Metabolic modulation of cellular redox potential can improve cardiac recovery from ischemia-reperfusion injury.
OBJECTIVE
Ischemia-reperfusion heart injury is an important pathologic condition against which many strategies, mainly involving antioxidants or radical scavengers, have been developed, but without satisfactory results. In the present experiment, modulation of the cytosolic NADH/NAD ratio by pyruvate and aspartate was tested in order to protect the heart from ischemia-reperfusion injury.


METHODS
Effects of pyruvate and aspartate on cardiac function recovery and redox potential were analyzed in the isolated heart of male Sprague-Dawley rats. Hearts were made globally ischemic for 20 min and then reperfused for 30 min.


RESULTS
Pyruvate and aspartate protected against tissue injury and improved contractile function after reperfusion of ischemic hearts, and these substances effectively decreased the tissue and cytosolic NADH/NAD ratio of the myocardium in a dose-dependent manner. Postischemic cardiac functions were negatively related to tissue and cytosolic NADH/NAD ratios. Increased NADH selectively inhibited myocardial xanthine dehydrogenase in vitro. It was thus expected that a decrease of NADH might limit the production of reactive oxygen species through the recovery of xanthine dehydrogenase activity.


CONCLUSIONS
These results indicate that a decrease of NADH is related to pyruvate and aspartate-induced protection of ischemic myocardium.
Department of Pharmacology, Heart Research Institute, Seoul National University College of Medicine, Republic of Korea.
J W
JW
Park
Y S
YS
Chun
M S
MS
Kim
Y C
YC
Park
S J
SJ
Kwak
S C
SC
Park
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D019289:Pyruvic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014970:Xanthines / Q000378:metabolism
D014970:Xanthines; D009243:NAD; D001224:Aspartic Acid; D019289:Pyruvic Acid