Studies on cumene hydroperoxide-induced lipid peroxidation in the isolated perfused rat heart.
In the isolated, perfused rat heart, lipid peroxidation, induced by cumene hydroperoxide (Cum OOH), is accompanied by the release of malondialdehyde (MDA). Using a modified perfusion technique resulting in the separate collection of coronary and interstitial effluent, it can be shown that upon Cum OOH (0.5 mM) perfusion there is an immediate release of MDA in the coronary effluent and a delayed release in the interstitial fluid, indicating the susceptibility and coronary vascular tissue towards free radical-induced lipid peroxidation. Perfusion with Cum OOH leads to an initial increase of the coronary flow and a depressed contractility followed by a cardiac arrest concomitantly with the onset of MDA release in the interstitial fluid. Finally, during prolonged perfusion the coronary flow diminishes and contracture of the heart muscle ('stone heart') develops. These phenomena resemble those occurring during the 'calcium paradox'. Although the contractility diminishes immediately after the perfusion with Cum OOH the tissue ATP level and energy charge (formula; see text) remain constant. From the moment of cardiac arrest the ATP and creatine phosphate levels gradually decrease and the energy charge drops simultaneously with the appearance of MDA in the interstitial fluid. In contrast to the calcium paradox there is no simultaneous increase in the myocardial AMP level. Various mitochondrial enzymes (cytochrome c oxidase, monoamine oxidase, carnitinepalmitoyltransferase I and palmitoyl CoA synthetase) were tested and not affected by Cum OOH perfusion. During the development of contracture after 20 min of Cum OOH perfusion massive contraction band necrosis of cardiac tissue occurs. However, overall protein release is lower when compared with the protein release during the calcium paradox.(ABSTRACT TRUNCATED AT 250 WORDS)
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity*; D002118:Calcium / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008929:Mitochondria, Heart / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats
D000227:Adenine Nucleotides; D001555:Benzene Derivatives; D005609:Free Radicals; D008054:Lipid Peroxides; D010725:Phosphocreatine; D008315:Malondialdehyde; C007164:cumene hydroperoxide; D002118:Calcium