On the mechanism of ischemia-induced mitochondrial dysfunction

This study was designed to clarify the mechanism of ischemia-induced mitochondrial dysfunction. Anesthetized 24 dogs were divided into 4 groups, which were premedicated with saline for the controls, lipid emulsion 1 ml/kg, DL-carnitine 300 mg/kg or DL-propionylcarnitine 100 mg/kg. Myocardial mitochondria were prepared from both ischemic and non-ischemic areas after 30 min of coronary ligation and their functions, the levels of acyl-CoA and free L-carnitine were measured. In the control group, acyl-CoA level in ischemic mitochondria increased significantly compared with that in non-ischemic mitochondria. Administration of lipid emulsion further increased acyl-CoA level in ischemic mitochondria, but premedication with carnitine or propionylcarnitine prevented the elevation of acyl-CoA level by increasing free L-carnitine level in mitochondria. Ischemic mitochondrial function was disturbed in the control group and premedication with lipid accelerated the dysfunction, while premedication with carnitine or propionylcarnitine reduced the dysfunction. There was a clear reciprocal correlation (r = -0.98) between acyl-CoA level and mitochondrial function. These results indicate that accumulation of acyl-CoA is one of the important factors in ischemia-induced mitochondrial dysfunction.