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Regional myocardial glucose uptake in rats of different ages. Effect of exercise
J Mol Cell Cardiol 19 (Supplement III) (1987)
142
REGIONAL MYOCARDIAL GLUCOSE UPTAKE IN RATS OF DIFFERENT AGES. EFFECT OF EXERCISE. J. Komulainen I , H. Kainulainen 2, T. Takala 3, V. Vihko 4. IDept. of Clin. Pathology, Kuopio Univ. Central Hospital, Kuopio, Finland;2Dept. of Clin. Sciences, Univ. of Tampere, Tampere, Finland;3Dept. of Sports Medicine, Deaconess Institute of 0ulu, 0ulu, Finland;4Research Institute for Physical Activity and Health, Jyv~skyl~, Finland. 3-5 months old male rats living in normal cage conditions exhibit a transmural left ventricular gradient of glucose uptake the subendocardial uptake being 30-40% higher than the subepicardial uptake. This gradient is shown in vitro (Langendorffperfusio~ aortic pressure 7.85 kPa) and in vivo. Female rats of same age express a less pronounced gradient (10-15%)o In old rats (22 or 27 months)the rate of glucose uptake is evenly distributed through the left ventricular wall. Swimming exercise abolishes the gradient in young male rats i_.nnvivo, as training (8-10 weeks) does in vitro. In female rats an opposite gradient, the epicardial uptake being high, is found after training. The gradient of left ventricular glucose uptake is similar to control two weeks after cessation of training. Training (20 weeks) does not affect myocardial glucose uptake of old rats. The total cardiac glucose uptake is known to correlate with mechanical work load. As the work load of subendocardium is greater than that of epicardium under basal conditions, it is suggested that distribution of work load also determines the regional distribution of cardiac glucose uptake. Present results may indicate, that physical exercise and ageing modulate the distribution of cardiac work load.
143
THE E ~ E C T S OF SULPHONYLUREAS ON THE DOG HF~RT AND RELATIONSHIP TO THEIR PHARMACOKINETIC ASPECTS. A. K~szeghy, G. Ballagi-Pord~z~y, ~.Z. Koltai, G. 2og~tsa. Research Department, National Institute of Cardiology, Budapest, Hungary. The availability of specific chemical assays and the development of appropriate biological models have made it feasible to study the relationship between the pharmacokinetics and the haemodynamic effects of hypoglycaemic sulphonylureas on the dog heart. The cardiovascular effects of tolbutamide and glipizide were studied on myocardial contractile force, cardiac output, mean arterial blood pressure and heart rate in 12 sulphonylurea treated and 6 control dogs. The data suggested that the dose-dependent changes noted were due to an alteration in cardiovascular dynamics after intravenous administration of tolbutamide /20-80-160 mg/kg/ and glipizide /0.2-0.5-1. O mg/kg/. The plasma concentration of tolbutamide was found strongly correlated with increase of myocardial contractility /r=0.9408 p ~ O . O 1 / , those of cardiac output /r=0,8666 pW-O. 05/, blood pressure /r=O. 9971 p < O. 001/ and with decrease of heart rate /r=-O. 9275 p~O. OO1/. Contrary of tolbutamide, glipizide reduce myocardial contractile force /r=-0.9833 p ~ O . 0 5 / and cardiac output /r=O~ p
144
