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Effect of D i p y r i d a m o l e on the G l y c o g e n M e t a b o l i s m in the N o r m a l and I s c h e m i c Canine M y o c a r d i u m I n t h e p r e c e d i n g p a p e r 1, we r e p o r t e d t h a t p r e t r e a t m e n t of t h e dog w i t h n i t r o g l y c e r i n i n h i b i t e d t h e r a t e of accelera t i o n of u t i l i z a t i o n of m y o c a r d i a l glycogen i n d u c e d b y l i g a t i o n of t h e c o r o n a r y a r t e r y . I n t h e p r e s e n t s t u d y , t h e effect of d i p y r i d a m o l e o n t h e m y o c a r d i a l u t i l i z a t i o n of glycogen a n d levels of h i g h - e n e r g y p h o s p h a t e c o m p o u n d s were i n v e s t i g a t e d . D i p y r i d a m o l e was c h o s e n b e c a u s e i t is r e l a t i v e l y ineffective a g a i n s t a n g i n a l a t t a c k , inspire of h a v i n g a p o w e r f u l c o r o n a r y d i l a t i n g action~, a. Since n i t r o g l y c e r i n is t h e m o s t effective a n t i a n g i n a l a g e n t , inspite of h a v i n g o n l y a m o d e r a t e c o r o n a r y d i l a t i n g a c t i o n ~,~, we e x p e c t e d t h a t t h e effect of d i p y r i d a m o l e on the myocardial metabolism during coronary ligation would p r o b a b l y b e d i f f e r e n t f r o m t h a t of n i t r o g l y c e r i n . T h e m e t h o d s e m p l o y e d in t h e p r e s e n t s t u d y are t h e s a m e as d e s c r i b e d in o u r p r e c e d i n g r e p o r t ~. M o n g r e l dogs a n e s t h e t i z e d w i t h p e n t o b a r b i t a l were used. I n e x p e r i m e n t s w i t h i s c h e m i c h e a r t s , o n e of t h e s m a l l b r a n c h e s of t h e left c o r o n a r y a r t e r y was l i g a t e d 5 m i n a f t e r i.v. i n j e c t i o n of saline or d i p y r i d a m o l e (250 ~xg/kg). T h e h e a r t s were r e m o v e d 1.5, 3, 7, or 30 m i n a f t e r t h e c o r o n a r y ligation, a n d i m m e d i a t e l y frozen w i t h freezing clamps. T h e e n d o - a n d e p i c a r d i a l p o r t i o n s of t h e left v e n t r i c u l a r wall, w h i c h h a d b e e n p e r f u s e d b y t h e l i g a t e d c o r o n a r y a r t e r y , were c a r e f u l l y t a k e n for d e t e r m i n a t i o n of glycogen, glucose-6p h o s p h a t e (G6P), l a c t a t e , a d e n o s i n e t r i p h o s p h a t e (ATP) a n d p h o s p h o c r e a t i n e (PCr), a n d a c t i v i t i e s of p h o s p h o rylase a a n d a + b. I n e x p e r i m e n t s w i t h n o n - i s c h e m i c h e a r t s , t h e h e a r t s were r e m o v e d 5 m i n a f t e r t h e i n j e c t i o n w i t h o u t l i g a t i o n of t h e c o r o n a r y a r t e r y . Results. R e s u l t s are s h o w n in t h e F i g u r e a n d t h e Table. Since t h e results c o n c e r n i n g t h e c o n t r o l (salineinjected) dogs were e s s e n t i a l l y t h e s a m e as t h o s e o b t a i n e d in o u r p r e c e d i n g s t u d y , t h e d a t a o n c o n t r o l dogs s h o w n in t h e F i g u r e a n d t h e T a b l e are cited f r o m o u r p r e c e d i n g e x p e r i m e n t s ~.

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Experiments with non-ischemic hearts. P r e t r e a t m e n t w i t h d i p y r i d a m o l e i n f l u e n c e d n e i t h e r levels of glycogen, G6P, l a c t a t e , A T P a n d PCr, n o r a c t i v i t i e s of p h o s p h o rylase a a n d a + b, i n e a c h of t h e e n d o - a n d e p i c a r d i a l layers of t h e left v e n t r i c l e . Experiments with ischemic hearts. P r e t r e a t m e n t w i t h d i p y r i d a m o l e m o d i f i e d t h e p a t t e r n of a c c e l e r a t i o n of glycogenolysis a n d glycolysis i n d u c e d b y t h e c o r o n a r y l i g a t i o n as d e s c r i b e d below. A f t e r t h e c o r o n a r y ligation, glycogen d e c r e a s e d t e m p o r a r i l y followed b y a s e c o n d a r y slow decrease in t h e c o n t r o l dogs, b u t in t h e d i p y r i d a m o l e i n j e c t e d dogs i t d e c r e a s e d o n l y slowly. D u r a t i o n of increase in G 6 P a f t e r t h e c o r o n a r y l i g a t i o n was r e l a t i v e l y s h o r t in t h e d i p y r i d a m o l e - i n j e c t e d dogs. T h e a n a e r o b i c l a c t a t e p r o d u c t i o n d u e t o t h e c o r o n a r y l i g a t i o n was m a r k e d l y a u g m e n t e d b y t h e p r e t r e a t m e n t w i t h dipyrid a m o l e in t h e e n d o - a n d e p i c a r d i a l layers, especially in t h e former. D u r i n g t h e c o r o n a r y ligation, A T P c h a n g e d little in t h e c o n t r o l dogs, b u t in t h e p r e s e n c e of d i p y r i d a m o l e it s l i g h t l y decreased. B o t h t h e e n d o - a n d e p i c a r d i a l P C r levels d e c r e a s e d slowly a f t e r t h e c o r o n a r y ligation, followed b y a g r a d u a l i n c r e a s e in t h e c o n t r o l dogs; b u t in t h e p r e s e n c e of d i p y r i d a m o l e , t h e s e levels d e c r e a s e d r a p i d l y a f t e r t h e c o r o n a r y l i g a t i o n w i t h o u t a following increase. A c t i v i t y of l J h o s p h o r y l a s e a in t h e e n d o - a n d e p i c a r d i a l layers i n c r e a s e d m a r k e d l y a f t e r t h e c o r o n a r y l i g a t i o n in t h e c o n t r o l dogs, b u t in t h e p r e s e n c e of d i p y r i d a m o l e i t did n o t increase m a r k e d l y .

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