terms would be of q u e s t i o n a b l e m e r i t . The c o n v e r s i o n o f a l l the mean spike b u r s t d u r a t i o n v a l u e s t o a percentage o f the p r e i n f u s i o n mean o f each experiment engendered a standard of u n i f o r m i t y t h a t made comparisons between experiments meaning-f u l . The d i f f e r e n t time course o f the i n h i b i t o r y and r e -covery phases between experiments rendered s t a t i s t i c a l t r e a t -ment of experimental s e r i e s i m p r a c t i c a l as d i s c u s s e d by Mostaghni and Howard (1974). Intraduodenal A d m i n i s t r a t i o n of L a c t i c A c i d Mode of I n h i b i t o r y A c t i o n o f Duodenal A c i d i f i c a t i o n The i n h i b i t i o n i n rumen m o t i l i t y seen a f t e r i n t r a d u o -denal i n f u s i o n of l a c t i c a c i d a t pH 2.0 may have been caused by one or more mechanisms. The r a p i d i t y o f onset however, suggests t h a t n e u r a l pathways may pl a y a prime r o l e i n t h i s response. Andrews and Andrews (1971) found t h a t upon i n t r o -d u c t i o n o f h y d r o c h l o r i c a c i d s o l u t i o n s i n t o r a b b i t duodenum, near instantaneous, i n t e n s e v o l l e y s of a c t i o n p o t e n t i a l s o c c u r r e d i n the a f f e r e n t nerves o f the duodenal w a l l . Res-ponses r e a c h i n g a maximum t h i r t y seconds a f t e r i n f u s i o n 56 commencement and l a s t i n g up to three minutes were noted. S i m i l a r l y , the i n i t i a l i n h i b i t o r y responses to l a c t i c a c i d a t pH 2.0 seen i n Experiments 1 - 1 7 o c c u r r e d very r a p i d l y , the p e r i o d o f maximum i n h i b i t i o n seldom l a s t i n g f o r more than f o u r minutes. Cooke (1974) i n v e s t i g a t e d emptying o f a s a l i n e meal i n days a f t e r i n t r a d u o d e n a l i n f u s i o n of v a r i o u s h y d r o c h l o r i c a c i d s o l u t i o n s . I t was found t h a t a r a p i d i n h i b i t i o n o f emptying o c c u r r e d w i t h i n 1 min of i n f u s i o n commencement. These experiments i n d i c a t e d t h a t a c i d r e c e p t o r s were present i n the proximal duodenum ( f i r s t 5 cm) and the r a p i d i t y of the onset of i n h i b i t i o n was c o n s i s t e n t with a nervous r e f l e x (Cooke and C l a r k e , 1976). I t has been shown by Schapiro and Woodward (1959) t h a t combined vagotomy and complete b i l a t e r a l thoracolumbar sympathectomy d i d not a f f e c t the a c i d induced e n t e r o g a s t r i c r e f l e x . However, c e l i a c ganglionectomy com-p l e t e l y a b o l i s h e d t h i s i n h i b i t o r y mechanism i n d i c a t i n g t h a t the pathway i s through the p o s t - g a n g l i o n i c sympathetics. Con-t r a r y to these f i n d i n g s Svendsen (1973) s t a t e s t h a t , "The m o t i l i t y of the ruminant stomach i s c o o r d i n a t e d , by r e f l e x e s from the parasympathetic nervous system." T h i s a s s e r t i o n was supported by the work of T i t c h e n (1958 and 1960) who showed t h a t e l e c t r i c a l s t i m u l a t i o n o f the vagus i n d e c e r e b r a t e p r e -p a r a t i o n s o f sheep, goat and c a l v e s evoked ruminal c o n t r a c -t i o n s . T h i s e f f e c t was a b o l i s h e d by a d m i n i s t r a t i o n of a t r o -p i n e . Adding f u r t h e r weight to t h i s argument are the f i n d i n g s 57 of Duncan (1953) which show th a t vagotomy a b o l i s h e s the normal rhythmic a c t i v i t y of t h e r e t i c u l u m and rumen i n sheep. The gut hormonal a x i s and i t s involvement i n the e n t e r o -g a s t r i c r e f l e x have been questioned. I t i s g e n e r a l l y accepted t h a t duodenal a c i d i f i c a t i o n induces s e c r e t i n r e l e a s e . How-ever, the amount of a c i d e n t e r i n g the f i r s t p a r t of the duodenum r e q u i r e d to i n h i b i t g a s t r i c emptying i s such t h a t the q u a n t i t y of s e c r e t i n r e l e a s e d would be u n l i k e l y to have any e f f e c t on the g a s t r i c musculature (Cooke and C l a r k e , 1976; Ward and Bloom, 1974). Moreover, experiments i n which s e c r e t i n has been shown to decrease g a s t r i c emptying have used doses which are probably u n p h y s i o l o g i c a l (Chvasta and Cooke, 1973). Kowolewski and Kolodej (1977) have shown t h a t i n f u s i o n of s e c r e t i n (60 U/hr) i n h i b i t s ERA and mechanical a c t i v i t y (as d etected by s t r a i n gauges) i n the g a s t r i c antrum of canine stomach p r e p a r a t i o n s . The l e v e l s of hormone i n c o n j u n c t i o n with the v a g a l s t i m u l a t i o n which induced these e f f e c t s were ph a r m a c o l o g i c a l . They suggested t h a t the i n -h i b i t o r y a c t i o n o f the hormone on g