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Increase of lipoxygenase metabolites of arachidonic acid in canine myocardium by coronary occlusion and reperfusion
j Mol Cell Cardiol 19 (Supplement I) (1987) 5 8 T H E EFFECT OF COENZYME Q10 DERIVATIVES ON REPERFUSION ARRHYTHMIAS. T. Takamura, A. Fukushima ~, T. Kondo ~, M. Ajioka ~, S. Sugiyama, T. Ozawa. Departments of Biomedical Chemistry and Internal Medicine% Faculty of Medicine, University of Nagoya, Nagoya, Japan The effects of coenzyme Q10 (CoQ10) derivatives, carboxyl derivative of CoQ10 with benzoquinone type (BQ), and methylphenol type (MP), on reperfusion arrhythmias were investigated. Anesthetized dogs were divided into 3 groups: the control group (n=38), BQ group (n=ll), and MP group (n=ll). Physiological saline or 5 mg/kg of BQ or MP was premedicated in each group. Twenty min after the premedication, LAD was occluded for 15 min followed by 5 min reperfusion. Thirty-two percent of the control developed reperfusion arrhythmias, while none of the dogs pretreated with CoQ10 derivatives developed reperfusion arrhythmias. Immediately after 5 min of reperfusion, heart microsomes were prepared from the normal and reperfused areas and phospholipase (PLase) activity in microsomes was measured by high performance liquid chromatography. In the arrhythmias cases of the control group, PLase activity obtained from the reperfused area increased significantly compared with that from the normal area. In the non-arrhythmias cases of the control group and in both the C6QI0 derivatives group, PLsse activity from the reperfused area did not change significantly compared with that from the normal area in these groups. From these results, it is concluded that CoQ10 derivatives supress reperfusion arrhythmias by inhibition of PLase.
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L E U K O T R I E N E A N T A G O N I S T (ONO-I078) R E D U C E D I S C H E M I C M Y O C A R D I A L INJURY IN A CANINE O C C L U S I O N - R E P E R F U S I O N MODEL. Y. Toki, T. Ito, N. Hieda, T. Torii, H. Hashimoto, K.
Ogawa, and T. Satake. The 2nd Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan. In order to evaluate the influence of leukotriene antagonist on myocardial ischemic injury, effects of ON0-I078, which is a newly synthesized agent antagonizing predominantly leukotriene C 4 (LTC 4) and D 4 (LTD4) , were investigated in a canine occlusion-reperfusion model. In pentobarbital anesthetized open-chest dogs, the proximal left anterior descending coronary artery was occluded for 120 minutes and then reperfused for 300 minutes. Thirty minutes before occlusion animals were randomly assigned to either a treated group receiving continuous intravenous infusion of ONO-I078 1 ~g/kg/min or a control group receiving continuous intravenous infusion of the vehicle. Infarct size and risk area were determined by a dual staining technique using triphenyltetrazolium chloride and Evans' blue. 0N0-I078 reduced the extent of irreversible myocardial ischemic injury, when results were expressed as percent of risk region infarcted. This finding suggests that LTC 4 play an important role in the genesis of myocardial ischemic injury.
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INCREASE OF L I P O X Y G E N A S E METABOLITES OF A R A C H I D O N I C A C I D IN C A N ~ E MYOCARDIUM BY C O R O N A R Y OCCLUSION AND REPERFUSION. H i r o t a k a A k a g a m i "~, Nobuhiko Shibata 1].~nd Hideyuki Sanma 2~ The C e n t e r ~ Q r A d u l t D i s e a s e s Osaka, O s a k a J a p a n I~ a n d Eisai Co., Ltd., T o k y o J a p a n Z ~ B a s e d on o u r f i n d i n g that ischemic myocardium (IM) w a s d i s s o l v e d after infiltration of l e u k o c y t e s , it was s t u d i e d w h e t h e r any s u b s t a n c e having leukocyte chemoattractant a c t i v i t y was p r o d u c e d in IM or not. IM w a s p r o d u c e d by l i g a t i o n of c i r c u m f l e x b r a n c h of 1 - c o r o n a r y a r t e r y and in some cases the IM w a s r e p e r f u s e d by r e l e a s i n g c o r o n a r y ligation. In analysis of the IM by HPLC, it was found that 12and 5hydroxyeicosatetraenoic a c i d s (HETE) of l i p o x y g e n a s e metabolites of arachidonic acid (AA) i n c r e a s e d p r i o r to i n f i l t r a t i o n of l e u k o c y t e s in the myocardium subjected to i s c h e m i a l a s t i n g m o r e t h a n 6 h o u r s o r to r e p e r f u s i o n a f t e r i s c h e m i a l a s t i n g m o r e than 3 hours. T h e s e HETEs w e r e capable of w o r k i n g as n e u t r o p h i l chemoattractant. T h e i n c r e a s e of 12H E T E was c o n c l u d e d to be p r o d u c e d from not o n l y i n f i l t r a t e d leukocytes and/or platel~ts in IM, but also from ischemic myocytes inducing i n c r e a s e of Ca z+, b e c a u s e cultured cardiomyocytes p r o d u c e d 12- a n d 5H E T E in i n c u b a t i o n w i t h c a l c i u m i o n o p h o r e a n d / o r A A and the e x t r a c t of i n c u b a t i o n m e d i u m p r o m o t e d m i g r a t i o n of l e u c o c y t e s . S.42
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L E U K O T R I E N E A N T A G O N I S T (ONO-I078) R E D U C E D I S C H E M I C M Y O C A R D I A L INJURY IN A CANINE O C C L U S I O N - R E P E R F U S I O N MODEL. Y. Toki, T. Ito, N. Hieda, T. Torii, H. Hashimoto, K.
