Yoshiyama M, Takeuchi K, Omura T, Izutani S, Nakamura Y, Akioka K, Kim S, Iwao H, Yoshikawa J
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Cardiovasc Drugs Ther. 1999 May;13(3):249-58. doi: 10.1023/a:1007752310881.
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.
本研究的目的是探讨地尔硫䓬对大鼠心肌梗死后心脏功能障碍的影响以及心脏基因表达的变化。在心肌梗死后的第一天，将大鼠随机分为地尔硫䓬治疗组（Dil，n = 7）和未治疗组（MI，n = 8）。然后我们对大鼠进行了多普勒超声心动图检查，并在心肌梗死后4周测量了它们的血流动力学。在这些测量之后，分析了它们的心脏mRNA。地尔硫䓬降低了平均主动脉压和心率。左心室舒张末期压力（LVEDP）和中心静脉压（CVP）分别升高至18±2 mmHg和5±1 mmHg（P < 0.01）。地尔硫䓬将LVEDP降低至14±1 mmHg（P < 0.05），但未改变CVP。MI组右心室重量明显大于对照大鼠（对照组，n = 7，0.46±0.02 g/kg vs. MI组，0.81±0.06 g/kg；P < 0.01）。MI组左心室舒张末期内径（LVDd）增加至8.8±0.3 mm（P < 0.01，对照组为6.1±0.3 mm）。地尔硫䓬可防止右心室重量增加（0.69±0.03 g/kg，P < 0.05）和LVDd增加（7.7±0.2 mm，与MI组相比P < 0.05）。MI组大鼠表现出收缩功能障碍，定义为射血分数降低（对照组为67±2% vs. MI组为36±3%，P < 0.01），以及舒张功能障碍，定义为E波减速速率（对照组为13.4±1.6 m/s² vs. MI组为30.4±3.4 m/s²；P < 0.01）。地尔硫䓬显著预防了收缩和舒张功能障碍。地尔硫䓬治疗可显著抑制非梗死左心室和右心室中β-MHC、ANP以及I型和III型胶原mRNA的增加。α-骨骼肌动蛋白在MI组中增加，并且在Dil组中增加得更多。总之，地尔硫䓬可预防实验性心肌梗死后由于左心室重构导致的心脏功能障碍和形态学改变
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