Pyruvate mitigates oxidative stress during reperfusion of cardioplegia-arrested myocardium.
BACKGROUND
Cardioplegic arrest and reperfusion of the myocardium imposes oxidative stress that could potentially inactivate metabolic enzymes and compromise energy production. This study determined the impact of cardioplegic arrest and reperfusion on activities of several oxidant-sensitive enzymes, and tested whether pyruvate, a natural metabolic fuel and antioxidant, mitigates oxidant stress, protects enzymes, and bolsters myocardial energy state after reperfusion.


METHODS
In situ swine hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, and then reperfused for 3 minutes with cardioplegia-free blood with or without approximately 12 mM pyruvate. Tissue metabolites and enzyme activities were measured in left ventricular myocardium snap frozen at 45 minutes of arrest and 3 minutes of reperfusion.


RESULTS
The 8-isoprostane content, a measure of lipid peroxidation, sharply increased upon reperfusion, coincident with a 70% decline in redox state of the intracellular antioxidant glutathione. Aconitase and glucose 6-phosphate dehydrogenase activities fell during arrest; creatine kinase and phosphofructokinase were inactivated upon reperfusion. Pyruvate suppressed 8-isoprostane formation, maintained glutathione redox state, and enhanced phosphocreatine phosphorylation potential, a measure of myocardial energy state, during reperfusion. Pyruvate reactivated creatine kinase and aconitase, which are at least partially mitochondrial enzymes, but did not protect the cytosolic enzymes glucose 6-phosphate dehydrogenase and phosphofructokinase.


CONCLUSIONS
Administration of pyruvate upon reperfusion after cardioplegic arrest mitigates oxidative stress, protects mitochondrial enzymes and increases myocardial energy state. These results support therapeutic application of pyruvate-enhanced reperfusion to prevent cardiac injury after cardioplegic arrest.
Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas 76107-2699, USA.
E Marty
EM
Knott
Jie
J
Sun
Yu
Y
Lei
Myoung-Gwi
MG
Ryou
Albert H
AH
Olivencia-Yurvati
Robert T
RT
Mallet
D000818:Animals; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced / Q000379:methods*; D023421:Models, Animal; D009206:Myocardium; D018384:Oxidative Stress / Q000187:drug effects*; D019289:Pyruvic Acid / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine
D019289:Pyruvic Acid