Reversal of ischemia-induced mitochondrial dysfunction after coronary reperfusion

This study was designed to clarify the mechanism of the reversal of ischemia-induced mitochondrial dysfunction after a reperfusion of the myocardium in dogs. The occlusion of the left anterior descending coronary artery for 30 min led to the significant increase of acyl-CoA level in ischemic mitochondria and the ischemic mitochondrial function was disturbed. Pre-infusion of 1 ml/kg of lipid before occlusion further increased the acyl-CoA accumulation in ischemic mitochondria, and concomitantly, the mitochondrial dysfunction was extended much more. On the other hand, 40 min of reperfusion following 30 min of occlusion diminished the accumulation of acyl-CoA in the reperfused mitochondria and restored the mitochondrial function. However, when lipid was pre-infused, acyl-CoA level in the reperfused mitochondria was still high and mitochondrial dysfunction was observed. Administration of carnitine prior to reperfusion not only suppressed the accumulation of acyl-CoA in the reperfused mitochondria but also preserved the mitochondrial function, despite the pre-infusion of lipid. There was a clear reciprocal correlation (r = ?0.97) between acyl-CoA level and mitochondrial function. These results suggest that acyl-CoA accumulation is one of the important factors in ischemia-induced mitochondrial dysfunction, and that reversal of the dysfunction after reperfusion is closely dependent upon the lowering of the acyl-CoA accumulation.