a s t r i c motor a c t i v i t y "may not be o c c u r r i n g under p h y s i o l o g i c a l c o n d i t i o n s " . I t has been suggested by K e l l y e t a l . (1969) t h a t s e c r e t i n may a c t " p o s s i b l y i n d i r e c t l y through c o n t r o l l i n g mechanisms". Bruce and Huber (1973) i n v e s t i g a t e d the e f f e c t of i n t r a -duodenal l a c t i c a c i d i n f u s i o n and i ntravenous s e c r e t i n i n f u s -i o n on rumen m o t i l i t y . D espite t h e i r own f i n d i n g s t h a t duodenal a c i d i f i c a t i o n caused g r e a t e r i n h i b i t i o n of rumen pressure changes than intravenous i n f u s i o n of s e c r e t i n a t a 58 high l e v e l acknowledged to be unphysiological, they state that "the major portion of rumen contraction i n h i b i t i o n i n sheep following duodenal a c i d i f i c a t i o n may be attributed to i n t e s t i n a l hormones". Rather than implicating the nervous system i n t h i s mechanism they suggest that the greater e f f e c t of the acid infusion may have been the r e s u l t of secretin and cholecystokinin (CCK) acting as agonists. However, CCK has been shown to have a stimulatory rather than an i n h i b i t o r y e f f e c t on g a s t r i c musculature (Grossman, 1974; Makhlouf, 1974). Intraduodenal infusion of hydrochloric acid has been shown to have marked effects on g a s t r i c myoelectrical a c t i v i t y . Using human subjects, Roze (1975) reported that the intraduo-denal infusion of hydrochloric acid solutions rapidly effected a slowing i n the ECA frequency. However, i t was noted that t h i s e f f e c t began to return to normal values despite contin-uation of the acid infusion. This occurrence, i t was theorized, resulted from ne u t r a l i z a t i o n of the infused acid by a l k a l i n e secretion from the pancreas and l i v e r i n response to the acid s t i m u l i . Hunt and Knox (1962) proposed that control of g a s t r i c emptying i s mediated by an acid t i t r a t i n g mechanism i n the duodenum. They found that the degree of i n h i b i t i o n of gas-t r i c emptying was not dependent on the pH of the g a s t r i c contents per se but on the amount of t i t r a t a b l e acid emptied into the duodenum. They suggested that rather than an osmo-receptor that detected a threshold pH of approximately 6.0 59 would t r i g g e r a r e d u c t i o n i n g a s t r i c emptying. The r e c e p t o r would d e t e c t i n t r a d u o d e n a l a c i d and cause the r e l e a s e o f s e c r e t i n , r e s u l t i n g i n b i c a r b o n a t e s e c r e t i o n from the pan-creas : and Brunner*s glands. The a c i d i n the duodenum would be n e u t r a l i z e d and the g a s t r i c i n h i b i t o r y mechanism would then cease. T h i s would f a c i l i t a t e the e n t r y of more a c i d i n t o the duodenum and the c y c l e would then r e p e a t . A c c o r d i n g to t h i s model a constant amount of a c i d would enter the duodenum and depending on i t s c o n c e n t r a t i o n , o n l y the volume of d i g e s t a from the p y l o r u s would va r y . T h i s was supported by the work of Cooke (1974) who a l s o observed t h a t the amount of a c i d e n t e r i n g the duodenum was remarkably constant and that the g a s t r i c i n h i b i t o r y mechanism was extremely s e n s i t i v e to duodenal i n f l u x of a c i d . In f u r t h e r experiments (Hunt and Knox, 1969) found t h a t the r e c e p t o r system t i t r a t e s the a l i q u o t s of a c i d e n t e r i n g the duodenum to pH 6.5. They suggested a l s o t h a t the i n h i b i t o r y e f f e c t on g a s t r i c emptying i s p r o p o r t i o n a l to the amount of base r e q u i r e d f o r n e u t r a l i z a t i o n . The n e u r a l components of such a system were not d i s c u s s e d . The i n h i b i t o r y e f f e c t on rumen m o t i l i t y o f i n t r a d u o d e n a l i n f u s i o n of l a c t i c a c i d a t the v a r i o u s c o n c e n t r a t i o n s and pH l e v e l s i n t h i s study supplements the type of model proposed by Hunt and Knox (1969). The h i g h e r c o n c e n t r a t i o n o f a c i d (0.7 M) g e n e r a l l y had a more pronounced i n h i b i t o r y e f f e c t than the lower one (0.15 M) a t the same pH. The i n h i b i t o r y 60 e f f e c t was n o t i c e a b l y l e s s pronounced a t the higher pH l e v e l i n both cases, presumably because there were fewer hydrogen ions i n the duodenal contents to be n e u t r a l i z e d to the t h r e s h o l d l e v e l . However the f a c t t h a t the h i g h e r concen-t r a t i o n of a c i d produced a g r e a t e r i n h i b i t o r y e f f e c t a t the same pH does not n e c e s s a r i l y i n f e r the e n t i r e t y of t h i s heightened e f f e c t i s due s o l e l y to a c i d i c e f f