AN ANTI-CD18 ANTIBODY LIMITS INFARCT SIZE AND PRESERVES LEFT-VENTRICULAR FUNCTION IN DOGS WITH ISCHEMIA AND 48-HOUR REPERFUSION

Objectives. This study investigated whether an antibody against neutro phil adhesion protein CD18 could limit myocardial infarct size and pre sence left ventricular function after prolonged reperfusion in a canin e model. Background. Myocardial reperfusion injury is mediated in part by accumulation of activated neutrophils. Although antibodies against CD18 have been shown to reduce neutrophil influx and infarct size aft er ischemia and 3 to 4 h of reperfusion, it is unknown whether protect ion is sustained beyond this time or whether there is meaningful prese rvation of ventricular function. Methods. Dogs undergoing 90-min circu mflex coronary artery occlusion and 48-h reperfusion were randomized t o receive 1 mg/kg bodyweight of R15.7 (an anti-CD18 antibody, n = 12) or saline (control, n = 12) 10 min before reperfusion. Contrast left v entriculography was used to measure left ventricular ejection fraction and regional chord shortening at baseline, during occlusion and at 48 h, Microspheres injected during occlusion were used to measure collat eral flow and risk region size. Postmortem infarct size was measured w ith triphenyltetrazolium chloride. Results. In the dose administered, R15.7 bound to neutrophils in vivo, with >85% saturation of CD18 for > 24 h, with sustained antibody excess in the plasma, R15.7 significantl y reduced infarct size after adjusting for the effect of collateral fl ow (p = 0.0002, analysis of covariance), In a subgroup of dogs with co llateral flow <30% of nonischemic how, infarct size was reduced from 3 4.6 +/- 3.9% (mean +/- SE) of the region at risk in the control group to 19.5 +/- 3.3% in the antibody group (p = 0.008). Ejection fraction and regional chord shortening did not differ between the two groups at baseline or during occlusion, but after 48-h reperfusion, ejection fr action and inferior wall regional cord shortening (representing the in farct zone) were both higher in the R15.7 group than the control group (43.6 +/- 2.9% vs. 28.5 +/- 1.8%, p < 0.01; 2.55 +/- 0.29% vs. 1.06 /- 0.18%, p < 0.05). Conclusions. A single injection of an anti-CD18 a ntibody given before reperfusion can limit myocardial infarct size by nearly 50% and preserve global and regional left ventricular function after 48 h of reperfusion.