17-BETA-ESTRADIOL REDUCES CARDIAC LEUKOCYTE ACCUMULATION IN MYOCARDIAL-ISCHEMIA REPERFUSION INJURY IN RAT

We investigated whether oestrogens modulate the phenomenon of leukocyt e accumulation during ischaemia and reperfusion of the myocardium. Ana esthetized rats were subjected to total occlusion (1 h) of the left ma in coronary artery followed by 1 h reperfusion. Sham myocardial ischae mia-reperfusion rats (Sham) were used as controls. Myocardial necrosis , myocardial myeloperoxidase activity, serum creatinine phosphokinase activity, serum and macrophages tumour necrosis factor (TNF-alpha) and the myocardial staining of intercellular adhesion molecule-1 (ICAM-1) were evaluated. Myocardial ischaemia plus reperfusion in untreated ra ts produced marked myocardial necrosis, increased serum creatinine pho sphokinase activity (348 +/- 38 U/ml) and cardiac myeloperoxidase acti vity, a marker of polymorphonuclear leukocyte accumulation, both in th e area at risk and in the necrotic area (MPO 9 +/- 1.1 mU/g tissue and 8.2 +/- 1 mU/g tissue, respectively), and induced a marked increase i n the macrophage (156 +/- 14 U/ml at the end of reperfusion) and serum (344 +/- 12 U/ml, at the end of reperfusion) levels of TNF-alpha. Fin ally, myocardial ischaemia-reperfusion injury increased ICAM-1 stainin g in the myocardium. Administration of 17 beta-oestradiol (5, 10 and 2 0 mu g/kg, i.m. 5 min after induction of myocardial ischaemia-reperfus ion injury), lowered myocardial necrosis and myeloperoxidase activity in the area at risk and in the necrotic area, reduced serum and macrop hages TNF-alpha (20 +/- 3 U/ml and 9 +/- 3 U/ml, respectively) and dec reased serum creatinine phosphokinase activity (67 +/- 3 U/ml). Oestro gen treatment also blunted the increased staining of ICAM-1 in the inj ured myocardium. Finally, 17 beta-oestradiol added in vitro to periton eal macrophages collected from untreated rats subjected to myocardial ischaemia-reperfusion injury, significantly reduced TNF-alpha producti on. Our results suggest that 17 beta-oestradiol, by inhibiting TNF-alp ha production, limits the deleterious ICAM-1-mediated binding of leuko cytes to injured mycardium and protects against myocardial isthaemia-r eperfusion injury. (C) 1997 Elsevier Science B.V.