Basic Research in Cardiology Basic Res Cardio187:385-392 (1992) Ibuprofen abolishes the increase in leucocyte chemilmninescence observed during ischemic myocardial failure, but fails to improve hemodynamic function K. Ytrehus, A.-G. Semb, and E. S. P. Myhre Institute of Medical Biology, University of Tromsr Tromsr Norway Summary: The aim of the study was to evaluate 1) whether the ability of leucocytes to produce oxygen radicals was increased by ischemia and 2) if ibuprofen pretreatment could influence leucocyte oxygen radical production, hemodynamic function, and myocardial oxygen consumption during acute ischemic myocardial failure. We studied two groups of anesthetized dogs (control and ibuprofen-treated), both subjected to coronary embolization with polystyrene microspheres (diameter 50 ~tm). The embolization procedure was ended when left-ventricular end-diastolic pressure in both groups exceeded 20 mm Hg. Before and after induction of ischemia leucocytes were isolated and stimulated with opsonized zymosan, and oxygen radical production was measured using the luminol-dependent chemiluminescence tech- nique. Significant increase occurred in oxygen radical production (from 10.9 _+ 2.2 to 16.3 • 2.3 - 105 counts - 10 ~ cells-~ - 60 rain -I) 90 rain after failure in the control group, whereas in ibuprofen-pretreated dogs oxygen radical production was unchanged. Hemodynamic registrations and myocardial oxygen consumption 90 min after failure were, however, not significantly different in control dogs and dogs pretreated with ibuprofen. Thus, in the present study, within the first 90 min of acute ischemic failure, a decrease in the ability of leucocytes to produce oxygen radicals was not related to significant changes in myocardial function. Key words: chemiluminescence; ibuprofen; _ischemia; heart failure; _leucocytes; _oxygenradicals Introduction We earlier demonstrated reduced contractile function and cell damage induced by oxygen radicals in myocardial tissue (28, 29). Several studies on ischemia, and particularly on reperfusion, have indicated that production of oxygen radicals may overwhelm the capacity of the endogenous defense mechanisms and thus be responsible for tissue damage (4, 7, 10). Possible sources of oxygen radicals are leucocytes. Stimulation of these cells leads not only to phagocytosis and release of lysosomal enzymes and arachidonic acid metabolites, but also to generation of oxygen radicals on the cell surface (1, 27). In experimental models of ischemia with subsequent reperfusion, leucocytes have been demonstrated to infiltrate the jeopardized tissue within 50 rain of reperfusion after 40 rain of ischemia. Increased margination of leucocytes in the isehemic tissue and leucocyte capillary ?lugging are earlier events and have been demonstrated at the end of 60 min of ischemia or early in reperfusion after 40 rain of ischemia (15, 25). Intravascular events such as endothelial disruption and flow perturbation may thus be due to activation (oxygen radical production) of leucocytes, and these events may lead to further reduction of hemodynamic function (6, 18, 19). 737