e c t s . I t i s p o s s i b l e t h a t the osmotic stimulus of the concentrated s o l u -t i o n s exerted i n h i b i t o r y e f f e c t s as w e l l . D e s p i t e the f a c t t h a t osmoreceptors and- pH r e c e p t o r s are thought to be ana-t o m i c a l l y d i f f e r e n t e n t i t i e s (Cooke, 1975).it does not pre-clude the p o s s i b i l i t y t h a t they may induce s i m i l a r e f f e c t s . S e c r e t i n and CCK are the two major hormones known to r e g u l a t e p a n c r e a t i c s e c r e t i o n s . CCK alone i s but a weak st i m u l a n t of b i c a r b o n a t e s e c r e t i o n , however i t g r e a t l y poten-t i a t e s s e c r e t i n induced p a n c r e a t i c b i c a r b o n a t e s e c t i o n . For example, work by Meyer e t a l . (1971) wi t h dogs showed t h a t the s m a l l amounts of s e c r e t i n r e l e a s e d by duodenal a c i d i f i c a -t i o n which produce minimal b i c a r b o n a t e s e c r e t i o n alone, pro-duce near maximal l e v e l s i n c o n j u n c t i o n w i t h moderate phys-i o l o g i c a l doses of CCK. Working on dogs, Grossman and Konturek (1974) found t h a t p a n c r e a t i c b i c a r b o n a t e s e c r e t i o n became maximal when the g a s t r i c contents and thus chyme e n t e r i n g the duodenum were i n t r a g a s t r i c a l l y t i t r a t e d to pH 3.0 or lower by exogenous b u f f e r s . The t h r e s h o l d l e v e l of p a n c r e a t i c b i c a r b o n a t e s e c r e t i o n was found to occur a t a 61 duodenal pH of 4.5. They concluded t h a t i n t r a d u o d e n a l a c i d p l a y s a s i g n i f i c a n t r o l e i n r e g u l a t i o n o f p a n c r e a t i c b i c a r -bonate s e c r e t i o n d e s p i t e low l e v e l s of s e c r e t i n , presumably v i a CCK p o t e n t i a t i o n . In view of the complex i n t e r r e l a t i o n s h i p s between n e u r a l , hormonal and duodenal a c i d f a c t o r s i n the r e g u l a -t i o n of g a s t r i c m o t i l i t y i t i s a p p r o p r i a t e a t t h i s p o i n t to r e l a t e these to the f i n d i n g s of t h i s study. The c o n t r o l mechanisms p r e v i o u s l y d i s c u s s e d do not adequately e x p l a i n the mechanics of m o t i l i t y r e g u l a t i o n by the duodenum. There-f o r e , based on the r e s u l t s o f t h i s study and p e r t i n e n t l i t -e r a t u r e the f o l l o w i n g mechanism i s proposed which might ex-p l a i n the s e q u e n t i a l events i n v o l v e d i n t h i s mechanism. A c i d e n t e r i n g the duodenum lowers the pH of the duo-denal contents p a s t a t h r e s h o l d l e v e l below which the r e l e a s e o f s e c r e t i n and CCK i s t r i g g e r e d as p o s t u l a t e d by Grossman and Konturek (1974). These hormones are r e l e a s e d i n concen-t r a t i o n s such t h a t d i r e c t e f f e c t s on g a s t r i c m o t i l i t y are minimal (Cooke and C l a r k e , 1976). However, the n e u r a l com-ponent of t h i s e n t e r o g a s t r i c mechanism would produce a r e f l e x i n h i b i t i o n of g a s t r i c m o t i l i t y v i a the parasympathetic ner-vous system alone (Svendsen, 1973; T i t c h e n , 1958.and 1960; Duncan, 1953) or i n c o n j u n c t i o n with the sympathetic system (Cooke and C l a r k e , 1976; Schapiro and Woodward, 1959). The r o l e of s e c r e t i n p o t e n t i a t e d by CCK would t h e r e f o r e be p r i -m a r i l y the s t i m u l a t i o n of p a n c r e a t i c b i c a r b o n a t e s e c r e t i o n which would n e u t r a l i z e the duodenal a c i d . Thus the a c i d i c 62 stimulus f o r hormone s e c r e t i o n and n e u r a l i n h i b i t i o n of m o t i l i t y would be e l i m i n a t e d . The t i t r a t i o n of the duodenal contents above the t h r e s h o l d l e v e l would f a c i l i t a t e e n t r y of another l o a d of a c i d i c d i g e s t a i n t o the duodenum and the c y c l e would repeat. The r a p i d response of the rumen smooth muscle to i n t r a -duodenal a c i d i f i c a t i o n (Experiments 1 - 1 7 ) adds credance to the proposed n e u r a l component i n the e n t e r o g a s t r i c r e f l e x i n the ovine s p e c i e s . However the r e c o v e r y and iinhibitory phases subsequent to the i n i t i a l drop i n m o t i l i t y remain un-e x p l a i n e d . I t i s p o s s i b l e t h a t these p e r i o d s r e f l e c t a r a p i d c y c l i n g of the e n t e r o g a s t r i c r e f l e x . I f t h i s were the case, p a n c r e a t i c b i c a r b o n a t e s e c r e t i o n s and the l e v e l s of the hormones governing these s e c r e t i o n s would n e c e s s a r i l y f l u c -t u a t e on a time course s i m i l a r to the m o t i l i t y changes. Horn and. Huber (1975) have, examined the e f f e c t s of i n t r a d u o d e n a