INTERLEUKIN 1-ALPHA-INDUCED EXPRESSION OF MANGANOUS SUPEROXIDE-DISMUTASE REDUCES MYOCARDIAL REPERFUSION INJURY IN THE RAT

We investigated the effects of pretreatment with interleukin(IL)-1 alp ha on the expression of manganous (Mn) superoxide dismutase (SOD) mRNA and reperfusion-induced arrhythmias and the size of myocardial infarc t in rats, Male Wistar rats received 10 mg intraperitoneal injections of human recombinant IL-1 alpha. Their hearts were thereafter isolated at 6, 12, 24, 36 h. A Northern analysis showed that Mn-SOD mRNA was m ainly expressed in the heart and slightly in kidney, but not in any ot her organs. The expression of Mn-SOD mRNA peaked at 6 h after the inje ction of IL-1 alpha. The Mn-SOD protein content was most increased 12 h after injection, In the isolated heart model, the rats were pretreat ed with IL-1 alpha 24 h earlier and their hearts were perfused by the Langendorff method, After 20 min of ischemia which was induced by a li gation of a coronary artery, reperfusion-induced arrhythmias were obse rved. There were no significant differences in the incidence of ventri cular arrhythmias between the IL-1 alpha pretreated and the untreated hearts, IL-1 alpha pretreatment significantly reduced the mean duratio n of the ventricular arrhythmias and also delayed the onset of arrhyth mias. The effect of IL-1 alpha pretreatment was also investigated in a 30-min model of ischemia followed by a 3-min reperfusion in anestheti zed rats, The infarct size expressed as a percentage of the area at ri sk was significantly reduced in the IL-1 alpha pretreated hearts compa red with the untreated hearts. The left ventricular systolic pressure increased significantly in rat hearts pretreated with IL-1 alpha. Our results therefore showed that the pretreatment with IL-1 alpha induced the overexpression of Mn-SOD mRNA in the rat hearts and also suggeste d that pretreatment with IL-1 alpha 24 h before ischemia reduced the r isk of ischemia-reperfusion injury. (C) 1995 Academic Press Limited