Pyruvate/dichloroacetate supply during reperfusion accelerates recovery of cardiac energetics and improves mechanical function following cardioplegic arrest

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Abstract
Objectives: Cardioplegic arrest during cardiac surgery induces severe abnormalities of the pyruvate metabolism, which may affect functional recovery of the heart. We aimed to evaluate the effect of pyruvate and dichloroacetate administration during reperfusion on recovery of mechanical function and energy metabolism in the heart subjected to prolonged cardioplegic arrest. Methods: Four groups of rat hearts perfused in working mode were subjected to cardioplegic arrest (St. Thomas’ No. 1), 4 h of ischaemia at 8°C and reperfusion with either Krebs buffer alone (C) or with 2.8 mM pyruvate (P), with 1 mM dichloroacetate (D), or with a combination of both (PD). Mechanical function was recorded before cardioplegic arrest and at the end of experiments. In groups C and PD, additional experiments were performed using 31P nuclear magnetic resonance spectroscopy in non-working Langendorff mode to evaluate cardiac high-energy phosphate concentration changes throughout the experiment. Results: Improved recovery of cardiac output (% of the preischaemic value±SEM, n=9–12) was observed in all three treated groups (65.7±4.3, 59.5±5.2 and 59.5±5.3% in PD, P and D, respectively) as compared with C (42.2±4.6%; P≪0.05). Recovery of coronary flow was improved from 66.4±3.8 in C to 94.9±8.6% in PD (P≪0.05). The phosphocreatine recovery rate in the first minutes of reperfusion was increased from 9.9±1.5 in C to 31.5±4.3 μmol/min per g dry wt in PD (P≪0.001). No differences were observed in ATP or phosphocreatine concentrations at the end of experiment. Conclusions: The administration of pyruvate and dichloroacetate improves the recovery of mechanical function following hypothermic ischaemia. Accelerated restoration of the energy equilibrium in the initial phase of reperfusion may underlie the metabolic mechanism of this effect.