Pyruvate is Superior to Glucose in Supporting Metabolism of Machine Perfused Donor Hearts for Transplantation

Introduction Heart transplantation is limited by the relatively brief ischemic tolerance of preserved myocardium that restricts optimal organ allocation. Experimental data suggest machine perfusion preservation of hearts for transplantation may be an effective strategy to extend the donor ischemic interval and utilize extended donor organs [1]. We have previously demonstrated that machine perfusion preserves graft oxidative metabolism and reduces myocardial injury as measured by CKMB release and apoptotic cell death even after a standard ischemic interval [2,3]. The preserved myocardium contains limited quantities of endogenous substrates and providing an exogenous fuel may be important to avoid myocardial substrate depletion. Conventional preservation solutions utilize glucose as a potential energy source but the value of glucose in supporting the energy demands of the machine perfused heart remain unclear. Other studies from our laboratory in small and large animal models using C and H magnetic resonance spectroscopy (MRS) demonstrated that glucose is a minor substrate of the machine perfused donor heart and that the lactate/alanine ratio is a discriminator of graft aerobic and anaerobic metabolism [3]. Additional data suggest that pyruvate becomes an increasingly important myocardial substrate during hypothermia [4]. In the current study we applied increasing concentrations of C glucose and pyruvate to the preservation solution of machine perfused rat hearts and measured incorporation of exogenous substrate into metabolic intermediates by H and C magnetic resonance spectroscopy. We hypothesized that pyruvate is a more effective substrate for supporting metabolism of the machine perfused donor heart thus preserving endogenous energy stores.