Left ventricular assist device implantation augments nitric oxide dependent control of mitochondrial respiration in failing human hearts.
OBJECTIVE
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 MVO2 was 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 MVO2 in 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 MVO2 in 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.
Mital
S
S
Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Loke
K E
KE
Addonizio
L J
LJ
Oz
M C
MC
Hintze
T H
TH
D000293:Adolescent; D000328:Adult; D005260:Female; D006333:Heart Failure / Q000503:physiopathology* / Q000628:therapy; D006353:Heart-Assist Devices; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D010101:Oxygen Consumption
D009569:Nitric Oxide