l l a c t i c a c i d (.7 M pH 2.0) i n f u s i o n on the flow r a t e and b i c a r b o n a t e content o f p a n c r e a t i c - b i l e duct s e c r e t i o n s i n sheep. The responses obtained were monophasic and no p r e c i p i t o u s f l u c -t u a t i o n s i n b i c a r b o n a t e flow r a t e or output were r e p o r t e d over the 70 min experimental p e r i o d . I n f u s i o n s o f s e c r e t i n or CCK a l s o generated uniform monophasic responses of b i c a r -bonate flow r a t e and content from the p a n c r e a t i c - b i l e duct. Byrnes and Marjason (1976) have developed a s e n s i t i v e s p e c i f i c radioimmunoassay f o r s e c r e t i n i n man. The r e l e a s e of s e c r e t i n r e s u l t i n g from i n t r a d u o d e n a l i n f u s i o n of hydro-63 c h l o r i c a c i d f o r 20 min was a l s o monophasic and no r a p i d f l u c t u a t i o n s i n plasma hormone l e v e l s were seen d u r i n g or subsequent t o the i n f u s i o n . The evidence presented above tends to preclude the p o s s i b i l i t y t h a t the p h a s i c m o t i l i t y response to duodenal a c i d i f i c a t i o n seen i n t h i s study r e -s u l t s from a r a p i d c y c l i n g o f the e n t e r o g a s t r i c r e f l e x . The p o s s i b i l i t y t h a t the a c i d r e c e p t o r s simply become r e f r a c t o r y to the a c i d s timulus might e x p l a i n the recover y p e r i o d s observed i n these experiments. However, the mech-anism whereby the r e c e p t o r s would escape from t h i s r e f r a c t o r y p e r i o d d e s p i t e a constant a c i d stimulus i s d i f f i c u l t to en-v i s i o n . The r e s u l t s of t h i s study a l s o p r e c l u d e the p o s s i b i l i t y t h a t the ph a s i c m o t i l i t y response to l a c t i c a c i d i s merely a normal v a r i a b i l i t y i n a c t i v i t y . F i r s t l y , t h i s p o s s i b i l i t y i s u n l i k e l y because a recover y p e r i o d f o l l o w e d the i n i t i a l i n h i b i t o r y p e r i o d on e s s e n t i a l l y the same time course, as shown i n F i g u r e s 3 and 4. T h i s c o n s i s t e n c y of t h i s response does not support a v a r i a b i l i t y model. Secondly, these f l u c t u a t i o n s i n m o t i l i t y which o f t e n exceeded 100% of the p r e i n f u s i o n mean o c c u r r e d i n a p h a s i c manner onl y a f t e r the in t r a d u o d e n a l a c i d i n f u s i o n but not d u r i n g the p r e i n f u s i o n p e r i o d o r d u r i n g the s a l i n e i n f u s i o n experiments ( i . e . , F i g u r e 8). T h i s i n d i c a t e s t h a t the response was the d i r e c t r e s u l t o f duodenal a c i d i f i c a t i o n . T h i r d l y , the experiments i n which the g r e a t e s t amount of t i t r a t a b l e a c i d was i n f u s e d , showed the l e a s t r e c o v e r y of m o t i l i t y , which i n d i c a t e s a dose r e l a t e d response to the s t i m u l u s . L a s t l y , t o t a l a b o l i -t i o n of a s e n s i t i v e n e u r a l l y and/or hormonally c o n t r o l l e d p h y s i o l o g i c a l a c t i v i t y f o r extended p e r i o d s of time r e -q u i r e s e i t h e r the i n h i b i t i o n of a s t i m u l a t o r y mechanism or s t i m u l a t i o n o f an i n h i b i t o r y mechanism. Thus i t i s u n l i k e l y t h a t r e c u r r e n t change ' i n rumen m o t i l i t y from 0 to 100% of p r e i n f u s i o n a c t i v i t y i s a t t r i b u t e d merely to random v a r i a -t i o n s . F u r t h e r experiments need to be undertaken to e x p l a i n t h i s o s c i l l a t o r y m o t i l i t y a c t i v i t y of the rumen f o l l o w i n g duodenal a c i d i f i c a t i o n . The c o n t i n u a t i o n of the p h a s i c a c t i v i t y f o l l o w i n g t e r -m i n a t i o n of the i n f u s i o n i n d i c a t e s t h a t u n n e u t r a l i z e d a c i d remained i n the duodenum. In sheep the common p a n c r e a t i c -b i l e duct i s l o c a t e d approximately 30 cm from the p y l o r u s (Frandson, 1974). T h e r e f o r e a c i d e n t e r i n g the i n t e s t i n e from the i n f u s i o n cannulae presumably would not be f u l l y n e u t r a l i z e d u n t i l the proximal contents had reached the more d i s t a l l y l o c a t e d duct. Thus some minutes a f t e r t e r m i n a t i o n o f the i n f u s i o n the m o t i l i t y of the rumen remained a l t e r e d . I t can be seen from F i g u r e 3. t h a t the escape from the m o t i l i t y d e p r e s s i o n was very r a p i d f o l l o w i n g the p h a s i c a c t i v i t y t h a t o c c u r r e d subsequent to i n f u s i o n t e r m i n a t i o n . Presumably t h i s would c o i n c i d e w i t h the n e u t r a l i z a t i o n o f the l a c t i c a c i d i n the duodenum above the i n h i b i t o r y t h r e s -h o l d . 