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Protective effect of piridoxilate on hypoxic heart
32 R e s u l t s show that h e a r t cells r e a c h i n g c o n f l u e n c y at day-3 in c u l t u r e s y n t h e s i z e s e v e r a l p o l y ( A ) - m R N A species. A m o n g t h e m is a c o n s p i c u o u s peak of poly(A)m R N A which, f r o m its w e l l - d e f i n e d l o c a t i o n b e t w e e n 18S and 28S r i b o s o m a l RNA, can be i d e n t i f i e d as the m e s s e n g e r RNA for the h e a v y c h a i n of cardiac myosin.
52.
A L T E R A T I O N S OF THE P O S T A N O X I C R E C O V E R Y OF THE I N T R A C E L L U L A R R E D O X STATE AS O B S E R V E D IN E A R L Y STAGES OF RAT HEART H Y P E R T R O P H Y . J. Moravec, M. Laplace, G. Renault, U n i t ~ de R e c h e r c h e s de P a t h o l o g i e C a r d i o v a s c u l a i r e , I N S E R M U2, H6pital L ~ o n Bernard, 94450 L i m e i l - B r ~ v a n n e s , France. The c a p a c i t y of i s o l a t e d p e r f u s e d h e a r t s (Langendorff preparation) to o x i d i z e an e x c e s s of N A D H has b e e n t e s t e d by m e a n s of s u r f a c e f l u o r i m e t r y (365 and 470 nm). The k i n e t i c s of the state 5 - t o - s t a t e 3 t r a n s i t i o n has b e e n m o n i t o r e d 2 or 8 days after the b a n d i n g of the aorta and the r e s u l t s c o m p a r e d w i t h those o b t a i n e d on h e a l t h y p r e p a r a t i o n s . The m o s t imp o r t a n t d a t a are the following: (i) the a m p l i t u d e of the signal (PdN r e d u c t i o n ) , as o b s e r v e d 1 min of the anoxic p e r f u s i o n , is c o m p a r a b l e in all groups examined. It equals to 186, 185 and 170% of the a e r o b i c steady state signal in controls, 2 days and 8 daysl a s t i n g stenoses; (2) the time n e c e s s a r y to reach n o r m o x i c r e d o x c o n d i t i o n s is 38.5, 28.5 and 59.25 sec in the three groups e x a m i n e d ; (3) the c o r r e s p o n d i n g m a x i m a l rates of the r e o x i d a t i o n (% of a n o x i c signal/sec) are the following: 3.71, 6.58 and 2.81 per cent/sec. T h e s e r e s u l t s s u g g e s t there is, in h y p e r t r o p h i e d m y o c a r d i u m , a t r a n s i e n t p e r i o d of i m p r o v e d r e s p i r a tory activity, f o l l o w e d by an i m p a i r m e n t of m i t o c h o n d r i a l function. The s i g n i f i c a n c e of the above d a t a for the e t i o l o g y of c o n t r a c t i l e failure w i l l be discussed.
53.
P R O T E C T I V E E F F E C T OF P I R I D O X I L A T E ON H Y P O X I C HEART. P.R. Moret, U. Lutzen, C a r d i a c M e t a b o l i s m L a b o r a t o r y , C e n t e r of C a r d i o l o g y , Geneva, Switzerland. The p r o t e c t i v e a c t i o n of p i r i d o x i l a t e was s t u d i e d on rat's h e a r t in acute d e e p h y p o x i a (isolated h e a r t p e r f u s e d - L a n g e n d o r f f t e c h n i q u e - d u r i n g one hour
33 w i t h n o n - o x y g e n a t e d f l u i d w i t h glucose, pO 2 ~ 25 m m Hg) and in p r o l o n g e d m i l d h y p o x i a (3-days s t a y at an a l t i t u d e of 3500 m, pa02: ~ 55 m m Hg). M y o c a r d i a l b i o p s i e s w e r e t a k e n at the end of the p e r f u s i o n in acute d e e p h y p o x i a and at the end of the stay in p r o l o n g e d m i l d h y p o x i a and a n a l y s e d for CP, ATP and l a c t a t e (L). In e x p e r i m e n t s on a c u t e hypoxia, w i t h p i r i d o x i l a t e a d d e d to the p e r f u s i o n liquid, ATP c o n t e n t was h i g h e r as C o m p a r e d to c o n t r o l g r o u p without p i r i d o x i l a t e (p<0.001) and L c o n t e n t m u c h lower (p<0.001). In p r o l o n g e d h y p o x i a , p i r i d o x i l a t e a l o n e g i v e n o r a l l y has little effect, but w h e n a s s o c i a t e d w i t h p r o p r a n o l o l , CP and ATP c o n t e n t s are h i g h e r (p<0.001) and L lower (p<0.001) as c o m p a r e d w i t h the c o n t r o l group. P i r i d o x i l a t e has no e f f e c t on the m y o c a r d i a l m e t a b o l i s m of n o r m a l l y o x y g e n a t e d heart. On h y p o x i c heart, h e a r t rate and c o r o n a r y f l o w do not change. The m e c h a n i s m s of a c t i o n of p i r i d o x i l a t e w i l l be d i s c u s s e d . Our r e s u l t s show that u n d e r certain c i r c u m s t a n c e s p i r i d o x i l a t e can p r o t e c t the h e a r t a g a i n s t some of the d e l e t e r i o u s e f f e c t s of hypoxia.
