Electrophysiological effect of rotigaptide in rabbits with heart failure.

Electrophysiological effect of rotigaptide in rabbits with heart failure.
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罗替肽肽对家兔心力衰竭的电生理作用

DOI:
10.5114/aoms.2012.31385
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发表时间:
2014-05-12
期刊:
Archives of medical science : AMS
影响因子:
--
通讯作者:
Huang H
Huang H
中科院分区:
其他
文献类型:
--
作者:
Liu Y;Li H;Xia W;Yu S;Huang C;Huang H

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罗替加肽是一种新的抗心肌缺血肽,最近发现它可以增加心肌连接电导,预防缺血性室性心动过速。本研究旨在探讨罗替加肽对心力衰竭(HF)家兔室性心律失常易感性的影响及其机制。材料与方法采用慢性容量-压力超负荷诱发HF。静脉输注罗替加肽后,进行电生理检查,记录单相动作电位(MAP),测定有效不应期(ERP)和室颤阈值(VFT),并评估室性心律失常的易感性。实时荧光定量PCR检测细胞间隙连接蛋白43(Cx43)mRNA表达的变化。结果心衰组Cx43 mRNA表达下调,有效不应期延长,VFT缩短(p < 0.05)。这些变化导致室性快速性心律失常(VT/VF)的脆弱性增加。给予罗替加肽缩短了ERP(113.3 ±8.6 ms vs. 131.7 ±12.5 ms,p < 0.05),恢复了VFT(15.0 ±2.0 V vs. 6.3 ±1.4 V,p < 0.05),并降低了VT/VF的易感性。然而,短期罗替加肽治疗对MAP持续时间(90%复极时的MAP持续时间:169.3 ±6.0 ms vs. 172.7 ±6.2 ms,p > 0.05)或连接蛋白43 mRNA表达无显著影响(p > 0.05)。结论罗替加肽可降低心力衰竭兔的ERP,提高VFT,降低室性心律失常的易感性,而不改变Cx43的表达。它可能是一种很有前途的预防HF室性心律失常的抗心律失常药物。
Introduction Rotigaptide is a new anti-arrhythmic peptide, which has recently been found to increase junctional conductance and prevent ischemia-induced ventricular tachycardia. In this study, we attempted to investigate the effects and mechanisms of rotigaptide on the vulnerability to ventricular arrhythmias in rabbits with heart failure (HF). Material and methods Chronic volume-pressure overload was used to induce HF. After rotigaptide infusion, an electrophysiological study was performed to record monophasic action potential (MAP), determine the effective refractory period (ERP) and ventricular fibrillation threshold (VFT), and assess the susceptibility to ventricular arrhythmia. Finally, real-time PCR was used to detect the changes of connexin 43 (Cx43) mRNA expression. Results HF rabbits exhibited significant down-regulation of Cx43 mRNA, increase of effective refractory period (ERP) and decrease of VFT (p < 0.05, respectively). These changes resulted in an increase of vulnerability to ventricular tachyarrhythmias (VT/VF). Rotigaptide administration shortened ERP (113.3 ±8.6 ms vs. 131.7 ±12.5 ms, p < 0.05), restored VFT (15.0 ±2.0 V vs. 6.3 ±1.4 V, p < 0.05), and decreased the vulnerability to VT/VF. However, short-term rotigaptide treatment had no significant effect on MAP duration (MAP duration at 90% repolarization: 169.3 ±6.0 ms vs. 172.7 ±6.2 ms, p > 0.05) or connexin 43 mRNA expression (p > 0.05). Conclusions Rotigaptide decreases the ERP, elevates VFT, and reduces the vulnerability to ventricular arrhythmias without changing Cx43 expression in rabbits with HF. It may be a promising antiarrhythmic drug for preventing ventricular arrhythmia in HF.
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