DOPPLER-ECHOCARDIOGRAPHIC ASSESSMENT AND CARDIAC GENE-EXPRESSION ANALYSIS OF THE LEFT-VENTRICLE IN MYOCARDIAL INFARCTED RATS

The purpose of this study was to examine cardiac geometry and function by Doppler echocardiography and to analyze mRNA expression of cardiac phenotype and extracellular matrix in myocardial infarcted rats. Dopp ler echocardiograms and hemodynamics were measured 2 weeks after myoca rdial infarction (MI). mRNA levels in the non-infarcted left ventricle (LV) and infarct site were measured by Northern blot analysis. LV int ernal diastolic dimension was greater in infarcted (MI) than in sham-o perated rats (control) (MI 7.2+/-0.3 mm vs control 4.6+/-0.3 mm, p<0.0 1). The fractional shortening decreased in MI rats CMI 32+/-4% vs cont rol 61+/-3%, p<0.01). Peak early filling velocity increased in MI rats (MI 91+/-5 cm/sec vs control 72+/-4 cm/sec, p<0.05), and deceleration rate of the early filling wave was more rapid in rats with MI (MI 25. 1+/-2.8 m/sec(2) vs control 12.4+/-1.7 m/sec(2), p<0.01). Late filling velocity decreased (MI 16+/-3 cm/sec vs control 35+/-6 cm/sec, p<0.05 ), resulting in a marked increase in the ratio of early filling to lat e filling (MI 7.1+/-1.2 vs control 2.5+/-0.4, p<0.01). mRNA levels for beta-myosin heavy chain (beta-MHC), n-skeletal actin, atrial natriure tic polypeptide (ANP), collagen types I and III, and matrix metallopro teinase 2 (MMP-2) in the non-infarcted LV increased significantly by 1 .8-, 2.4-, 4.7-, 2.6-, 2.1- (all p<0.01) and 1.4-fold (p<0.05), respec tively, compared with sham-operated myocardium. In the infarct site, m RNA levels for transforming growth factor (TGF)-beta(1), collagen type s I and III and MMP-2 significantly increased by 3.2-, 11.0-, 9.7-, an d 6.3-fold (all p<0.01), respectively, compared with sham-operated myo cardium. Myocardial infarcted rat was characterized by cavity dilation and marked abnormalities of systolic and diastolic function, accompan ied by a shift of myocytes to fetal phenotype and activation of collag en genes in the non-infarcted myocardium.