EFFECT OF CILAZAPRIL ON VENTRICULAR REMODELING ASSESSED BY DOPPLER-ECHOCARDIOGRAPHIC ASSESSMENT AND CARDIAC GENE-EXPRESSION

The purpose of this study is to determine whether the administration o f the ACE inhibitor cilazapril can lessen the adverse effects of ventr icular remodeling, including systolic and diastolic dysfunction, modul ation of fetal gene expression, increase of collagen genes, and depres sion of the sarcoplasmic reticulum (SR) Ca2+ ATPase gene in a myocardi al infarcted (MI) rat model. At 1 day after MI, the animals were rando mly assigned to cilazapril treatment or no treatment. We performed Dop pler-echocardiographic examinations and measured cardiac mRNA in rats at 1 month and 3 months after MI (each group n = 8). The weights of th e right (RV) and left ventricles (LV) in I-and 3-month MI rats were si gnificantly larger than those of the control rats. Cilazapril signific antly prevented the increase. The MI rats showed systolic dysfunction, as evidenced by decreased fractional shortening (control, 34 +/- 3% v s. MI, 17 +/- 3%; P < 0.01) and ejection fraction measured by the modi fied Simpson's method (control, 61 +/- 2% vs. MI, 36 +/- 3%; P < 0.01) in rats at 1 month after operation. MI rats showed diastolic dysfunct ion, defined as increased peak early filling velocity, increased decel eration rate of the early filling wave, decreased late filling velocit y, and an increase in the ratio of early filling to late filling veloc ity. Cilazapril significantly prevented systolic and diastolic dysfunc tion in rats after MI. The increases in B-MHC, a-skeletal actin, ANP, and collagen I and III mRNAs in the nonischemic LV and RV were signifi cantly suppressed by treatment with cilazapril. Depressed SR Ca2+-ATPa se mRNA (nonischemic LV, 0.7-fold, P < 0.05 vs, control; RV, 0.5-fold, P < 0.05 vs. control) at 3 months after MI was significantly restored to normal levels by cilazapril. Cilazapril improved the adverse remod eling process by attenuating the progression of systolic and diastolic dysfunction, and prevented abnormal cardiac gene expression following MI.