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.


CONCLUSIONS
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.
Metzler
B
B
Division of Cardiology, Department of Internal Medicine, University of Innsbruck, Innsbruck, Austria.
Mair
J
J
Lercher
A
A
Schaber
C
C
Hintringer
F
F
Pachinger
O
O
Xu
Q
Q
D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D007527:Isoenzymes / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007962:Leukocytes / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D023421:Models, Animal; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018709:Statistics, Nonparametric; D020107:Troponin T / Q000097:blood; D020257:Ventricular Remodeling
D007527:Isoenzymes; D016177:Macrophage-1 Antigen; D020107:Troponin T; D018799:Intercellular Adhesion Molecule-1; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1; D003402:Creatine Kinase