Differential sensitivity of rat cardiac sarcolemma and mitochondria to damage induced by lipid peroxidation

Abstract

It is well known that the sarcolemma is the organelle most susceptible to lipid peroxidative attack in the isolated membrane preparations. To determine whether this also occurs in the intact heart, we studied the effect of cumene hydroperoxide, an agent capable of initiating lipid peroxidation, on the ultrastructure and lanthanum (La) staining of isolated rat hearts perfused with HEPES buffer (pH 7.4) containing: 140 mM NaCl, 5 mM KCl, 1 mM MgCl2, 3 mM HEPES, 1.5 mM CaCl2 and 11 mM glucose. No ultrastructural alterations or intracellular deposits of La were observed in myocytes of rats perfused with HEPES buffer. Perfusion with cumene hydroperoxide (0.5 mM) for 30 min induced a release of malondialdehyde-like substance in the perfusate and a spectrum of myocardial ultrastructural alterations. La was always observed only outside the sarcolemma in myocytes with moderate damage consisting of clearing of the mitochondrial matrix and slight margination of chromatin in the nuclei. Intracellular La was found in myocytes with severe and irreversible damages consisting of fragmentation of cristae and electron-dense amorphous particles in mitochondria. La was deposited on the outer surface of the mitochondrial membranes, lipid droplets and myofilaments. These data suggest that mitochondria are more susceptible than is the sarcolemma to lipid peroxidation induced by cumene hydroperoxide in the beating rat heart.