65 In t r a r u m i n a l A d m i n i s t r a t i o n of L a c t i c A c i d In h e a l t h y animals l a c t i c a c i d produced i n the rumen by l a c t o b a c i l l i i s metabolized immediately by other rumen microbes ( i . e . , P eptostreptococcus e l s d e n i i and protozoans) and t h e r e -f o r e i s not found i n s i g n i f i c a n t c o n c e n t r a t i o n i n the d i g e s t a (Dunlop, 19 72). However, upon i n g e s t i o n of l a r g e q u a n t i t i e s of a hi g h energy f e e d s t u f f the rumen pH drops, due i n i t i a l l y to a r i s e i n d i g e s t a VFA c o n c e n t r a t i o n (Dirksen, 1970; Mackenzie, 1967; Dunlop, 1972). The rumen environment becomes u n s u i t a b l e f o r r a p i d growth of f l o r a o ther than l a c t o b a c i l l i which produce copious q u a n t i t i e s o f l a c t i c a c i d r e s u l t i n g i n gene r a l a c i d o s i s . The rumen c o n c e n t r a t i o n o f l a c t i c a c i d i n l a c t i c a c i d o -s i s tends to vary c o n s i d e r a b l y . L e v e l s from 2.2 mM/1 a s s o c i a -ted with high l e v e l s of v o l a t i l e f a t t y a c i d s (Dirksen, 1970) to more than 30 0 mM/1 (Bond, 1959) have been r e p o r t e d . P h i l l i p s o n and McAnnally (1942) i n t r o d u c e d s o l u t i o n s c o n t a i n i n g 0.16 and 0.32 moles l a c t a t e i n t r a r u m i n a l l y and found rumen l a c t i c a c i d l e v e l s i n c r e a s e d from 0 to 13 mM/1 and 51 mM/1, r e s p e c t i v e l y . In t h i s study (Experiments 32-34) s o l u t i o n s c o n t a i n i n g 0.15 and 0.70 moles l a c t i c a c i d were i n t r o d u c e d i n t o the rumen. The l o c a t i o n o f the t i p s of the i n f u s i o n cannulae immediately beneath the e l e c t r o d e p a i r s (animals #1 and #2) and p r o x i m i t y o f the f i s t u l a (animal #3) to the e l e c t r o d e 6 6 p a i r s e n s u r e d t h a t t h e c o n c e n t r a t i o n o f a c i d i n t h e v i c i n i t y o f t h e r e c o r d i n g a r e a w a s s i m i l a r t o t h a t o c c u r r i n g i n t h e d i s e a s e . I n e a c h o f t h e t h r e e e x p e r i m e n t s p r e s e n t e d , t h e s o l u t i o n s e x e r t e d n o i n h i b i t o r y e f f e c t o n r u m e n m y o e l e c t r i -c a l a c t i v i t y . T h i s s u p p o r t s t h e f i n d i n g s o f o t h e r s ( A s h , 1 9 5 9 ; H u b e r , 1 9 7 6 ) t h a t l a c t i c a c i d d o e s n o t i n d u c e r u m e n s t a s i s b y d i r e c t a c t i o n o n t h e r u m e n v i s c u s . I n t r a v e n o u s A d m i n i s t r a t i o n o f L a c t i c A c i d T h e p o s s i b i l i t y t h a t l a c t i c a c i d e x e r t s a n i n h i b i t o r y e f f e c t o n r u m e n m o t i l i t y f o l l o w i n g a b s o r p t i o n i n t o t h e b l o o d -s t r e a m w a s i n v e s t i g a t e d b y t h e i n t r a v e n o u s i n f u s i o n o f v a r y -i n g c o n c e n t r a t i o n s o f s o d i u m l a c t a t e . D u n l o p ( 1 9 6 1 ) s h o w e d t h a t t h e u n d i s s o c i a t e d r a t h e r t h a n t h e a n i o n i c f o r m o f t h e a c i d w a s a b s o r b e d f r o m t h e r u m e n . A h r e n s ( 1 9 6 7 ) s h o w e d t h a t a b s o r p t i o n o f l a c t i c a c i d f r o m t h e r u m e n w a s d e p e n d e n t o n r u m e n m o v e m e n t . R u m e n s t a s i s p r e v e n t e d a b s o r p t i o n o f t h e a c i d . T h u s D u n l o p ( 1 9 7 2 ) h y p o t h e s i z e d t h a t t h e r u m e n s t a s i s m a y a c t t o m i n i m i z e t h e m e t a b o l i c a c i d o s i s t h a t a c c o m p a n i e s r u m e n a c i d o s i s . B r o b e r g ( 1 9 6 0 ) h a s s h o w n t h a t l a r g e i n c r e a s e s i n b l o o d l a c t a t e f o l l o w e d i n t r a d u o d e n a l a d m i n i s t r a t i o n o f l a c t i c a c i d s o l u t i o n s a t p H 3 . 2 i n s h e e p . D u n l o p ( 1 9 7 2 ) s t a t e d t h a t t h e u n d i s s o c i a t e d f o r m o f t h e a c i d w a s m o s t r a p i d l y a b s o r b e d f r o m t h e i n t e s t i n e . T h e b l o o d l a c t i c a c i d l e v e l s m a y r e a c h 2 4 0 mg% i n s e v e r e a c i d o s i s ( H y l d g a a r d - J e n s e n a n d S i m e s e n , 1 9 6 6 ) a s c o m p a r e d t o n o r m a l v a l u e s o f 9 - 1 9 mg% i n h a y f e d sheep (Annison et a l . , 1959). Filippova (1973) has shown that l a c t i c acid introducer into the i n t e s t i n a l a r t e r i e s of cat bowel preparations increased the number of afferent impulses i n the i n t e s t i n a l nerves. This suggests a possi-ble blood lactate level-neural i n t e r a c t i o n . Experiments i n t h i s study involved the infusion of racemic lactate solutions into the jugular veins of sheep. The concentrations used increased the lactate i n the blood by approximately 20 and 180 