- Email: [email protected]
Diminution of injury reperfused ischemic myocardium by phenothiazines
J Mol Cell Cardiol 19 (Supplement Ill) (1987)
2 6 5 DIMINUTION OF INJURY REPERFUSED ISCHEMIC MYOCARDIUM BY PHENOTHIAZINES. J. Slezak, N. T r i b u l o v a , I. G a b a u e r , A. Z i e g e l h B f f e r , V. Holec, J. Slezak, Jr., I n s t i t u t e of E x p e r i m e n t a l Surgery, C e n t e r of P h y s i o l o gical Sciences, S l o v a k A c a d e m y of S c i e n c e s , B r a t i s l a v a , Czechoslovakia. The effect of c a l m o d u l i n i n h i b i t i o n by p h e n o t h i a z i n e s - Chlorprom a z i n e (CPR) and T r i f l u o p e r a z i n e (TFP) /Smith Kline and F r e n c h / on rep e r f u s i o n injury o% i s c h e m i c m y o c a r d i u m was studied. Left d e s c e n d i n g c o r o n a r y a. l i g a t i o n was p e r f o r m e d on 70 dogs d i v i d e d into four groups. I . g r o u p - p e r m a n e n t o c c l u s i o n (60, 120 and 180 min), I I . g r o u p - 60 min o c c l u s i o n and 120 min r e p e r f u s i o n , I I I . g r o u p - 60 min o c c l u s i o n , 15 mg/kg b.w. CPR, r e p e r f u s i o n 120 min, I V . g r o u p - 60 min o c c l u s i o n , 2 mg/kg b.w. TFP, 120 min r e p e r f u s i o n . CPR or TFP were admin i s t e r e d 30 min after the l i g a t i o n . Effect of drugs was s t u d i e d from histopathological, ultrastructural, physiological and b i o c h e m i c a l points of view and q u a n t i f i e d on t e t r a z o l i u m s t a i n e d gross s e c t i o n s . R e s u l t s reveal that t r e a t m e n t of a n i m a l s with p h e n o t h i a z i n e s having c a l m o d u l i n i n h i b i t o r y action, c o n s i d e r a b l y i m p r o v e d the u l t r a s t r u c t u r e of m y o c y t e s in area at risk and a l l o w e d for r e c o v e r y at least 60 per cent of injured m y o c y t e s after r e s t o r a t i o n of reflow. H i s t o c h e m i c a l and u l t r a s t r u c t u r a l f i n d i n g s t i g h t l y c o r r e l a t e with p h y s i o l o g i c a l and b i o c h e m i c a l results.
266
REDUCED TOLERANCE FOR GLOBAL ISCHEMIA AND REPERFUSION IN HYPERTROPHIED HEARTS OF AORTA-BANDED RATS. L.H. Snoeckx, G.J. van der Vusse, W.A. Cou~ans and R.S. Reneman. Department of Physiology, University of Limburg, Maastricht, The Netherlands. Isolated rat hearts were subjected to 45 min global ischemia ten weeks after aortabanding. Recovery was present in only 4 out of 9 hypertrophied (HT) hearts resulting in 15% restoration of aortic flow (vs 75% in control hearts). The HT hearts had a significantly lower coronary flow per gram heart weight and lost higher amounts of lactate dehydrogenase (LDH) than control hearts (28.6 vs 18.6 U.g--ww). Both groups lost comparable amounts of degradation products of adenine nueleotides (AN), but the release was significantly retarded in ~T hearts. After 45 min reperfusion tissue contents of degradation products of AN were comparable in both groups of hearts. Significantly higher contents of ATP (8.7 #mol.g-- dw) and ATP + ADP + AMP (14 #mol.g -I dw) wer~ found in controls than in the non-recovered HT hearts (resp. 5.7 and 10.3 #mol.g- dw). In ~he recovered HT hearts however, higher contents were found (resp. 7.3 and 12 mol.g- dw). Energy charge at the end of the reperfuslon period was significantly higher in control (0.79) and recovered HT hearts (0.77) than in non-recovered HT hearts (0.71). It is concluded that the higher loss of LDH indicates a more pronounced damage of myocardial structures. In the reperfused HT hearts the delayed washout of AN and the lower post-ischemic flow suggest incomplete recovery of tissue circulation and, hence, aggravation of ischemic damage (supported by MEDIGON/ZWO).
