- Email: [email protected]
Pathogenesis of diabetic cardiomyopathy
j Mol Cell Cardiol 19 (Supplement III) (1987)
52
EFFECTS OF D I L T I A Z E M ON EARLY ISCHEMIC V E N T R I C U L A R A R R H Y T H M I A S SC Dennis, WA Coetzee, B Keding, LH Opie, MRC Heart Research Unit, University of q~pe Town, Observatory, South Africa. H Y P O T H E S I S : Ca ~- channel antagonists inhibit ischemic arrhythmias by a specific electrophysiologic effect rather than by indirect antiischemic effects. DATA: We examined the influence of d i l t i a z e m on the time to v e n t r i c u l a r tachycardia (VT) in an u n d e r p e r f u s e d guinea pig heart preparation, in which prompt contractile failure, severe fixed low flow ischemia and ventricular pacing e l i m i n a t e d the potential for any a n t i - i s c h e m i c effects. Tissue m e t a b o l i t e s and purine release were unaltered by diltiazem. Flow (ml/min/g wet wt) 0.25 0.17 0.17 C O N C L U S I O N :
ventricular restricted,
53
Pacing frequency 6Hz 4Hz 6Hz
Time Control 35+5 ~ ) 36T2 (12) 20T2 (ii)
to VT (min) +diltiazem(luM) 40+7 (7) 50~5 (ii) 31~3 (ii)
NS (p<0.05) (p<0.01)
The direct e l e c t r o p h y s i o l o g i c a l actions of diltiazem on arrhythmias are only of importance when flow is severely e s p e c i a l l y at higher pacing frequencies.
G L Y C O L Y T I C FLUX IN ISCHEMIA: EFFECTS OF B U F F E R I N G AND pH SC Dennis, S Legalatladi, LH Opie, MRC Heart Research Unit, University of Cape Town, Observatory, South Africa. HYPOTHESIS: Proton efflux promotes lactate release from ischemic hearts. DATA: Isolated rat hearts were perfused at pH 7.0-7.4 with i0, 15, or 25mM HCO~-:5% CO^ K r e b s - H e n s e l e i t buffers and s u b j e c t e ~ 4 t o 9 z . . 5 30min of low (5%) f~ow ischemla in the presence of 2-[ HI and U-[~ C] glucose. The effects of increased buffering and pH on the release of lactate and on the energy p r o d u c t i o n from the glycolytic m e t a b o l i s m of 2-[3H] glucose (2 ATP/mol) and the oxidative decarboxylation of U[14C] glucose (36 ATP/mol) is shown below. !HCO3_ ~] 10mM,pH7.0 15mMtpH7.2 25mM.oH3.4 (n) u m o l / 3 0 m i n / g wet wt Lactate efflux (8) 10.5+1.7 18.5+1.7 26.0+4.2 Glycolytic ATP (8) 9.8T1.2 17.8~2.8 27.4~4.4 Oxidative ATP (5) 8.6~2.2 5.8~2.0 ii.2~0.7 CONCLUSION: Increased buffering concentration and pH accelerates lactate efflux and enhances the glycolytic ATP production capacity (p<0.005) of the u n d e r p e r f u s e d myocardium.
54
PATHOGENESIS 0P DIABETIC CARDI0}~YOPATHY. N.S. Dhalla. Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
S.18
52
EFFECTS OF D I L T I A Z E M ON EARLY ISCHEMIC V E N T R I C U L A R A R R H Y T H M I A S SC Dennis, WA Coetzee, B Keding, LH Opie, MRC Heart Research Unit, University of q~pe Town, Observatory, South Africa. H Y P O T H E S I S : Ca ~- channel antagonists inhibit ischemic arrhythmias by a specific electrophysiologic effect rather than by indirect antiischemic effects. DATA: We examined the influence of d i l t i a z e m on the time to v e n t r i c u l a r tachycardia (VT) in an u n d e r p e r f u s e d guinea pig heart preparation, in which prompt contractile failure, severe fixed low flow ischemia and ventricular pacing e l i m i n a t e d the potential for any a n t i - i s c h e m i c effects. Tissue m e t a b o l i t e s and purine release were unaltered by diltiazem. Flow (ml/min/g wet wt) 0.25 0.17 0.17 C O N C L U S I O N :
ventricular restricted,
53
Pacing frequency 6Hz 4Hz 6Hz
Time Control 35+5 ~ ) 36T2 (12) 20T2 (ii)
to VT (min) +diltiazem(luM) 40+7 (7) 50~5 (ii) 31~3 (ii)
NS (p<0.05) (p<0.01)
The direct e l e c t r o p h y s i o l o g i c a l actions of diltiazem on arrhythmias are only of importance when flow is severely e s p e c i a l l y at higher pacing frequencies.
G L Y C O L Y T I C FLUX IN ISCHEMIA: EFFECTS OF B U F F E R I N G AND pH SC Dennis, S Legalatladi, LH Opie, MRC Heart Research Unit, University of Cape Town, Observatory, South Africa. HYPOTHESIS: Proton efflux promotes lactate release from ischemic hearts. DATA: Isolated rat hearts were perfused at pH 7.0-7.4 with i0, 15, or 25mM HCO~-:5% CO^ K r e b s - H e n s e l e i t buffers and s u b j e c t e ~ 4 t o 9 z . . 5 30min of low (5%) f~ow ischemla in the presence of 2-[ HI and U-[~ C] glucose. The effects of increased buffering and pH on the release of lactate and on the energy p r o d u c t i o n from the glycolytic m e t a b o l i s m of 2-[3H] glucose (2 ATP/mol) and the oxidative decarboxylation of U[14C] glucose (36 ATP/mol) is shown below. !HCO3_ ~] 10mM,pH7.0 15mMtpH7.2 25mM.oH3.4 (n) u m o l / 3 0 m i n / g wet wt Lactate efflux (8) 10.5+1.7 18.5+1.7 26.0+4.2 Glycolytic ATP (8) 9.8T1.2 17.8~2.8 27.4~4.4 Oxidative ATP (5) 8.6~2.2 5.8~2.0 ii.2~0.7 CONCLUSION: Increased buffering concentration and pH accelerates lactate efflux and enhances the glycolytic ATP production capacity (p<0.005) of the u n d e r p e r f u s e d myocardium.
54
PATHOGENESIS 0P DIABETIC CARDI0}~YOPATHY. N.S. Dhalla. Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
S.18