A CHIMERIC IGG4 MONOCLONAL-ANTIBODY DIRECTED AGAINST CD18 REDUCES INFARCT SIZE IN A PRIMATE MODEL OF MYOCARDIAL-ISCHEMIA AND REPERFUSION

Objectives. This study attempted to determine whether neutrophil seque stration in reperfused myocardium can be inhibited and infarct size re duced by treatment with a chimeric, monoclonal IgG4 antibody (CLB54) d irected against CD18 in a primate model of acute myocardial ischemia a nd reperfusion. Background. Reperfusion injury, in part mediated by ne utrophils, may limit the potential benefit of reestablishing infarct-r elated artery patency in patients with acute myocardial infarction. Me thods. Nineteen closed-chest baboons (10 control, 9 treated with CLB54 ) had the left anterior descending coronary artery occluded for 90 min , followed by 4 h of reflow. CLB54 (mean [+/-SD] 11 +/- 2 mg/kg body w eight) or saline solution was administered intravenously 20 min before reflow. Coronary flow was determined using radiolabeled microspheres, infarct size by triphenyltetrazolium chloride staining, global and re gional ventricular function by contrast ventriculography and neutrophi l accumulation by a myeloperoxidase assay. Results. Risk region size w as the same in both groups. CLB54 treatment reduced infarct size expre ssed as a percent of the risk region from 41 +/- 20% in the saline-tre ated group to 19 +/- 17% in the CLB54-treated group (p < 0.02). This w as associated with diminished myeloperoxidase activity and greater pos treperfusion coronary flow in the risk region in CLB54-treated than in control baboons. Ejection fraction declined to the same extent in bot h groups, whereas anterior wall regional cord shortening was better pr eserved in CLB54-treated baboons. Conclusions. Inhibition of neutrophi l sequestration with CLB54 administered before reperfusion reduces inf arct size, preserves ischemic zone microvascular perfusion and minimiz es the decline of regional wall motion.