54.
E F F E C T OF E X O G E N O U S L A C T A T E ON THE M Y O C A R D I A L FUNCTION DURING NON-NUTRIENT CIRCULATION. M. Nagano, M. K a w a m u r a , D e p a r t m e n t of I n t e r n a l M e d i cine, J i k e i U n i v e r s i t y , S c h o o l of M e d i c i n e , Tokyo, Japan. The c o n t r a c t i l e m e c h a n i s m in the h e a r t is d e p e n d e n t u p o n an a d e q u a t e store of m y o c a r d i a l h i g h e n e r gy p h o s p h a t e s . The i s o l a t e d rat h e a r t from h e a r t lung p r e p a r a t i o n c a n n o t g e n e r a t e s u f f i c i e n t e n e r g y in the a b s e n c e of o x i d i z a b l e s u b s t r a t e s in the circ u l a t e d blood. G l u c o s e has b e e n k n o w n as an i m p o r tant s u b s t r a t e for e n e r g y p r o d u c t i o n and to i m p r o v e a c t i v e l y the d i m i n i s h e d p e r f o r m a n c e w h i c h d e v e l o p e d d u r i n g n o n - n u t r i e n t medium. In this report, e x p e r i m e n t s are p e r f o r m e d to d e t e r m i n e the e f f e c t of lactate, a d d e d 30 m i n a f t e r n o n - n u t r i e n t c i r c u l a t i o n on the f u n c t i o n and e n e r g y m e t a b o l i s m of the rat h e a r t w h i c h is i s o l a t e d by h e a r t lung p r e p a r a t i o n , c i r c u lated w i t h a r t i f i c i a l blood, c o m p o s e d of rat red cells in PVP, e l e c t r o l y t e s and n o n - n u t r i e n t solution. The r e s u l t s i n d i c a t e that there is no e f f e c t of exog e n o u s l a c t a t e on the m y o c a r d i a l f u n c t i o n and e n e r g y m e t a b o l i s m . The rat h e a r t c i r c u l a t e d w i t h l a c t a t e
52.
A L T E R A T I O N S OF THE P O S T A N O X I C R E C O V E R Y OF THE I N T R A C E L L U L A R R E D O X STATE AS O B S E R V E D IN E A R L Y STAGES OF RAT HEART H Y P E R T R O P H Y . J. Moravec, M. Laplace, G. Renault, U n i t ~ de R e c h e r c h e s de P a t h o l o g i e C a r d i o v a s c u l a i r e , I N S E R M U2, H6pital L ~ o n Bernard, 94450 L i m e i l - B r ~ v a n n e s , France. The c a p a c i t y of i s o l a t e d p e r f u s e d h e a r t s (Langendorff preparation) to o x i d i z e an e x c e s s of N A D H has b e e n t e s t e d by m e a n s of s u r f a c e f l u o r i m e t r y (365 and 470 nm). The k i n e t i c s of the state 5 - t o - s t a t e 3 t r a n s i t i o n has b e e n m o n i t o r e d 2 or 8 days after the b a n d i n g of the aorta and the r e s u l t s c o m p a r e d w i t h those o b t a i n e d on h e a l t h y p r e p a r a t i o n s . The m o s t imp o r t a n t d a t a are the following: (i) the a m p l i t u d e of the signal (PdN r e d u c t i o n ) , as o b s e r v e d 1 min of the anoxic p e r f u s i o n , is c o m p a r a b l e in all groups examined. It equals to 186, 185 and 170% of the a e r o b i c steady state signal in controls, 2 days and 8 daysl a s t i n g stenoses; (2) the time n e c e s s a r y to reach n o r m o x i c r e d o x c o n d i t i o n s is 38.5, 28.5 and 59.25 sec in the three groups e x a m i n e d ; (3) the c o r r e s p o n d i n g m a x i m a l rates of the r e o x i d a t i o n (% of a n o x i c signal/sec) are the following: 3.71, 6.58 and 2.81 per cent/sec. T h e s e r e s u l t s s u g g e s t there is, in h y p e r t r o p h i e d m y o c a r d i u m , a t r a n s i e n t p e r i o d of i m p r o v e d r e s p i r a tory activity, f o l l o w e d by an i m p a i r m e n t of m i t o c h o n d r i a l function. The s i g n i f i c a n c e of the above d a t a for the e t i o l o g y of c o n t r a c t i l e failure w i l l be discussed.
