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On the delayed antiischaemic action of PgI2 and its stable analogue 7-oxo PgI2
j Mol Cell Cardiol 17 (Supplement 3) (1985)
127PROSTACYCLIN ON CORONARY THROMBOSIS AND MYOCARDIAL ISCHEMIA IN CONSCIOUS CANINE EXPERIMENTS. V . B . F i e d l e r , M.Nardin, Dept.Pharmacology, Bayer AG, Wuppertal, F.R.G. The effects of intravenhricular prostacyclin (PGIT;50,100 ng/kg/min) infusion on hemodynamics, the ECG, coronary thrombosis and myocardial ischemia (MI) were studied in chronically equipped conscious dogs and compared with drug vehicle Tris-HC1. Coronary thrombosis was induced by electrical stimulation of an artery over a wire for 6h. PGI? at i00 ng/kg/min decreased BP by 24+3~(p<0.01) for 5h, increased HR at lh by 28+_~%(p<0.05) followed by a decrease, ~ d elevated CO by 41~5%(p
128LEUKOTRIENES ON PORCINE HEMODYNAMICS AND PROSTANOID RELEASE. V.B.Fiedler, M.Mardin, ~.J.Gardiner I, T.S.Abram I. Dept.'s Pharmacology, Bayer AG, Wuppertal, F.R.G., and Miles Lab., Slough, G.B. We studied the effects of i.c. leukotriene BA, Ca, D a and Ea(O.1-3 pg) on coronary blood flow and resistance in anesthetized pi~s. Conv6ntionaI hemodynamics were measured and the ECG was obtained in lead II. TxB 2 and 6-PGFl~were measured during LT effects on the heart. All LT's except LTB~ reduced coronary flow. Peak reduction was produced by 3 us of 9 9 ~ e,+ 0r+ 0r+ . , ~ each elcosanold: C,= 96+4,0 ; D,= 98+2,~ ; E,= 82+8,~ . Coronary reslstance increased by Oh= 65+18,~; C~= 22~+94A (p
1 2 9 ON THE D E L A Y E D A N T I I S C H A E M I C A C T I O N OF PgI 2 A N D ITS S T A B L E A N A L O G U E 7-oxo PgI 2. L. S z e k e r e s , ~ v a U d v a r y and A g n e s V~gh. D e p a r t m e n t of P h a r m a cology, U n i v e r s i t y M e d i c a l School, S z e g e d , H u n g a r y . We h a v e s h o w n that PgI 2 and its s t a b l e a n a l o g u e 7 - o x o P g I 2 - N a e x e r t s a late a n t i i s c h a e m i c e f f e c t in a d o g m o d e l of a n g i n a a p p e a r i n g 60-90 m i n a f t e r c o m p l e t i o n of i n f u s i o n w h e n b l o o d p r e s s u r e fall a n d i n h i b i t i o n of p l a t e l e t a g g r e g a t i o n w a s over. A m e ~ . b o l i c p r o t e c t i o n was f o u n d in rats p r e t r e a t e d w i t h 7 - o x o P g I 2 - N a 2 h o u r - b e f o r e e x c i s i n g the h e a r t and i n c u b a t i n g it for 1 m i n u t e in R i n g e r s o l u t i o n . T h e p r o t e c t i v e e f f e c t was also p r e s e n t in e x p e r i m e n t a l m y o c a r d i a l i n f a r c t i o n in c o n s c i o u s rats p r e t r e a ted 2 h o u r s b e f o r e o c c l u s i o n . H o w e v e r t r e a t m e n t d i d not i n c r e a s e s u r v i v a l rate and f a i l e d to r e d u c e the i n c i d e n c e and s e v e r i t y of a r r h y t h m i a s . Prol o n g e d t r e a t m e n t of dogs w i t h 7 - o x o P g I 2 - N a /250 u g / k g i.m. for 3 days/ m o d e r a t e d c h a n g e s i n d u c e d b y l i g a t i o n of the left a n t e r i o r d e s c e n d i n g cor o n a r y a r t e r y for 25 m i n u t e s , in the a n i m a l a n a e s t h e t i z e d and t h o r a c o t o m i z e d on the f o u r t h day. It r e d u c e d S T - s e g m e n t e l e v a t i o n , and i m p r o v e d b l o o d s u p p l y to the i s c h a e m i c area. D e s p i t e this m a n i f e s t a n t i i s c h a e m i c a c t i o n the i n c i d e n c e of p o s t - o c c l u s i o n a r r h y t h m i a s i n c r e a s e d . The incid e n c e of r e p e r f u s i o n a r r h y t h m i a s and t h a t of v e n t r i c u l a r f i b r i l l a t i o n w a s h o w e v e r s i g n i f i c a n t l y r e d u c e d as c o m p a r e d w i t h the n o n - t r e a t e d controls.