mg%. The h a l f - l i f e ( t 1 / 2 ) of lactate i n the sheep blood i s 22 minutes for the L-isomer and much longer for the D-isomer (Dunlop and Hammond, 196 5) i n d i c a t i n g that the blood lactate l e v e l s i n these experiments remained elevated for some time. Despite t h i s , no i n h i b i t i o n of rumen m o t i l i t y was seen up to 1 hr following infusion termination. It i s not u n t i l the rumen pH f a l l s below f i v e that s i g n i f i c a n t amounts of l a c t i c acid are absorbed from the gut. This absorptive process i s a r e l a t i v e l y slow process (Mackenzie, 1 9 6 7 ) . However, marked rumen s t a s i s generally occurs well before the pH l e v e l i s attained (Dunlop, 1 9 7 2 ) . Thus upon consideration of these facts and the findings of the I.V. infusion studies i t i s u n l i k e l y that high blood levels of lactate induce rumen s t a s i s . 68 SUMMARY AND CONCLUSIONS The experiments conducted on sheep i n t h i s study examined the i n t e r r e l a t i o n s h i p s o f s e v e r a l p h y s i o l o g i c a l parameters of normal ruminal a c t i v i t y and the m o t i l i t y changes caused by the i n t r o d u c t i o n of l a c t i c a c i d v i a v a r -ious r o u t e s . M y o e l e c t r i c a l a c t i v i t y and pressure changes i n the rumen were recorded over extended p e r i o d s to enable the d e t e r m i n a t i o n of c o r r e l a t i o n s among the rumen spike b u r s t d u r a t i o n , magnitude and frequency parameters. The r e s u l t s showed t h a t a l l the parameters a c c u r a t e l y r e f l e c t rumen m o t i l i t y and any changes t h e r e i n . The s t r o n g e s t degree o f c o r r e l a t i o n e x i s t e d w i t h i n the m y o e l e c t r i c a l and w i t h i n the pressure change parameters. Spike b u r s t d u r a t i o n was d e t e r -mined to be the most s e n s i t i v e i n d i c a t o r o f rumen m o t i l i t y and t h e r e f o r e was u t i l i z e d as the c r i t e r i o n f o r examination o f l a c t i c a c i d induced m o t i l i t y changes. I t was found t h a t rumen m o t i l i t y was not a f f e c t e d by i n t r a r u m i n a l i n t r o d u c t i o n of 1000 ml o f 0.15 or 0.7 M l a c t i c a c i d a t pH 2.0. T h i s r e s u l t supports the theory t h a t i n t r a -ruminal l a c t i c a c i d i s not the cause of rumen s t a s i s i n l a c -t i c a c i d o s i s . The p o s s i b i l i t y t h a t l a c t i c a c i d e n t e r i n g the i n t e s -t i n e e x e r t s an i n h i b i t o r y e f f e c t on rumen m o t i l i t y was a l s o i n v e s t i g a t e d . S o l u t i o n s o f 0.15 and 0.7 M l a c t i c a c i d (250 ml) a t pH 2.0, 4.0 and 6.0 were i n f u s e d i n t o the p r o x i -69 mal duodenum v i a permanently implanted cannulae. Profound i n h i b i t i o n o f rumen m o t i l i t y o c c u r r e d immediately a f t e r l a c t i c a c i d at pH 2.0 was i n f u s e d . T h i s s h o r t p e r i o d of i n h i b i t i o n was f o l l o w e d by a recovery of m o t i l i t y which g e n e r a l l y was g r e a t e r when lower c o n c e n t r a t i o n s of l a c t i c a c i d were i n f u s e d than higher ones. T h i s i n i t i a l r e c o v e r y phase was f o l l o w e d by f u r t h e r i n h i b i -t o r y and recover y phases. A r a p i d escape from t h i s o s c i l l a -t o r y rumen m o t i l i t y o c c u r r e d up to an hour f o l l o w i n g the t e r m i n a t i o n o f i n f u s i o n . S i m i l a r , yet somewhat reduced, responses were seen with the s o l u t i o n s a t pH 4.0 and 6.0. These responses were a t t r i b u t e d to e n t e r o g a s t r i c r e f l e x e s which probably a c t v i a s y n e r g i s t i c hormonal and n e u r a l mechanisms. Intravenous i n f u s i o n o f 2 l e v e l s o f l a c t a t e which i n -creased blood l a c t a t e l e v e l s by approximately 20 mg% and 180 mg%, r e s p e c t i v e l y . D e s p i t e the f a c t t h a t l a r g e q u a n t i -t i e s o f a c i d are absorbed from the g a s t r o i n t e s t i n a l t r a c t i n t o the blood i n animals s u f f e r i n g from l a c t i c a c i d o s i s , the i n h i b i t i o n o f rumen m o t i l i t y by the systemic route i s u n l i k e l y . I t may be concluded t h a t the i n t r o d u c t i o n o f l a c t i c a c i d i n t o the duodenum exerted a strong i n h i b i t o r y e f f e c t on rumen m o t i l i t y and t h a t i n h i b i t o r y e f f e c t s o f i n t r a -ruminal and intravenous i n f u s i o n were absent. These r e s u l t s suggest t h a t i n h i b i t i o n o f rumen m o t i l i t y i n 70 l a c t i c a c i d o s i s may be caused p r i m a r i l y by l a c t i c a c i d pro-duced i n the rumen e n t e r i n g the i n t e s t i n e and c a u s i n g a s t i m u l a t i o n of the e n t e r o g a s t r i c r e f l e x e s . 