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左心室肥厚（LVH）消退可预防急性缺血时致死性室性心动过速引起的心源性猝死的假设。以自发性高血压大鼠（SIIR）心脏作为高血压性LVH模型，Wistar-Kyoto大鼠（WKY）心脏作为正常心脏模型。将SHR患者分为3组，分别为：1)不治疗（SHR）， 2)卡托普利治疗（SHR- c）， 3)肼嗪治疗（SHR- h）。从12周龄到18周龄，服用降压药6周。实验于18周龄进行。虽然SHR-C和SHR-H血压均降至正常水平，但只有SHR-C出现LVH消退。观察WKY组、SHR组、SHR- c组和SHR- h组左冠状动脉结扎术后30min致死性室性心动过速。持续性室性心动过速（VT）和心室颤动（Vf）的发生率在SHR合并LVH组明显高于WKY组。卡托普利治疗显著降低了VT/Vf的发生率，而肼嗪未能降低发生率。采用常规微电极技术进行电生理研究发现，SHR和SHR- h合并LVH组的动作电位持续时间（APD）明显长于WKY组，而静息电位、动作电位振幅和最大上冲程去极化速度变化不显著。在模拟缺血时，SHR和伴有LVH的SHR- h APD缩短幅度更大，而伴有LVH退化的SHR- c APD缩短幅度与WKY相似。这些结果表明，肥厚心脏在急性缺血期间更容易发生致死性室性心动过速，因为正常区和缺血区之间apd弥散度更大。退行性肥厚心脏电不均匀性的降低可以预防致命性室性心动过速引起的心源性猝死。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