267 INCREASEDPLASMAFIBRONECTIN,VONWILLEBRAND FACTORANTIGEN (VIII:RAG) AND APOLIPOPROTEIN B LEVELS IN TYPE 2 DIABETIC PATIENTS WITH ISCHAEMIC HEART DISEASE ( I . H . D . ) . S.B.Solerte , M.Fioravanti Department of Internal Medicine,Medical C l i n i c I I , University of P a v i a , P a v i a , l t a l i a . Endothelial cell damage and blood l i p i d modifications might have a role in the pathogenesis of I.H.D. Twenty-six Type 2 diabetic patients with I.H.D. and 28 matched Type 2 diabetics without I.H.D. were studied. I.H.D. patients had poor metabolic control(HbA1c=9.3~2%,serum fructosamine=3.39+O.3 mmol/l)in comparison with patients without I.H.D.(8+1%,p
S.89
2 6 5 DIMINUTION OF INJURY REPERFUSED ISCHEMIC MYOCARDIUM BY PHENOTHIAZINES. J. Slezak, N. T r i b u l o v a , I. G a b a u e r , A. Z i e g e l h B f f e r , V. Holec, J. Slezak, Jr., I n s t i t u t e of E x p e r i m e n t a l Surgery, C e n t e r of P h y s i o l o gical Sciences, S l o v a k A c a d e m y of S c i e n c e s , B r a t i s l a v a , Czechoslovakia. The effect of c a l m o d u l i n i n h i b i t i o n by p h e n o t h i a z i n e s - Chlorprom a z i n e (CPR) and T r i f l u o p e r a z i n e (TFP) /Smith Kline and F r e n c h / on rep e r f u s i o n injury o% i s c h e m i c m y o c a r d i u m was studied. Left d e s c e n d i n g c o r o n a r y a. l i g a t i o n was p e r f o r m e d on 70 dogs d i v i d e d into four groups. I . g r o u p - p e r m a n e n t o c c l u s i o n (60, 120 and 180 min), I I . g r o u p - 60 min o c c l u s i o n and 120 min r e p e r f u s i o n , I I I . g r o u p - 60 min o c c l u s i o n , 15 mg/kg b.w. CPR, r e p e r f u s i o n 120 min, I V . g r o u p - 60 min o c c l u s i o n , 2 mg/kg b.w. TFP, 120 min r e p e r f u s i o n . CPR or TFP were admin i s t e r e d 30 min after the l i g a t i o n . Effect of drugs was s t u d i e d from histopathological, ultrastructural, physiological and b i o c h e m i c a l points of view and q u a n t i f i e d on t e t r a z o l i u m s t a i n e d gross s e c t i o n s . R e s u l t s reveal that t r e a t m e n t of a n i m a l s with p h e n o t h i a z i n e s having c a l m o d u l i n i n h i b i t o r y action, c o n s i d e r a b l y i m p r o v e d the u l t r a s t r u c t u r e of m y o c y t e s in area at risk and a l l o w e d for r e c o v e r y at least 60 per cent of injured m y o c y t e s after r e s t o r a t i o n of reflow. H i s t o c h e m i c a l and u l t r a s t r u c t u r a l f i n d i n g s t i g h t l y c o r r e l a t e with p h y s i o l o g i c a l and b i o c h e m i c a l results.
266
REDUCED TOLERANCE FOR GLOBAL ISCHEMIA AND REPERFUSION IN HYPERTROPHIED HEARTS OF AORTA-BANDED RATS. L.H. Snoeckx, G.J. van der Vusse, W.A. Cou~ans and R.S. Reneman. Department of Physiology, University of Limburg, Maastricht, The Netherlands. Isolated rat hearts were subjected to 45 min global ischemia ten weeks after aortabanding. Recovery was present in only 4 out of 9 hypertrophied (HT) hearts resulting in 15% restoration of aortic flow (vs 75% in control hearts). The HT hearts had a significantly lower coronary flow per gram heart weight and lost higher amounts of lactate dehydrogenase (LDH) than control hearts (28.6 vs 18.6 U.g--ww). Both groups lost comparable amounts of degradation products of adenine nueleotides (AN), but the release was significantly retarded in ~T hearts. After 45 min reperfusion tissue contents of degradation products of AN were comparable in both groups of hearts. Significantly higher contents of ATP (8.7 #mol.g-- dw) and ATP + ADP + AMP (14 #mol.g -I dw) wer~ found in controls than in the non-recovered HT hearts (resp. 5.7 and 10.3 #mol.g- dw). In ~he recovered HT hearts however, higher contents were found (resp. 7.3 and 12 mol.g- dw). Energy charge at the end of the reperfuslon period was significantly higher in control (0.79) and recovered HT hearts (0.77) than in non-recovered HT hearts (0.71). It is concluded that the higher loss of LDH indicates a more pronounced damage of myocardial structures. In the reperfused HT hearts the delayed washout of AN and the lower post-ischemic flow suggest incomplete recovery of tissue circulation and, hence, aggravation of ischemic damage (supported by MEDIGON/ZWO).
267 INCREASEDPLASMAFIBRONECTIN,VONWILLEBRAND FACTORANTIGEN (VIII:RAG) AND APOLIPOPROTEIN B LEVELS IN TYPE 2 DIABETIC PATIENTS WITH ISCHAEMIC HEART DISEASE ( I . H . D . ) . S.B.Solerte , M.Fioravanti Department of Internal Medicine,Medical C l i n i c I I , University of P a v i a , P a v i a , l t a l i a . Endothelial cell damage and blood l i p i d modifications might have a role in the pathogenesis of I.H.D. Twenty-six Type 2 diabetic patients with I.H.D. and 28 matched Type 2 diabetics without I.H.D. were studied. I.H.D. patients had poor metabolic control(HbA1c=9.3~2%,serum fructosamine=3.39+O.3 mmol/l)in comparison with patients without I.H.D.(8+1%,p
S.89