71 BIBLIOGRAPHY Ahrens, F.A. (1967). Histamine, l a c t i c a c i d and h y p e r t o n i c i t y as f a c t o r s i n the development of r u m i n i t i s i n c a t t l e . Am. J . Bet. Res. 28: 1335-1342. Anderson, S. (1974). Bulbogastione. In G a s t r o i n t e s t i n a l Hormones, p. 555-562. J.C. Thompson ( E d i t o r ) , U n i v e r -s i t y of Texas P r e s s . Andrews, C.J.H., and Andrews, W.H.H. (1971). Receptors ac-t i v a t e d by a c i d i n the duodenal w a l l o f r a b b i t s . Quart. J . Expt. P h y s i o l . 56: 221-230. Annison, E.F., Lewis, D., and Lindsay, D.B. (1959). 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N.J. 84 APPENDIX 85 APPENDIX I ANIMAL PREPARATIONS Animal Sex Weight S u r g i c a l P r e p a r a t i o n s 1 F 55 kg I n t r a r u m i n a l p o l y e t h y l e n e i n f u s i o n cannula ( v e n t r a l sac) I n t r a r u m i n a l f l u i d - f i l l e d b a l l o o n - t i p p e d tygon tube a t t a c h e d t o pr e s s u r e t r a n s -ducer ( v e n t r a l sac) 2 p a i r s f i n e needle platinum e l e c t r o d e s 250 y) ( s e r o s a l s u r f a c e of rumen v e n t r a l sac) Intraduodenal p o l y e t h y l e n e i n f u s i o n cannu-l a ( t i p 8 cm from pylorus) Intraduodenal p o l y e t h y l e n e i n f u s i o n cannu-l a ( l e f t j u g u l a r ) 2 F 56 kg As above 3 M 5 6 kg Rumen f i s t u l a ( d o r s a l sac) which allowed passage of f l u i d f i l l e d b a l l o o n - t i p p e d tygon tube a t t a c h e d t o pr e s s u r e t r a n s -ducer and i n f u s i o n o f s o l u t i o n s . 2 p a i r s f i n e needle platinum e l e c t r o d e s (250 y) ( s e r o s a l s u r f a c e of rumen v e n t r a l sac) Re-entrant cannula i n duodenum immediately d i s t a l to p y l o r u s - f a c i l i t a t e d i n f u s i o n of s o l u t i o n s and d i g e s t a c o l l e c t i o n . 86 APPENDIX I I E f f e c t s of Intraduodenal, I n t r a r u m i n a l and  Intravenous L a c t i c A c i d I n f u s i o n on Rumen Spike Burst D u r a t i o n The F i g u r e s presented on the f o l l o w i n g pages are r e p r o -d u c t i o n s of computer p l o t s which show the e f f e c t s of l a c t i c a c i d i n f u s e d i n t r a d u o d e n a l l y , i n t r a r u m i n a l l y and i n t r a v e n -o u s l y on rumen m o t i l i t y . The X a x i s d e p i c t s time i n minutes and the Y a x i s shows spi k e b u r s t d u r a t i o n expressed as a percentage of the p r e i n f u s i o n mean. The arrows i n d i c a t e the beginning and t e r m i n a t i o n o f the i n f u s i o n s . Experiment 1. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 2.0) on rumen s p i k e b u r s t d u r a t i o n (animal #1). Experiment 2. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n o f 0.15 M l a c t i c a c i d (pH 2.0) on rumen s p i k e b u r s t d u r a t i o n (animal #1). 200 Experiment 3. E f f e c t o f i n r a d u o d e n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 2.0) on rumen s p i k e b u r s t d u r a t i o n (animal #1). Experiment 4. E f f e c t of i n t r a d u o d e n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #3). VO o 200 Experiment 5. E f f e c t of i n t r a d u o d e n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 2.0) on rumen s p i k e b u r s t d u r a t i o n (animal #3). 200 Experiment 6. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n : (animal #1). 200 h 175 r 105 120 Experiment 7. E f f e c t of i n t r a d u o d e n a l i n f u s i o n o f 0.15 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #1). 200 Experiment 8. E f f e c t of intraduodenal infusion of 0.15 M l a c t i c acid (pK 2.0) on rumen spike burst duration (animal #3). 200 Experiment 9. E f f e c t of i n t r a d u o d e n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #1). 200 175 -Z 150 -105 120 Time (min) Experiment 10. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #1). Experiment 11. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n o f 0.7 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #1). Experiment 12. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n o f 0.7 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #1). 200 Experiment 13. E f f e c t of i n t r a d u o d e n a l i n f u s i o n of 0.7 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #3). 200 Experiment 14. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n of 0.7 M l a c t i c a c i d (pK 2.0) on rumen spike b u r s t d u r a t i o n (animal #3). Experiment 15. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n . o f 0.7 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #3). 200 Experiment 16. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n of 0.7 M l a c t i c a c i d (pK 2.0) on rumen spike b u r s t d u r a t i o n (animal #3). Experiment 17. