Li Xia, Huang Cong-Xin, Jiang Hong, Cao Feng, Wang Teng
Department of Cardiology, People's Hospital of Wuhan University, Wuhan 430060, China.
Chin Med J (Engl). 2005 Mar 5;118(5):377-82.
Carvedilol, an antagonist of alpha1- and beta-adrenergic receptors, has shown efficacy in reducing all-cause death and arrhythmia death for ischemic heart disease and congestive heart failure in several large-scale trials. It has been found to prevent ventricular remodeling, and recently was reported to reverse down-regulation of Na+ channel in a chronic heart failure model. This study was conducted to investigate whether carvedilol could reverse the ion remodeling in a myocardial infarction model of rabbit.
After the procedure of coronary ligation, animals were randomized to placebo or carvedilol treatment (5 mg/kg). Action potentials, L-type calcium current (Ica L) and the effect of isoproterenol stimulation on Ica L were measured using whole-cell patch method. Evaluation of the expression of calcium channel subunits was carried out by RT-PCR and Western blot.
The results indicate that mean peak Ica L densities (pA/pF) at +10 mV was reduced in postinfarction myocytes (5.33 +/- 0.45, n = 25) compared to sham myocytes (6.52 +/- 0.21, n = 20). Treatment of myocardial infarction rabbits with carvedilol could restore it partially (5.91 +/- 0.39, n = 20, P < 0.05). However, steady-state activation parameters were similar in three groups. With stimulation by isoproterenol (1 micromol/L) Ica L increased in all three groups, but the increase was smaller in postinfarction myocytes. mRNA levels of calcium channel subunit CaA1 gene was decreased but CaB2a, CaB2b and CaB3 mRNA levels did not change after MI. Corresponding change in CaA1 protein was also observed.
The results demonstrate that carvedilol restores Ica L density and reverse the downregulation of CaA1 postinfarction.
卡维地洛是一种α1和β肾上腺素能受体拮抗剂，在多项大规模试验中已显示出对缺血性心脏病和充血性心力衰竭降低全因死亡和心律失常死亡的疗效。已发现其可预防心室重构，最近有报道称其可在慢性心力衰竭模型中逆转钠通道下调。本研究旨在探讨卡维地洛是否能在兔心肌梗死模型中逆转离子重构。
冠状动脉结扎术后，将动物随机分为安慰剂组或卡维地洛治疗组（5mg/kg）。采用全细胞膜片钳法测量动作电位、L型钙电流（Ica L）以及异丙肾上腺素刺激对Ica L的影响。通过RT-PCR和蛋白质印迹法评估钙通道亚单位的表达。
结果表明，与假手术组心肌细胞（6.52±0.21，n = 20）相比，梗死心肌细胞在+10mV时的平均Ica L峰值密度（pA/pF）降低（5.33±0.45，n = 25）。用卡维地洛治疗心肌梗死兔可部分恢复（5.91±0.39，n = 20，P < 0.05）。然而，三组的稳态激活参数相似。用异丙肾上腺素（1μmol/L）刺激后，三组的Ica L均增加，但梗死心肌细胞中的增加较小。心肌梗死后钙通道亚单位CaA1基因的mRNA水平降低，但CaB2a、CaB2b和CaB3的mRNA水平未改变。CaA1蛋白也有相应变化。
结果表明，卡维地洛可恢复Ica L密度并逆转心肌梗死后CaA1的下调。
