Effects of afterload and heart rate on NAD(P)H redox state in the isolated rabbit heart.
NAD(P)H redox state was monitored using surface fluorescence in isolated, normothermic, working rabbit hearts under conditions of limited substrate (glucose alone) and abundant substrate (glucose + lactate). To alter work, afterload was varied between 75 and 150 cmH2O or heart rate was increased in steps until no further increase in myocardial oxygen consumption (MVO2) occurred. Alterations in afterload did not cause a significant change in NAD(P)H fluorescence. Progressive increases in heart rate did not alter NAD(P)H emission until MVO2 began to decline (approximately 300 beats/min), ventricular performance decompensated, and there was evidence of ischemia, at which time NAD(P)H fluorescence increased. Although the addition of 3 mM lactate to the perfusate resulted in a rapid increase in NAD(P)H fluorescence, NAD(P)H fluorescence still did not respond to altered workload. The results suggest that NAD(P)H redox state is not the primary stimulus for increased myocardial respiration secondary to tachycardia or afterload. However, despite increased rates of cardiac work, NAD(P)H was maintained at a relatively stable level, suggesting that reducing equivalent supply to the electron transport chain increases in parallel with increased MVO2.
Heineman
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FW
Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Balaban
R S
RS
D000818:Animals; D005453:Fluorescence; D006321:Heart / Q000502:physiology*; D006339:Heart Rate; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011817:Rabbits
D009249:NADP