Effect of diltiazem on cardiac remodeling in rats assessed by Doppler echocardiography and mRNA expression

Abstract

The purpose of this study was to examine the effect of diltiazem on cardiac dysfunction and the change in cardiac gene expression after myocardial infarction in rats. On the first day after myocardial infarction, rats were randomly assigned to a diltiazem treatment (Dil, n = 7) or an untreated group (MI, n = 8). We then performed Doppler echocardiographic examinations on the rats and measured their hemodynamics at 4 weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed. Diltiazem decreased the mean aortic pressure and heart rate. Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 18 +/- 2 mmHg and 5 +/- 1 mmHg (P < 0.01). Diltiazem reduced LVEDP to 14 +/- 1 mmHg (P < 0.05), but it did not change CVP. The weight of the right ventricle in MI was significantly larger than in the control rats (control, n = 7, 0.46 +/- 0.02 g/kg vs. MI, 0.81 +/- 0.06 g/kg; P < 0.01). The left ventricular end-diastolic dimension (LVDd) in MI increased to 8.8 +/- 0.3 mm (P < 0.01, control, 6.1 +/- 0.3 mm). Diltiazem prevented an increase in the weight of the right ventricle (0.69 +/- 0.03 g/kg, P < 0.05) and LVDd (7.7 +/- 0.2 mm, P < 0.05 to MI). The rats within MI showed systolic dysfunction, defined by a decreased ejection fraction (control, 67 +/- 2% vs. MI, 36 +/- 3%, P < 0.01), and diastolic dysfunction, defined by the E-wave deceleration rate (control, 13.4 +/- 1.6 m/s2 vs. MI, 30.4 +/- 3.4 m/s2; P < 0.01). Diltiazem significantly prevented systolic and diastolic dysfunction. The increases in beta-MHC, ANP, and collagen type I and III mRNAs in the noninfarcted left ventricle and right ventricle were significantly suppressed by treatment with diltiazem. alpha-Skeletal actin increased in MI, and alpha-skeletal actin was more increased with Dil. In conclusion, diltiazem prevents cardiac dysfunction and morphological change due to left ventricular remodeling after experimental myocardial infarction.