Evidence for the role of neutrophils in reperfusion injury after cold cardioplegic ischemia in neonatal lambs.

The role of neutrophils in reperfusion injury after hypothermic, cardioplegia-protected ischemia is incompletely understood but may involve neutrophil-endothelial interactions. We examined 33 isolated blood-perfused neonatal lamb hearts arrested for 2 hours with 15 degrees C potassium cardioplegic solution and reperfused with unmodified blood (group C, n = 9), with neutrophil-depleted (Sepacell filter) blood (group ND, n = 9), with the addition of CV-3988, a platelet-activating factor antagonist, to the perfusate (group NA, n = 9), and with neutrophil-depleted blood plus CV-3988 (group ND/NA, n = 6). The percent recovery of isovolumic left ventricular developed pressure at a fixed balloon volume at 30 minutes after reperfusion in groups ND (84.8% +/- 11.8%, mean +/- standard deviation), NA (89.9% +/- 11.5%), and ND/NA (87.8% +/- 6.4%) were higher than in group C (73.1% +/- 7.9%) (p less than 0.05). Groups NA (105.5% +/- 13.7%) and ND/NA (108.0% +/- 11.2%) achieved higher percent recovery of coronary blood flow than group C (84.4% +/- 10.4%) (p less than 0.05). In each heart, we also tested coronary vascular resistance response to infusion of acetylcholine 10(-6) mol/L to assess endothelial function. Percent recovery of coronary vascular resistance response to acetylcholine was higher in groups ND (56.8% +/- 31.4%), NA (56.3% +/- 17.3%), and ND/NA (58.7% +/- 24.8%) than in group C (13.3% +/- 38.3%) (p less than 0.05). These results show that, after ischemia/reperfusion, groups ND, NA, and ND/NA had better recovery of both mechanical and endothelial function than group C. The parallel changes in recovery of mechanical and endothelial function suggest that neutrophil-endothelial interactions may be a significant factor in reperfusion injury.