Pyruvate/dichloroacetate supply during reperfusion accelerates recovery ofcardiac energetics and improves mechanical function following cardioplegicarrest

Objectives: Cardioplegic arrest during cardiac surgery induces severe abnor malities of the pyruvate metabolism, which may affect functional recovery o f the heart. We aimed to evaluate the effect of pyruvate and dichloroacetat e 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 degreesC and reperfusion with either Krebs buffer alone (C) or with 2.8 mM pyruvate (P), with 1 mM dichloroacecate (D), or with a combination of both (PD). Mec hanical function was recorded before cardioplegic arrest and at the end of experiments. In groups C and PD, additional experiments were performed usin g; P-31 nuclear magnetic resonance spectroscopy in non-working Langendorff mode to evaluate cardiac high-energy phosphate concentration changes throug hout the experiment. Results: Improved recovery of cardiac output (% of the preischaemic value +/- SEM, n = 9-12) was observed in all three treated gr oups (65.7 +/- 4.3, 59.5 +/- 5.2 and 59.5 +/- 5.3% in PD, P and D, respecti vely) as compared with C (42.2 +/- 4.6%; P < 0.05). Recovery of coronary fl ow 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 i ncreased from 9.9 +/- 1.5 in C to 31.5 +/- 4.3 mu mol/min per g dry wt in P D (P < 0.001). No differences were observed in ATP or phosphocreatine conce ntrations at the end of experiment. Conclusions: The administration of pyru vate and dichloroacetate improves the recovery of mechanical function follo wing hypothermic ischaemia. Accelerated restoration of the energy equilibri um in the initial phase of reperfusion map underlie the metabolic mechanism of this effect. (C) 2001 Elsevier Science B.V. All rights reserved.