Ultrastructural, functional, and metabolic correlates in the ischemic rat heart. Effects of free fatty acid.

Abstract

A study correlating functional, metabolic, and ultrastructural changes in the ischemic myocardium was conducted on isolated working rat hearts, both in the presence and absence of fatty acid. Glucose alone (11 mM) or glucose plus palmitic acid (1.5 mM) were used as metabolic substrates. A 60-min period of whole-heart ischemia resulted in a more dramatic morphological alteration in those hearts receiving palmitate than in those receiving no palmitate. In ischemic hearts receiving palmitate, intramitochondrial amorphous densities of both rounded and elongated types were observed. These densities did not develop in hearts receiving glucose alone over the same period of ischemia. Such morphological alterations were associated with a more severe deterioration of mechanical function in the presence of palmitate. Biochemical determinations of fatty acid derivatives showed increased tissue levels of acyl esters of CoA and carnitine in ischemic hearts, but levels of long-chain acyl carnitine were much higher in those ischemic hearts receiving palmitate. Furthermore, from the data obtained on isolated mitochondria, it appeared that the mitochondrial level of long-chain acyl carnitine was approximately four times higher in the ischemic hearts receiving palmitate than in those receiving no palmitate. This great rise in mitochondrial levels of long-chain acyl carnitine correlated with modifications of the mitochondrial structure and with the appearance of amorphous densities.