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.