Dynamics of energy metabolism in the transplanted human heart during reperfusion

Abstract

Reperfusion after ischemia of the heart generates further damage to the myocardium through a variety of mechanisms including free radical generation, calcium overload, and abnormalities of energetics. In this study, the uptake and release of metabolites involved in energy metabolism were investigated during 45 minutes of reperfusion of donor human heart after transplantation to evaluate the nature of the metabolic abnormalities and the time course of recovery. Analysis of coronary sinus and arterial blood samples in 11 transplant recipients showed the following: (1) In the first minute of reperfusion, lactate release was observed accompanied by an uptake of pyruvate, resulting in a markedly elevated lactate/pyruvate ratio. The pH value of coronary sinus blood was lower than that of arterial blood by 0.1 unit, inorganic phosphate was released, and a massive efflux of nucleotide catabolites was observed. Hemoglobin oxygen saturation of coronary sinus blood was almost equal to that of arterial blood, showing minimal myocardial oxygen extraction. Coronary flow was approximately 300 ml/min at reperfusion with minor changes in the first minute. (2) From the second minute onward, pyruvate was released for over 45 minutes, contrasting with the first minute of reperfusion. Lactate was significantly released for up to 10 minutes of reperfusion, but myocardial uptake of lactate was not restored by the end of the observation period. However, the lactate/pyruvate ratio in coronary sinus blood recovered at the onset of this phase. Both pH changes in coronary sinus blood and phosphate release were restored within 5 minutes, but release of nucleotide catabolites was still significant after 30 minutes of reperfusion. The oxygen saturation of hemoglobin in coronary sinus blood decreased gradually in a biphasic mode over the 45 minutes, indicating gradual restoration of myocardial oxygen uptake. Coronary flow measured for up to 10 minutes of reperfusion decreased to a minimal value of 200 ml/min in the third minute, followed by restoration of initial flow. These data highlight the profound alterations in energy metabolism that occur during reperfusion of the transplanted heart. These changes, which may result from the preceding ischemia and impaired oxidative metabolism at the onset of reperfusion, were partially reversed in the first minutes. However, impaired pyruvate and lactate use and underperfusion reflected by the release of purine catabolites persisted for a period of more than 30 minutes of reperfusion.