Cytochrome c release: A mitochondrial predictor of post-ischemic cardiac graft recovery in donation after circulatory death

Abstract

Objectives: In cardiac ischemia-reperfusion, mitochondrial damage is determinant in cellular survival. Ischemia-reperfusion injury is a major concern for graft quality in heart transplantation with donation after circulatory death (DCD). Therefore, we investigated whether release of cytochrome c by cardiac mitochondria could be used as an early biomarker of hemodynamic recovery in an isolated rat heart model of DCD. Methodology: Isolated working rat hearts underwent 21, 24, 27, 30, or 33 min warm, global ischemia followed by 60 min reperfusion. Left ventricular work (developed pressure-heart rate product) was monitored with an intraventricular pressure catheter. Coronary effluent was collected at 10 minutes of reperfusion for measurement of cytochrome c and lactate using commercially available kits. Results: Compared with non-ischemic controls, cytochrome c release was 2-fold higher after 21 min ischemia and increased progressively with ischemic duration to reaching a 10-fold elevation after 33 min ischemia. Cytochrome c and lactate release inversely correlated with post-ischemic left ventricular work (r=-0.81, p<0.001 and r=-0.46, p<0.01, respectively). Conclusion: Cytochrome c is a sensitive, early predictor of cardiac hemodynamic recovery that can be measured easily and rapidly. Cytochrome c could be useful for evaluation of DCD cardiac grafts for transplantation in addition to the currently used lactate.