Oxygen free radical producing leukocytes cause functional depression of isolated rat hearts: role of leukotrienes

Journal of Molecular and Cellular Cardiology
A G SembO D Mjøs

Abstract

Polymorphonuclear granulocytes PMN) are suggested mediators of myocardial ischemia-reperfusion injury. We have previously shown that activated PMN producing oxygen free radicals (OFR) in the coronary circulation are cardiodepressive. OFR may induce lipid peroxidation and production of eicosanoids. We have investigated the influence of cyclo-oxygenase and lipoxygenase inhibitors on the effects of activated, OFR producing PMN in the Langedorff rat heart model. Left ventricular developed pressure (LVDP) was measured by a balloon in the left ventricle. Human PMN and drugs were given into the aortic cannula for 10 min and the hearts were observed for 30 min thereafter. After infusion for 5 min OFR production in the cellular infusate was measured at the level of the aortic cannula by a chemiluminescence (CL) technique. Phorbol 12-myristate 13-acetate (PMA)-activated PMN (n = 8), produced a CL response of 27649 +/- 11048 counts (mean +/- S.E.M.), and reduced coronary flow (CF) to 53 +/- 6% (mean +/- S.E.M.) and LVDP to 38 +/- 9% of baseline values at the end of the observation period. Ibuprofen (n = 6), a cyclooxygenase (CO) inhibitor, neither influenced the CL response (31915 +/- 7563) of activated PMN, nor the reduction of CF and LV...Continue Reading

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