Ogawa, and T. Satake. The 2nd Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan. In order to evaluate the influence of leukotriene antagonist on myocardial ischemic injury, effects of ON0-I078, which is a newly synthesized agent antagonizing predominantly leukotriene C 4 (LTC 4) and D 4 (LTD4) , were investigated in a canine occlusion-reperfusion model. In pentobarbital anesthetized open-chest dogs, the proximal left anterior descending coronary artery was occluded for 120 minutes and then reperfused for 300 minutes. Thirty minutes before occlusion animals were randomly assigned to either a treated group receiving continuous intravenous infusion of ONO-I078 1 ~g/kg/min or a control group receiving continuous intravenous infusion of the vehicle. Infarct size and risk area were determined by a dual staining technique using triphenyltetrazolium chloride and Evans' blue. 0N0-I078 reduced the extent of irreversible myocardial ischemic injury, when results were expressed as percent of risk region infarcted. This finding suggests that LTC 4 play an important role in the genesis of myocardial ischemic injury.
60
INCREASE OF L I P O X Y G E N A S E METABOLITES OF A R A C H I D O N I C A C I D IN C A N ~ E MYOCARDIUM BY C O R O N A R Y OCCLUSION AND REPERFUSION. H i r o t a k a A k a g a m i "~, Nobuhiko Shibata 1].~nd Hideyuki Sanma 2~ The C e n t e r ~ Q r A d u l t D i s e a s e s Osaka, O s a k a J a p a n I~ a n d Eisai Co., Ltd., T o k y o J a p a n Z ~ B a s e d on o u r f i n d i n g that ischemic myocardium (IM) w a s d i s s o l v e d after infiltration of l e u k o c y t e s , it was s t u d i e d w h e t h e r any s u b s t a n c e having leukocyte chemoattractant a c t i v i t y was p r o d u c e d in IM or not. IM w a s p r o d u c e d by l i g a t i o n of c i r c u m f l e x b r a n c h of 1 - c o r o n a r y a r t e r y and in some cases the IM w a s r e p e r f u s e d by r e l e a s i n g c o r o n a r y ligation. In analysis of the IM by HPLC, it was found that 12and 5hydroxyeicosatetraenoic a c i d s (HETE) of l i p o x y g e n a s e metabolites of arachidonic acid (AA) i n c r e a s e d p r i o r to i n f i l t r a t i o n of l e u k o c y t e s in the myocardium subjected to i s c h e m i a l a s t i n g m o r e t h a n 6 h o u r s o r to r e p e r f u s i o n a f t e r i s c h e m i a l a s t i n g m o r e than 3 hours. T h e s e HETEs w e r e capable of w o r k i n g as n e u t r o p h i l chemoattractant. T h e i n c r e a s e of 12H E T E was c o n c l u d e d to be p r o d u c e d from not o n l y i n f i l t r a t e d leukocytes and/or platel~ts in IM, but also from ischemic myocytes inducing i n c r e a s e of Ca z+, b e c a u s e cultured cardiomyocytes p r o d u c e d 12- a n d 5H E T E in i n c u b a t i o n w i t h c a l c i u m i o n o p h o r e a n d / o r A A and the e x t r a c t of i n c u b a t i o n m e d i u m p r o m o t e d m i g r a t i o n of l e u c o c y t e s . S.42