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Am J Physiol Heart Circ Physiol (May 20, 2005). doi:10.1152/ajpheart.00322.2005
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Submitted on March 31, 2005
Accepted on May 13, 2005

Pyruvate-fortified cardioplegia suppresses oxidative stress and enhances phosphorylation potential of arrested myocardium

E. Marty Knott1, Myoung-Gwi Ryou1, Jie Sun1, Abraham Heymann1, Arti B Sharma1, Yu Lei1, Mirza Baig2, Robert T Mallet1*, and Albert H Olivencia-Yurvati3

1 Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX, USA
2 Department of Pharmacy, Plaza Medical Center of Fort Worth, Fort Worth, TX, USA
3 Department of Surgery, University of North Texas Health Science Center, Fort Worth, TX, USA

* To whom correspondence should be addressed. E-mail: malletr{at}hsc.unt.edu.

Cardioplegic arrest for bypass surgery imposes global ischemia on the myocardium which generates oxyradicals and depletes myocardial high energy phosphates. The glycolytic metabolite pyruvate, but not its reduced congener lactate, increases phosphorylation potential and detoxifies oxyradicals in ischemic and post-ischemic myocardium. This study tested the hypothesis that pyruvate mitigates oxidative stress and preserves energy state in cardioplegically arrested myocardium. In situ swine hearts were arrested for 60 min with a 4:1 mixture of blood and crystalloid cardioplegia solution containing 188 mM glucose alone (control) or with additional 23.8 mM lactate or 23.8 mM pyruvate, then reperfused for 3 min with cardioplegia-free blood. Glutathione (GSH), glutathione disulfide (GSSG), and energy metabolites (phosphocreatine (PCr), creatine (Cr), inorganic phosphate (Pi) were measured in myocardium snap frozen at 45 min arrest and 3 min reperfusion to determine antioxidant GSH redox state (GSH/GSSG) and PCr phosphorylation potential ([PCr]/([Cr][Pi)])). Coronary sinus 8-isoprostane indexed oxidative stress. Pyruvate cardioplegia lowered 8-isoprostane release approximately 40% during arrest vs. control and lactate cardioplegia. Lactate and pyruvate cardioplegia dampened (P < 0.05 vs. control) the surge of 8-isoprostane release following reperfusion. Pyruvate doubled GSH/GSSG vs. lactate cardioplegia during arrest, but GSH/GSSG fell in all 3 groups following reperfusion. Myocardial [PCr]/([Cr][Pi)]) was maintained in all three groups during arrest. Pyruvate cardioplegia doubled [PCr]/([Cr][Pi)]) vs. control and lactate cardioplegia following reperfusion. Pyruvate cardioplegia mitigates oxidative stress during cardioplegic arrest and enhances myocardial energy state upon reperfusion.




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