With the application of early reperfusion by thrombolysis after acute MI, the importance of nontransmural infarction is increasing. We evaluated 1) the changes of LV dimension, LV fibrosis and transforming growth factor-beta1 (TGF-beta1) mRNA expression in a rat model of nontransmural infarction and 2) effects of angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ATRB) treatment after nontransmural infarction.

Female Sprague-Dawley rats were subjected to 45 minutes of coronary occlusion followed by reperfusion, and at 5 days after the operation, animals were randomized to untreated (MI-vehicle, n=19), captopril-treated (MI-captopril, n=15) and losartan-treated (MI-losartan, n=14) groups. LV dimension, measured by transthoracic echocardiography, was significantly increased at 26 days after MI, and both captopril and losartan treatment inhibited LV cavity dilatation (LV end-diastolic dimension (mm): MI-vehicle, MI-captopril, MI-losartan; 8.6 ± 0.2, 7.8 ± 0.2, 8.0 ± 0.2, p<0.05 vs. MI-vehicle each). Interstitial fibrosis was reduced with both captopril and losartan treatment (p<0.05 vs. MI-vehicle). TGF-beta1 mRNA increased 2.6 fold at 10 days (p<0.05 vs. pre-MI), and normalized at 26 days after nontransmural MI. Captopril and losartan treatment blocked the induction of TGF-beta1 expression after nontransmural MI (p=S vs. pre-MI).

After large nontransmural MI, ACEI and ATRB treatments attenuate LV remodeling and decrease interstitial fibrosis, at least partly by blocking the acute induction of TGF-beta1 mRNA expression.