Metabolic products and myocardial ischemia

Metabolic products accumulate in ischemic myocardium secondary to reduced coronary flow, which prevents adequate washout of vascular spaces, and to reduced oxidative metabolism. The most notable products that accumulate are NADH, H+, lactate, CO2, long-chain acyl-CoA, and long-chain acyl carnitine. These products interfere with the production of ATP and the functioning of the myocardium. Glycolytic production of ATP is inhibited by accumulation of NADH, H+, and lactate. Mitochondrial and plasma membrane function may be altered by the acyl esters of CoA and carnitine. Mitochondrial membranes become structurally distorted and fragmented, and lipid-containing amorphous densities appear in the matrix. Structural alterations of mitochondria occur more frequently in hearts receiving high concentrations of fatty acids and correlate with high tissue levels of acyl esters of CoA and carnitine. Addition of acyl carnitine to mitochondria isolated from normal hearts results in nodulose-appearing cristae and fragmentation of mitochondrial membranes.