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Effects of intracoronary CsA on infarct size and left ventricular remodeling after coronary occlusion in dogs.
The purpose of this study was to determine the effect of cyclosporine A (CsA) on infarct size and left ventricular (LV) remodeling after coronary occlusion. Coronary occlusion for 3 hours resulted in a large MI from ischemia and a small MI from collateral blood flow, ventricular remodeling, and altered gene expression. CsA, given immediately after reperfusion, did not affect infarct size but significantly decreased the frequency of eccentric LV remodeling. In addition, CsA significantly increased baseline mRNA levels for SERCA2a, HSP90, and RyR2 and decreased those for ERK-2, NFkappaB, Dyrk1a, and MRF-4, a known hypertrophic marker. There were no significant changes in levels of other gene markers of LV function and pathological remodeling (alpha-actin, atrial natriuretic peptide, skeletal-actin, beta-actin, aldolase B, caldesmon, transforming growth factor, connective tissue growth factor, and muscle-specific actin). Based on these findings, the authors conclude that the application of CsA after reperfusion decreases the percentage of eccentric remodeling and, therefore, the LV develops a more concentric (systolic) geometry. These findings suggest that CsA administered early during the evolution of an MI provides cardioprotection by attenuating the progression to eccentric remodeling.Q:
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