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

Objective: We studied the effects of temporary myocardial ischemia and reperfusion on myocyte injury and ventricular remodelling in wildtype and intercellular adhesion molecule-1- (ICAM-1) deficient mice. Methods: ICAM-1−/− and ICAM-1+/+ mice were subjected to 30 min of myocardial ischemia and subsequent reperfusion for 2 h, 1 week and 3 weeks, respectively. The evaluation of tissue damage and scar size was performed with histological sections stained with hematoxilin and eosin. Serum levels of troponin T, creatine kinase and lactate dehydrogenase isoenzyme 1 were evaluated as an index of cardiac 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 significantly reduced in ICAM-1−/− mice compared with wildtype mice (P<0.05). Absence of a functional ICAM-1 gene in ICAM-1−/− mice resulted in a marked reduction 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 ischemia and 2 h of reperfusion (1.4±0.54 vs. 2.4±0.47, P<0.05). The percentage of MAC-1-positive cells in the ischemic region and the border zone was also significantly diminished in groups of ICAM-1−/− mice. Surprisingly, the scar size in ventricles in animals 1 or 3 weeks after ischemia was similar between ICAM-1−/− and ICAM-1+/+ mice, although the number of infiltrated 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.