Left ventricular assist device implantation augments nitric oxide dependent control of mitochondrial respiration in failing human hearts

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Abstract

OBJECTIVES: The objective of the study was to evaluate nitric oxide (NO) mediated regulation of mitochondrial respiration after implantation of a mechanical assist device in end-stage heart failure. BACKGROUND: Ventricular unloading using a left ventricular assist device (LVAD) can improve mitochondrial function in end-stage heart failure. Nitric oxide modulates the activity of the mitochondrial electron transport chain to regulate myocardial oxygen consumption (MVO2). METHODS: Myocardial oxygen consumption was measured polarographically using a Clark-type oxygen electrode in isolated left ventricular myocardium from 26 explanted failing human hearts obtained at the time of heart transplantation. RESULTS: The rate of decrease in oxygen concentration was expressed as a percentage of baseline. Results of the highest dose of drug are shown. Decrease in MVO2was greater in LVAD hearts (n = 8) compared with heart failure controls (n = 18) in response to the following drugs: bradykinin (-34 ± 3% vs. -24 ± 5%), enalaprilat (-37 ± 5% vs. -23 ± 5%) and amlodipine (-43 ± 13% vs. -16 ± 5%; p < 0.05 from controls). The decrease in MVO2in LVAD hearts was not significantly different from controls in response to diltiazem (-22 ± 5% in both groups) and exogenous NO donor, nitroglycerin (-33 ± 7% vs. -30 ± 3%). N(W)-nitro-L-arginine methyl ester, inhibitor of NO synthase, attenuated the response to bradykinin, enalaprilat and amlodipine. Reductions in MVO2in response to diltiazem and nitroglycerin were not altered by inhibiting NO. CONCLUSIONS: Chronic LVAD support potentiates endogenous NO-mediated regulation of mitochondrial respiration. Use of medical or surgical interventions that augment NO bioavailability may promote myocardial recovery in end-stage heart failure. (C) 2000 by the American College of Cardiology.

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APA

Mital, S., Loke, K. E., Addonizio, L. J., Oz, M. C., & Hintze, T. H. (2000). Left ventricular assist device implantation augments nitric oxide dependent control of mitochondrial respiration in failing human hearts. Journal of the American College of Cardiology, 36(6), 1897–1902. https://doi.org/10.1016/S0735-1097(00)00948-7

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