127PROSTACYCLIN ON CORONARY THROMBOSIS AND MYOCARDIAL ISCHEMIA IN CONSCIOUS CANINE EXPERIMENTS. V . B . F i e d l e r , M.Nardin, Dept.Pharmacology, Bayer AG, Wuppertal, F.R.G. The effects of intravenhricular prostacyclin (PGIT;50,100 ng/kg/min) infusion on hemodynamics, the ECG, coronary thrombosis and myocardial ischemia (MI) were studied in chronically equipped conscious dogs and compared with drug vehicle Tris-HC1. Coronary thrombosis was induced by electrical stimulation of an artery over a wire for 6h. PGI? at i00 ng/kg/min decreased BP by 24+3~(p<0.01) for 5h, increased HR at lh by 28+_~%(p<0.05) followed by a decrease, ~ d elevated CO by 41~5%(p
128LEUKOTRIENES ON PORCINE HEMODYNAMICS AND PROSTANOID RELEASE. V.B.Fiedler, M.Mardin, ~.J.Gardiner I, T.S.Abram I. Dept.'s Pharmacology, Bayer AG, Wuppertal, F.R.G., and Miles Lab., Slough, G.B. We studied the effects of i.c. leukotriene BA, Ca, D a and Ea(O.1-3 pg) on coronary blood flow and resistance in anesthetized pi~s. Conv6ntionaI hemodynamics were measured and the ECG was obtained in lead II. TxB 2 and 6-PGFl~were measured during LT effects on the heart. All LT's except LTB~ reduced coronary flow. Peak reduction was produced by 3 us of 9 9 ~ e,+ 0r+ 0r+ . , ~ each elcosanold: C,= 96+4,0 ; D,= 98+2,~ ; E,= 82+8,~ . Coronary reslstance increased by Oh= 65+18,~; C~= 22~+94A (p
1 2 9 ON THE D E L A Y E D A N T I I S C H A E M I C A C T I O N OF PgI 2 A N D ITS S T A B L E A N A L O G U E 7-oxo PgI 2. L. S z e k e r e s , ~ v a U d v a r y and A g n e s V~gh. D e p a r t m e n t of P h a r m a cology, U n i v e r s i t y M e d i c a l School, S z e g e d , H u n g a r y . We h a v e s h o w n that PgI 2 and its s t a b l e a n a l o g u e 7 - o x o P g I 2 - N a e x e r t s a late a n t i i s c h a e m i c e f f e c t in a d o g m o d e l of a n g i n a a p p e a r i n g 60-90 m i n a f t e r c o m p l e t i o n of i n f u s i o n w h e n b l o o d p r e s s u r e fall a n d i n h i b i t i o n of p l a t e l e t a g g r e g a t i o n w a s over. A m e ~ . b o l i c p r o t e c t i o n was f o u n d in rats p r e t r e a t e d w i t h 7 - o x o P g I 2 - N a 2 h o u r - b e f o r e e x c i s i n g the h e a r t and i n c u b a t i n g it for 1 m i n u t e in R i n g e r s o l u t i o n . T h e p r o t e c t i v e e f f e c t was also p r e s e n t in e x p e r i m e n t a l m y o c a r d i a l i n f a r c t i o n in c o n s c i o u s rats p r e t r e a ted 2 h o u r s b e f o r e o c c l u s i o n . H o w e v e r t r e a t m e n t d i d not i n c r e a s e s u r v i v a l rate and f a i l e d to r e d u c e the i n c i d e n c e and s e v e r i t y of a r r h y t h m i a s . Prol o n g e d t r e a t m e n t of dogs w i t h 7 - o x o P g I 2 - N a /250 u g / k g i.m. for 3 days/ m o d e r a t e d c h a n g e s i n d u c e d b y l i g a t i o n of the left a n t e r i o r d e s c e n d i n g cor o n a r y a r t e r y for 25 m i n u t e s , in the a n i m a l a n a e s t h e t i z e d and t h o r a c o t o m i z e d on the f o u r t h day. It r e d u c e d S T - s e g m e n t e l e v a t i o n , and i m p r o v e d b l o o d s u p p l y to the i s c h a e m i c area. D e s p i t e this m a n i f e s t a n t i i s c h a e m i c a c t i o n the i n c i d e n c e of p o s t - o c c l u s i o n a r r h y t h m i a s i n c r e a s e d . The incid e n c e of r e p e r f u s i o n a r r h y t h m i a s and t h a t of v e n t r i c u l a r f i b r i l l a t i o n w a s h o w e v e r s i g n i f i c a n t l y r e d u c e d as c o m p a r e d w i t h the n o n - t r e a t e d controls.