Lipid Peroxidation and Acute Myocardial Ischemia
Lipid peroxides (LP) and free radicals (FR) have recently been identified by us as metabolic intermediates during acute myocardial ischemia. The mechanism of lipid peroxidation is not clearly understood. We hypothesize: 1) FR production increases during ischemia due to alteration in the redox state of the mitochondria and due to interaction between metabolites and O2; 2) FR foster increased formation of LP with a concomitant decrease in protective antioxidants such as glutathione peroxidase (GP) and ascorbic acid (ASC). To test this hypothesis, we first studied animal models, rat and dog. In the rat, 48 hrs post coronary occlusion (CO), the lipid peroxide content in the infarcted left ventricular tissue (LV) measured as its product malondialdehyde (MDA) increased from 0.31 to 0.58 nm/ mg P (p<.001), an increase of 87% while GP decreased from 62 to 21 nm/min/mg P (p<.001). Superoxide dismutase contents decreased from 81 to 63 µg/g (p<.001). The polyunsaturated fatty acid (PUFA) contents diminished significantly (arachidonic acid from 19 to 16%, p<.001). In the dog, sequential transcardiac changes in blood showed very early increase of both FR as studied by electron spin resonance spectrometry in lyophilized samples and catecholamines (norepinephrine, NE, and epinephrine, E).
KeywordsAscorbic Acid Lipid Peroxide Electron Spin Resonance Glutathione Peroxidase Coronary Sinus
Unable to display preview. Download preview PDF.
- 1.YAMAMOTO, H. Studies on clinical applications of electron spin resonance (ESR) spectrometry: Application to diagnosis of ischemic heart disease. Japan. Circ. J. 35, 1257–1258 (1971).Google Scholar
- 2.AKIYAMA, K. Studies on myocardial metabolism in the ischemic heart. Part II. Studies by the method of electron spin resonance. Japan. Circ. J. 33, 146–147 (1969).Google Scholar
- 4.HALL, E.T. The oxygen effect, in: Radiobiology for the radiologist. p. 48, New York, Harper and Row 1973).Google Scholar
- 6.TAPPEL, A. Free radical lipid peroxidation and its inhibition by vitamin E and selenium. Federation Proc. 24, 73–78 (1965).Google Scholar
- 18.LOANN, W., SREIBER, J., & GULICH, W. On the possible involvement of ascorbic acid and copper proteins in leukemia. IV. ESR investigations on the interaction between ascorbic acid and some copper proteins. Z. Naturforsch. 34, 550–554 (1979).Google Scholar
- 19.WLAAS, E., LOVSTAD, R., & WALAAS, O. Free radical formation of catecholamines by the action of ceruloplasmin. Proc. Biochem. Soc. J92, 18P–19P (1964).Google Scholar
- 22.HARMON, D., & PIETTE, L. Free radical theory of aging. Free radical reactions in serum. J. Gerontol. 21(4), 560–565 (1966).Google Scholar
- 27.RAO, P.S., & MUELLER, H.S. Lipid peroxide production and glutathione peroxidase depletion in rat myocardium after acute infarction. Clin. Chem. 27, 1027 (1981).Google Scholar
- 28.RAO, P.S., RAO, P.B., BROCK, R.E., & MUELLER, H.S. Patterns of free radicals across the heart during acute myocardial infarct. Clin. Res. 28, 758A (1980).Google Scholar
- 29.RAO, P.S., EVANS, R.G., & MUELLER, H.S. Sequential transcardiac changes in free radicals, catecholamines and lipid peroxides in early experimental myocardial infarction. Clin. Res. 30, 214A (1982).Google Scholar
- 31.MCCOY, P.B., GIBSON, D.D., FONG, K., & Hornbrook, K.R. Effect of glutathione peroxidase on lipid peroxidation in biological membranes. Biochem. Biophys. Acta 431, 459–468 (1976).Google Scholar
- 32.JAAKKOLA, K. Administration of vitamin E along with selenium to patients with ischemic heart disease. Prevention, 33(9), 97 (1981).Google Scholar