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

Seema Mital, MD^*, Kit E. Loke, PhD, Linda J. Addonizio, MD^*, Mehmet C. Oz, MD^* and Thomas H. Hintze, PhD

^* Department of Pediatrics, Divisions of Pediatric Cardiology and Cardiothoracic Surgery, Columbia University College of Physicians and Surgeons, New York, New York, USA
Department of Physiology, New York Medical College, Valhalla, New York, USA

View larger version (17K): [in a new window]   Figure 1 Bradykinin, enalaprilat and amlodipine caused a dose-dependent reduction in myocardial oxygen consumption in failing human hearts. Left ventricular assist device HF group (solid circles) showed a greater reduction in oxygen consumption compared with the control HF group (open circles). *p < 0.05 from baseline; #p < 0.05 from HF. HF = heart failure; LVAD = left ventricular assist device; MVO2 = myocardial oxygen consumption.

View larger version (19K): [in a new window]   Figure 2 (A) Diltiazem and (B) nitroglycerin caused dose-dependent reductions in MVO2 in failing human hearts. There was no difference in the response of the LVAD (solid circles) and HF (open circles) groups to diltiazem or nitroglycerin. *p < 0.05 from baseline. HF = heart failure; LVAD = left ventricular assist device; MVO2 = myocardial oxygen consumption.

View larger version (43K): [in a new window]   Figure 3 (A) The effect of L-NAME, inhibitor of nitric oxide synthesis, on MVO2 at the highest doses of drug in the LVAD group is shown. Nw-nitro-L-arginine methyl ester attenuated the effect of bradykinin, enalaprilat and amlodipine on oxygen consumption. Nw-nitro-L-arginine methyl ester had no effect on decrease in oxygen consumption in response to diltiazem and nitroglycerin. Striped bar = LVAD-HF; solid bar = +L-NAME. #p < 0.05 from control. (B) Effect of succinate on myocardial oxygen consumption. Succinate, NAD-independent substrate of the electron transport chain, increased MVO2 in both HF and LVAD-HF groups, and this response was not different between the two groups. Amlo = amlodipine; BK = bradykinin; Dilt = diltiazem; Enal = enalaprilat; HF = heart failure; L-NAME = Nw-nitro-L-arginine methyl ester; LVAD = left ventricular assist device; MVO2 = myocardial oxygen consumption; NTG = nitroglycerin.