I N H I B I T I O N OF C Y C L I C B L O O D F L O W A N D P R E S S U R E V A R I A T I O N S BY 7 - O X O - P G I 2. I. K r a s s 6 i , ~. U d v a r y , L. S z e k e r e s . D e p a r t m e n t of P h a r m a c o l o g y , University M e d i c a l School, S z e g e d , H u n g a r y . The e f f e c t of a s t a b l e P G I 2 - a n a l o g u e , 7-oxo-PGI2-Na was investigated on c y c l i c v a r i a t i o n s of c o r o n a r y b l o o d f l o w /CFV/ a n d p r e s s u r e /CPV/ in anaesthetized, thoracotomized dogs. C o r o n a r y b l o o d f l o w /CBF/ w a s m e a s u r e d in the d e s c e n d i n g b r a n c h of the l e f t a n t e r i o r c o r o n a r y a r t e r y /LAD/, p e r i p h e r a l c o r o n a r y p r e s s u r e /PCP/ in o n e of the side b r a n c h e s of the LAD. M o n o p o l a r epi- and e n d o c a r d i a l E C G s w e r e l e d f r o m the a r e a s u p p l i e d by the LAD. C F V a n d C P V w e r e i n d u c e d b y c o m b i n i n g the d i r e c t t r a u m a t i z a t i o n of the i n t e r n a l s u r f a c e of t h e L A D a n d a c r i t i c a l c o r o n a r y s t e n o sis by p l a c i n g a f i x e d c o n s t r i c t o r on the v e s s e l . A f t e r 1 h o u r o b s e r v a t i o n p e r i o d 7 - o x o - P G I 2 /iOO ug/kg/ w a s i n f u s e d i n t o the left a t r i u m . The d r u g r e d u c e d b l o o d p r e s s u r e , CBF a n d PCP and a b o l i s h e d C F V a n d C P V dur i n g i n f u s i o n and f o r f u r t h e r iO m i n . In some e x p e r i m e n t s a d e l a y e d eff e c t of the d r u g c o u l d be o b s e r v e d , t h a t is a f t e r r e a p p e a r a n c e of the c y c l i c a l t e r a t i o n s a s e c o n d p r o t e c t i v e a c t i o n a p p e a r e d . T h o u g h the d i m i n u t i o n of the f r e q u e n c y of c y c l i c v a r i a t i o n s w a s n o t s i g n i f i c a n t in this late p r o t e c t i v e phase, b u t e x t e n t of the c h a n g e s in C F V a n d C P V a n d the S T - s e g m e n t e l e v a t i o n in the e p i - a n d e n d o c a r d i a l E C G s w a s m a r k e d l y reduced.
S.48
142
REGIONAL MYOCARDIAL GLUCOSE UPTAKE IN RATS OF DIFFERENT AGES. EFFECT OF EXERCISE. J. Komulainen I , H. Kainulainen 2, T. Takala 3, V. Vihko 4. IDept. of Clin. Pathology, Kuopio Univ. Central Hospital, Kuopio, Finland;2Dept. of Clin. Sciences, Univ. of Tampere, Tampere, Finland;3Dept. of Sports Medicine, Deaconess Institute of 0ulu, 0ulu, Finland;4Research Institute for Physical Activity and Health, Jyv~skyl~, Finland. 3-5 months old male rats living in normal cage conditions exhibit a transmural left ventricular gradient of glucose uptake the subendocardial uptake being 30-40% higher than the subepicardial uptake. This gradient is shown in vitro (Langendorffperfusio~ aortic pressure 7.85 kPa) and in vivo. Female rats of same age express a less pronounced gradient (10-15%)o In old rats (22 or 27 months)the rate of glucose uptake is evenly distributed through the left ventricular wall. Swimming exercise abolishes the gradient in young male rats i_.nnvivo, as training (8-10 weeks) does in vitro. In female rats an opposite gradient, the epicardial uptake being high, is found after training. The gradient of left ventricular glucose uptake is similar to control two weeks after cessation of training. Training (20 weeks) does not affect myocardial glucose uptake of old rats. The total cardiac glucose uptake is known to correlate with mechanical work load. As the work load of subendocardium is greater than that of epicardium under basal conditions, it is suggested that distribution of work load also determines the regional distribution of cardiac glucose uptake. Present results may indicate, that physical exercise and ageing modulate the distribution of cardiac work load.
