INHIBITION OF NEUTROPHIL ADHESION REDUCES MYOCARDIAL INFARCT SIZE

Neutrophil accumulation and activation within the myocardium during is chemia and reperfusion has been shown to play a prominent role in the development of myocardial stunning and infarction. To determine if a s imple inhibitor of neutrophil adhesion could reduce myocardial infarct size, we administered NPC 15669 (a new antiinflammatory agent that in hibits neutrophil adhesion) to 12 pigs (6 controls, 6 NPC-treated) in a porcine model of ischemia and reperfusion injury. Each animal receiv ed a continuous infusion of either NPC (10 mg/kg intravenous bolus fol lowed by 6 mg . kg-1 . h-1 intravenous infusion) or an equal volume of normal saline solution during 1 hour of left anterior descending arte ry occlusion and 2 hours of reperfusion. There were no significant dif ferences in the preischemia, midischemia, or postischemia rate-pressur e product between control and experimental groups. The regions at risk were similar in both groups. However, the mean myocardial infarct siz e was reduced by 51% with administration of NPC 15669 (30.7% +/- 6.8%) compared with controls (62.3% +/- 5.4%; p < 0.01). These data indicat e that NPC 15669, an inhibitor of neutrophil adhesion, substantially r educes myocardial infarct size after transient left anterior descendin g artery occlusion and that adhesion of the white cell to vascular end othelium may be an important element of the pathogenesis of myocardial infarction.