Polymorphonuclear leukocytes (i.e. neutrophils) significantly mediate damage in
myocardial ischemia followed by reperfusion. In the present study, the cardioprotective effects of a humanized form of a
monoclonal antibody directed against
L-selectin designated
monoclonal antibody (mAb) HuDREG-200 were examined in a feline model of 90-min
myocardial ischemia followed by 270 min of reperfusion. In preliminary studies, flow cytometric analysis indicated that HuDREG-200 binds to feline neutrophils. In vitro administration of mAb HuDREG-200 significantly inhibited (P < .01) adherence of unstimulated neutrophils to ischemic-reperfused coronary endothelium in a concentration-dependent manner. Humanized DREG-200 (2 mg/kg) administered 10 min before reperfusion significantly attenuated myocardial
necrosis compared to an isotype-matched humanized control mAb (HuABL364) which does not bind to
L-selectin (14 +/- 3 vs. 29 +/- 3%
necrosis/area-at-risk, P < .01), representing a 52% reduction in myocardial
necrosis. This myocardial preservation also was related to reduced
creatine kinase release and improved recovery of cardiac contractility (i.e. left ventricular dP/dtmax). Moreover, endothelial function, as assessed by relaxation to
acetylcholine, also was significantly preserved in ischemic-reperfused coronary arteries isolated from cats treated with mAb HuDREG-200 compared to mAb HuABL364 (68 +/- 6 vs. 18 +/- 5, P < .01). Thus, a humanized anti-
L-selectin mAb appears to be an effective means of preserving the ischemic myocardium from
reperfusion injury and of preserving myocardial contractile function, at least during the early reperfusion period.