143
THE E ~ E C T S OF SULPHONYLUREAS ON THE DOG HF~RT AND RELATIONSHIP TO THEIR PHARMACOKINETIC ASPECTS. A. K~szeghy, G. Ballagi-Pord~z~y, ~.Z. Koltai, G. 2og~tsa. Research Department, National Institute of Cardiology, Budapest, Hungary. The availability of specific chemical assays and the development of appropriate biological models have made it feasible to study the relationship between the pharmacokinetics and the haemodynamic effects of hypoglycaemic sulphonylureas on the dog heart. The cardiovascular effects of tolbutamide and glipizide were studied on myocardial contractile force, cardiac output, mean arterial blood pressure and heart rate in 12 sulphonylurea treated and 6 control dogs. The data suggested that the dose-dependent changes noted were due to an alteration in cardiovascular dynamics after intravenous administration of tolbutamide /20-80-160 mg/kg/ and glipizide /0.2-0.5-1. O mg/kg/. The plasma concentration of tolbutamide was found strongly correlated with increase of myocardial contractility /r=0.9408 p ~ O . O 1 / , those of cardiac output /r=0,8666 pW-O. 05/, blood pressure /r=O. 9971 p < O. 001/ and with decrease of heart rate /r=-O. 9275 p~O. OO1/. Contrary of tolbutamide, glipizide reduce myocardial contractile force /r=-0.9833 p ~ O . 0 5 / and cardiac output /r=O~ p
144
I N H I B I T I O N OF C Y C L I C B L O O D F L O W A N D P R E S S U R E V A R I A T I O N S BY 7 - O X O - P G I 2. I. K r a s s 6 i , ~. U d v a r y , L. S z e k e r e s . D e p a r t m e n t of P h a r m a c o l o g y , University M e d i c a l School, S z e g e d , H u n g a r y . The e f f e c t of a s t a b l e P G I 2 - a n a l o g u e , 7-oxo-PGI2-Na was investigated on c y c l i c v a r i a t i o n s of c o r o n a r y b l o o d f l o w /CFV/ a n d p r e s s u r e /CPV/ in anaesthetized, thoracotomized dogs. C o r o n a r y b l o o d f l o w /CBF/ w a s m e a s u r e d in the d e s c e n d i n g b r a n c h of the l e f t a n t e r i o r c o r o n a r y a r t e r y /LAD/, p e r i p h e r a l c o r o n a r y p r e s s u r e /PCP/ in o n e of the side b r a n c h e s of the LAD. M o n o p o l a r epi- and e n d o c a r d i a l E C G s w e r e l e d f r o m the a r e a s u p p l i e d by the LAD. C F V a n d C P V w e r e i n d u c e d b y c o m b i n i n g the d i r e c t t r a u m a t i z a t i o n of the i n t e r n a l s u r f a c e of t h e L A D a n d a c r i t i c a l c o r o n a r y s t e n o sis by p l a c i n g a f i x e d c o n s t r i c t o r on the v e s s e l . A f t e r 1 h o u r o b s e r v a t i o n p e r i o d 7 - o x o - P G I 2 /iOO ug/kg/ w a s i n f u s e d i n t o the left a t r i u m . The d r u g r e d u c e d b l o o d p r e s s u r e , CBF a n d PCP and a b o l i s h e d C F V a n d C P V dur i n g i n f u s i o n and f o r f u r t h e r iO m i n . In some e x p e r i m e n t s a d e l a y e d eff e c t of the d r u g c o u l d be o b s e r v e d , t h a t is a f t e r r e a p p e a r a n c e of the c y c l i c a l t e r a t i o n s a s e c o n d p r o t e c t i v e a c t i o n a p p e a r e d . T h o u g h the d i m i n u t i o n of the f r e q u e n c y of c y c l i c v a r i a t i o n s w a s n o t s i g n i f i c a n t in this late p r o t e c t i v e phase, b u t e x t e n t of the c h a n g e s in C F V a n d C P V a n d the S T - s e g m e n t e l e v a t i o n in the e p i - a n d e n d o c a r d i a l E C G s w a s m a r k e d l y reduced.
S.48