Myocardial ischemia-reperfusion injury in CD18- and ICAM-1-deficient mice

Previous studies have demonstrated that circulating neutrophils (PMNs) cont ribute to the pathophysiology of myocardial ischemia-reperfusion (MYR) inju ry. PMN-endothelial cell interactions are highly regulated by adhesive inte ractions between PMN CD11/ CD18 and coronary endothelial cell intercellular adhesion molecule-1 (ICAM-1). We investigated the effects of MI/R in wild- type, CD18-, and ICAM-1-deficient (-/-) mice. Wildtype (n = 6), CD18 -/- (n . = 6), and ICAM-1 -/- (n = 6) mice were subjected to 30 min of myocardial ischemia and 120 min of reperfusion to determine the extent of PMN infiltra tion and myocardial cell necrosis. Myocardial infarction (% of the area at risk) was 45.1 +/- 5.9 in wild-type mouse hearts. In contrast, the extent o f myocardial infarction was significantly (P < 0.05) reduced in the CD18 (1 9.3 +/- 5.1%)- and ICAM-1 (17.9 +/- 3.2%)-deficient mice. Similarly, PMN in filtration into the ischemic-reperfused myocardium was attenuated by 54% in the CD18 -/- mice and by 32% in ICAM-1 -/- mice compared with wild-type he arts. Deficiency in either CD18 or ICAM-1 expression results in a marked re duction in PMN accumulation and myocardial necrosis after acute MI/R.