Effect of chronic antihypertensive treatment on ischemic lethal ventricular tachyarrhythmias and electrophysiological property in hypertrophied rat hearts

本研究的目的是验证一种假说，即左心室肥厚(LVH)的消退可防止急性缺血期间致死性室性心律失常所致的心脏性猝死。自发性高血压大鼠(SIIR)的心脏作为高血压左心室肥厚模型，Wistar-京都大鼠(WKY)的心脏作为正常血压心脏。SHR分为3组：SHR组(SHR)、SHR-C组(SHR-C)、SHR-H组(SHR-H)。给药时间为6周，12~18周龄。实验在18周龄时进行。尽管SHR-C和SHR-H的血压均降至正常水平，但只有SHR-C表现出左心室肥厚的消退。对WKY组、SHR组、SHR-C组和SHR-H组在结扎左冠状动脉后30min内诱发的致死性室性快速性心律失常进行研究。持续性室性心动过速(VT)和Ve…的发生率SHR合并LVH的室颤(VF)明显高于WKY组。卡托普利治疗显着降低了室速/室颤的发生率，尽管肼丙嗪未能降低其发生率。常规微电极电生理研究表明，SHR和SHR-H伴LVH时，动作电位时程较WKY明显延长，而静息电位、动作电位波幅和最大除极上移速度无明显变化。在模拟缺血过程中，SHR和SHR-H伴LVH组APDS缩短幅度较大，而SHR-C伴LVH消退组APDS仅略短于WKY组。这些结果表明，肥厚的心脏在急性缺血期间更容易发生致死性室性心律失常，这是因为APDS在正常和缺血区之间的离散度更大。减少退行性肥厚心脏的电不均质性，可预防致死性室性心律失常所致的心源性猝死。较少

The purpose of the study is to test the hypothesis that regression of left ventricular hypertrophy (LVH) prevents sudden cardiac death caused by lethal ventricular tachyarrhytmias during acute ischemia. Hearts from spontaneously hypertensive rats (SIIR) were used as a model of hypertensive LVH and those from Wistar-Kyoto rats (WKY) were served as normotensive hearts. SHRs were divided into 3 groups, as follows: 1) SHRs with no treatment (SHR), 2) SHRs treated with captopril (SHR-C), 3) SHRs treated with hydralazine (SHR-H). The antihypertensive agents were given for 6 weeks, from 12 to 18 weeks of age. Experiments were performed at 18 weeks of age. Although blood pressure in SHR-C and SHR-H were equally lowered to normal level, only SHR-C showed regression of LVH. Lethal ventricular tachyarrhythmias induced during 30 minutes after ligation of the left coronary artery were studied in the 4 groups (WKY, SHR, SHR-C and SHR-H). The incidence of sustained ventricular tachycardia (VT) and ve … More ntricular fibrillation (Vf) was significantly higher in SHR with LVH than in WKY. Treatment with captopril significantly reduced the incidence of VT/Vf although hydralazine failed to reduce the incidence. The electrophysiological study using conventional microelectrode techniques revealed that in SHR and SHR-H with LVH, action potential duration (APD) was much more prolonged than in WKY while resting potential, action potential amplitude and maximum upstroke velocity of depolarization did not change significantly. The APDs in SHR and SHR-H with LVH shortened to a greater extent during simulated ischemia, while in SHR-C with regressed LVH APD shortened only a little similar to that in WKY. These results suggest that hypertrophied hearts have a greater susceptibility to lethal ventricular tachyarrhythmias during acute ischemia because of greater APDs dispersion between the normal and ischemic zone. The reduction of electrical inhomogeneity in regressd hypertrophied hearts may prevent sudden cardiac death caused by lethal ventricular tachyarrhythmias. Less