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Prior studies have shown that leukocytes are important in reperfusion injury after normothermic ischemia, and recently discovered leukocyte adhesion molecules that bind to endothelial ligands may be involved in this process. No studies on the role of leukocyte adhesion molecules in hypothermic ischemia are available.We assessed the effect of preischemic administration of monoclonal antibody to the leukocyte adhesion molecule CD18 on recovery of isolated blood-perfused neonatal lamb hearts arrested for 2 hours with 15°C K+ cardioplegic solution by comparing nine antibody-treated and nine control hearts. At 30 minutes after reperfusion, antibody-treated hearts compared with control hearts had better percent recovery of maximum left ventricular (LV) developed pressure (83.9±2.2% versus 73.6±3.0%, mean±SEM), LV dP/dt (78.4±3.3% versus 67.4±3.4%), coronary blood flow (159.5±12.2% versus 84.4±3.5%), and myocardial oxygen consumption (129.8±16.5% versus 71.2±6.2%) (all p<0.05). In each heart, we also tested coronary vascular resistance (CVR) response to 10−6 mol/l acetylcholine (ACh) infusion to assess endothelial function. Percent recovery of CVR response to ACh was higher in antibody-treated hearts (38.4±4.3%) than control hearts (13.4±12.8%) (p=0.08).These results suggest that leukocyte adherence to endothelium mediated by CD18 plays an important role in reperfusion after hypothermic ischemia. Antibody to CD18 may be useful in myocardial and endothelial protection during surgically induced ischemia.