Anti-CD18 attenuates myocardial stunning in the isolated neonatal lamb heart

Cardiac surgery for congenital heart disease often results in postoperative depression of myocardial function due to myocardial ischemia and stunning. The Boston Circulatory Arrest study indicated that myocardial stunning is also observed postoperatively in the immature heart. Neonates less than 3 months of age (N = 162) experienced cardiac outputs that averaged 20% of baseline values in spite of myocardium protection with Plegisol cardioplegia. In order to minimize the effects of myocardial stunning on the immature heart, we examined the effects of preischemic administration of monoclonal antibodies to leukocyte adhesion molecule CD18 (monoclonal R15.7 [Boehringer-Ingelheim]) on the function of blood perfused neonatal lamb hearts. Heart were arrested for 2 hours with a 15 degrees C K+ cardioplegia solution. Antibody treated hearts (N = 9) had significantly better (p < 0.05) recovery of left ventricular (LV) developed pressure (83.9% +/- 2.2% vs 73.6% +/- 3.0% for controls), LV dP/dt (78.4% +/- 3.3% vs 67.4% +/- 3.4% for controls), coronary blood flow (159.5% +/- 12.2% vs 84.4% +/- 3.5% for controls), and myocardial oxygen consumption (129.8% +/- 16.5% vs 71.2% +/- 6.2% for controls) than controls. In addition, recovery of coronary vascular resistance in response to 10(-6) M acetylcholine was significantly better (p = 0.08) in antibody treated hearts (38.4% +/- 4.3%) than in control hearts (13.4 +/- 12.8%). These results support the notions that leukocyte adherence to the endothelium contributes to reperfusion injury after ischemia and that monoclonal antibodies to CD18 may reduce the effects of myocardial stunning after cardiac surgery.