53.
P R O T E C T I V E E F F E C T OF P I R I D O X I L A T E ON H Y P O X I C HEART. P.R. Moret, U. Lutzen, C a r d i a c M e t a b o l i s m L a b o r a t o r y , C e n t e r of C a r d i o l o g y , Geneva, Switzerland. The p r o t e c t i v e a c t i o n of p i r i d o x i l a t e was s t u d i e d on rat's h e a r t in acute d e e p h y p o x i a (isolated h e a r t p e r f u s e d - L a n g e n d o r f f t e c h n i q u e - d u r i n g one hour
33 w i t h n o n - o x y g e n a t e d f l u i d w i t h glucose, pO 2 ~ 25 m m Hg) and in p r o l o n g e d m i l d h y p o x i a (3-days s t a y at an a l t i t u d e of 3500 m, pa02: ~ 55 m m Hg). M y o c a r d i a l b i o p s i e s w e r e t a k e n at the end of the p e r f u s i o n in acute d e e p h y p o x i a and at the end of the stay in p r o l o n g e d m i l d h y p o x i a and a n a l y s e d for CP, ATP and l a c t a t e (L). In e x p e r i m e n t s on a c u t e hypoxia, w i t h p i r i d o x i l a t e a d d e d to the p e r f u s i o n liquid, ATP c o n t e n t was h i g h e r as C o m p a r e d to c o n t r o l g r o u p without p i r i d o x i l a t e (p<0.001) and L c o n t e n t m u c h lower (p<0.001). In p r o l o n g e d h y p o x i a , p i r i d o x i l a t e a l o n e g i v e n o r a l l y has little effect, but w h e n a s s o c i a t e d w i t h p r o p r a n o l o l , CP and ATP c o n t e n t s are h i g h e r (p<0.001) and L lower (p<0.001) as c o m p a r e d w i t h the c o n t r o l group. P i r i d o x i l a t e has no e f f e c t on the m y o c a r d i a l m e t a b o l i s m of n o r m a l l y o x y g e n a t e d heart. On h y p o x i c heart, h e a r t rate and c o r o n a r y f l o w do not change. The m e c h a n i s m s of a c t i o n of p i r i d o x i l a t e w i l l be d i s c u s s e d . Our r e s u l t s show that u n d e r certain c i r c u m s t a n c e s p i r i d o x i l a t e can p r o t e c t the h e a r t a g a i n s t some of the d e l e t e r i o u s e f f e c t s of hypoxia.
54.
E F F E C T OF E X O G E N O U S L A C T A T E ON THE M Y O C A R D I A L FUNCTION DURING NON-NUTRIENT CIRCULATION. M. Nagano, M. K a w a m u r a , D e p a r t m e n t of I n t e r n a l M e d i cine, J i k e i U n i v e r s i t y , S c h o o l of M e d i c i n e , Tokyo, Japan. The c o n t r a c t i l e m e c h a n i s m in the h e a r t is d e p e n d e n t u p o n an a d e q u a t e store of m y o c a r d i a l h i g h e n e r gy p h o s p h a t e s . The i s o l a t e d rat h e a r t from h e a r t lung p r e p a r a t i o n c a n n o t g e n e r a t e s u f f i c i e n t e n e r g y in the a b s e n c e of o x i d i z a b l e s u b s t r a t e s in the circ u l a t e d blood. G l u c o s e has b e e n k n o w n as an i m p o r tant s u b s t r a t e for e n e r g y p r o d u c t i o n and to i m p r o v e a c t i v e l y the d i m i n i s h e d p e r f o r m a n c e w h i c h d e v e l o p e d d u r i n g n o n - n u t r i e n t medium. In this report, e x p e r i m e n t s are p e r f o r m e d to d e t e r m i n e the e f f e c t of lactate, a d d e d 30 m i n a f t e r n o n - n u t r i e n t c i r c u l a t i o n on the f u n c t i o n and e n e r g y m e t a b o l i s m of the rat h e a r t w h i c h is i s o l a t e d by h e a r t lung p r e p a r a t i o n , c i r c u lated w i t h a r t i f i c i a l blood, c o m p o s e d of rat red cells in PVP, e l e c t r o l y t e s and n o n - n u t r i e n t solution. The r e s u l t s i n d i c a t e that there is no e f f e c t of exog e n o u s l a c t a t e on the m y o c a r d i a l f u n c t i o n and e n e r g y m e t a b o l i s m . The rat h e a r t c i r c u l a t e d w i t h l a c t a t e