Mouse model of myocardial remodelling after ischemia: role of intercellular adhesion molecule-1

Objective: We studied the effects of temporary myocardial ischemia and repe rfusion on myocyte injury and ventricular remodelling in wildtype and inter cellular adhesion molecule-1- (ICAM-1) deficient mice. Methods: ICAM-1-/- a nd ICAM-1+/+ mice were subjected to 30 min of myocardial ischemia and subse quent reperfusion for 2 h, 1 week and 3 weeks, respectively. The evaluation of tissue damage and scar size was performed with histological sections st ained with hematoxilin and eosin. Serum levels of troponin T, creatine kina se and lactate dehydrogenase isoenzyme 1 were evaluated as an index of card iac cellular damage. Immunohistological analysis was employed to determine cell compositions in ischemic regions. Results: After myocardial ischemia ( 30 min) and 2 h reperfusion, elevation in serum troponin T, creatine kinase and lactate dehydrogenase isoenzyme 1 were found in both groups, but signi ficantly reduced in ICAM-1-/- mice compared with wildtype mice (P<0.05). Ab sence of a functional ICAM-1 gene in ICAM-1-/- mice resulted in a marked re duction of ischemia-reperfusion injury at the early stage. The damage score and size of the infarct area were lower in ICAM-1 -/- mice by 30 min of is chemia and 2 h of reperfusion (1.4+/-0.54 vs. 2.4+/-0.47, P<0.05). The perc entage of MAC-1-positive cells in the ischemic region and the border zone w as also significantly diminished in groups of ICAM-1-/- mice. Surprisingly, the scar size in ventricles in animals 1 or 3 weeks after ischemia was sim ilar between ICAM-1-/- and ICAM-1+/+ mice, although the number of infiltrat ed MAC-1 positive cells in the scar in wildtype mice was higher. Conclusion : Our results demonstrate that the absence of ICAM-1 expression results in less myocardial damage induced by ischemia-reperfusion at the early stage, but does not influence the size of myocardial infarction and scar formation . (C) 2001 Elsevier Science B.V. All rights reserved.