REGULATION OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) IN ISCHEMIC AND REPERFUSED CANINE MYOCARDIUM

Previous studies in vitro have shown an important role for intercellul ar adhesion molecule-1 (ICAM-1) in adherence interactions of canine ne utrophils with canine jugular vein endothelial cells and in cytotoxici ty of canine neutrophils for adult cardiac myocytes. To evaluate the r egulation of ICAM-1 in myocardial inflammation and its role in the pat hogenesis of myocardial ischemia and reperfusion, a series of in vivo and ex vivo studies were performed in canine animals. Systemic adminis tration of LPS elicited ICAM-1 mRNA in several tissues, including myoc ardium, which demonstrated increasing ICAM-1 staining on intercalated discs of cardiac myocytes. In ischemia and reperfusion protocols: (a) ICAM-1 mRNA was found in ischemic segments within 1 h of reperfusion a nd in both ischemic and normally perfused segments by 24 h of reperfus ion; (b) expression of ICAM-1 was detected in cardiac myocytes in the ischemic region by 6 h of reperfusion; increased expression was seen t hereafter as a function of time; (c) postischemic (but not preischemic ) cardiac lymph collected at intervals from 1 to 24 h after reperfusio n elicited ICAM-1 mRNA, ICAM-1 expression, and ICAM-1-dependent neutro phil adhesion in canine jugular vein endothelial cells and in cardiac myocytes with peak cytokine activity seen by 1 h; (d) extravascular lo calization of neutrophils was detected in ischemic areas only, and was associated with endothelium bearing high levels of ICAM-1 within 1 h of reperfusion; infiltration increased thereafter in association with increasing levels of ICAM-1 mRNA in myocardial segments and increasing levels of ICAM-1 expression on cardiac myocytes. These findings provi de the first direct evidence for inflammatory regulation of ICAM-1 in ischemic and reperfused canine myocardium. They support the hypothesis that ICAM-1 participates in neutrophil-mediated myocardial damage.