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n o f 0.7 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #1 ) . Experiment 18. E f f e c t of i n t r a d u o d e n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 4.0) on rumen spike b u r s t d u r a t i o n (animal #1). 200 Experiment 19. Effect of intraduodenal infusion of 0.15 M lactic acid (pH 4.0) on rumen spike burst duration (animal #1). 200 175 " * 150 -o 105 120 Time (min) Experiment 20. E f f e c t o f intraduodenal i n f u s i o n of 0.7 M l a c t i c a c i d (pK 4.0) on rumen spike b u r s t d u r a t i o n (animal #1). 200 175 150 125 100 75 50 25h OL -15 15 30 45 Time (min) 60 75 90 105 120 Experiment 21. E f f e c t of i n t r a d u o d e n a l i n f u s i o n of 0.7 M l a c t i c a c i d (pK 4.0) on rumen spike b u r s t d u r a t i o n (animal #3). 200 175 £ 150 125 100 75 50 25 -15 15 30 45 60 Time (min) 75 90 105 120 Experiment 22 E f f e c t of i n t r a d u o d e n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 6.0) on rumen sp i k e b u r s t d u r a t i o n (animal #1). 200 Experiment 23. E f f e c t of i n t r a d u o d e n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 6.0) on rumen spike b u r s t d u r a t i o n (animal #1). Experiment 24. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n of 0.7 M l a c t i c a c i d (pH 6.0) on rumen spike b u r s t d u r a t i o n (animal # 1 ) . 200 Exper iment 2 5. E f f e c t of in t r a d u o d e n a l i n f u s i o n of 0.7 M l a c t i c a c i d (pH 6.0) on rumen spike b u r s t d u r a t i o n (animal #3). 200 Experiment 26. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n o f p h y s i o l o g i c a l s a l i n e on rumen sp i k e b u r s t d u r a t i o n (animal #3). 200 25 h 1 1 1 I I I I L -15 0 15 30 45 60 75 90 Time (min) Experiment 27. E f f e c t of i n t r a d u o d e n a l i n f u s i o n of p h y s i o l o g i c a l s a l i n e on rumen spike b u r s t d u r a t i o n (animal #1). 200 Experiment 28. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n of p h y s i o l o g i c a l s a l i n e on rumen s p i k e b u r s t d u r a t i o n (animal #1). 200 Experiment 29. E f f e c t of i n t r a d u o d e n a l i n f u s i o n of p h y s i o l o g i c a l s a l i n e on rumen sp i k e b u r s t d u r a t i o n (animal #3) . 200 175 <*> 150 -P 125 u 4J 100 w d QJ 75 50 25 -15 15 30 Time (min) 45 60 75 90 Experiment 30. E f f e c t of i n t r a d u o d e n a l i n f u s i o n of p h y s i o l o g i c a l s a l i n e on rumen sp i k e b u r s t d u r a t i o n (animal ff1). 200 Experiment 31. E f f e c t o f i n t r a d u o d e n a l i n f u s i o n of p h y s i o l o g i c a l s a l i n e on rumen sp i k e b u r s t d u r a t i o n (animal #1).' Experiment 32. E f f e c t o f i n t r a r u m i n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #1). oo 200 Experiment 33. E f f e c t of i n t r a r u m i n a l i n f u s i o n of 0.15 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #1). Experiment 34. E f f e c t of i n t r a r u m i n a l i n f u s i o n of 0.7 M l a c t i c a c i d (pH 2.0) on rumen spike b u r s t d u r a t i o n (animal #3). M X TJ CD H H-3 fD rt co Spike burst, d u r a t i o n (%) , — M pj NJ Hi 3 O Hi H- CD 3 3 O 0) rt 1—1 \ 3 0 Hi NJ • • — H-• 0 3 3 rt H-H 3 H ro < (D CD 3 3 3 O H-C 3 CO CO — TS H- H-*T 3 fD Hi cr to c H-0 CO 3 r+ O DJ HI i-i CO CU 0 rt Oi H-o 3 3 I—1 fl> O rt fl) rt CD cn Co O O ~[— NJ Cn cn O cn o o NJ cn cn o cn NJ O O IZ I 200 Experiment 36. E f f e c t of intravenous i n f u s i o n of sodium l a c t a t e (20 mg/ml) on rumen spike b u r s t d u r a t i o n (animal #1.) . Experiment 37. E f f e c t of intravenous i n f u s i o n of sodium l a c t a t e ( 2 0 mg/ml) on rumen spike b u r s t d u r a t i o n (animal # 1 ) . 200 Experiment 38. E f f e c t of intravenous i n f u s i o n of sodium l a c t a t e (20 mg/ml) on rumen spike b u r s t d u r a t i o n (animal 200 Experiment 39. E f f e c t of intravenous i n f u s i o n of sodium l a c t a t e (180 mg/ml) on rumen sp i k e b u r s t d u r a t i o n (animal #2). Ul 200 175 r '2. 50 . 25 r r • i L i 1 -15 0 15 30 45 Time (min) Experiment 40. E f f e c t o f intravenous i n f u s i o n of sodium l a c t a t e (180 mg/ml) on rumen spike b u r s t d u r a t i o n (animal #1). 200 Experiment 41. E f f e c t o f intravenous i n f u s i o n of sodium l a c t a t e (180 mg/ml) on rumen spike b u r s t d u r a t i o n (animal #2). 200 175 -150 " o •H 25 " 0 -I i i i i l -15 0 15 30 45 Time (min.) Experiment 42. E f f e c t of intravenous i n f u s i o n of sodium l a c t a t e (180 mg/ml) on rumen spike b u r s t d u r a t i o n (animal #3). 200 200 Experiment 44. E f f e c t o f intravenous i n f u s i o n of p h y s i o l o g i c a l s a l i n e on rumen spike b u r s t d u r a t i o n (animal #3) . 

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