Acute ivabradine treatment reduces heart rate without increasing atrial fibrillation inducibility irrespective of underlying vagal activity in dogs
Acute ivabradine treatment reduces heart rate without increasing atrial fibrillation inducibility irrespective of underlying vagal activity in dogs
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DOI：
10.1007/s00380-016-0922-y
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发表时间：
2017-04
影响因子：
1.5
通讯作者：
K. Uemura;M. Inagaki;C. Zheng;T. Kawada;Meihua Li;M. Fukumitsu;M. Sugimachi
中科院分区：
文献类型：
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作者：
K. Uemura;M. Inagaki;C. Zheng;T. Kawada;Meihua Li;M. Fukumitsu;M. Sugimachi
伊伐布雷定是一种心动过缓药物，已被证明可在急性心脏病护理环境中稳定降低患者心率（HR）。然而，房颤（AF）风险与急性伊伐布雷定治疗之间的相关性仍然是一个有争议的临床问题，尚未进行彻底研究。伊伐布雷定治疗诱导的心动过缓和异常心房不应性可能增加AF诱导的脆弱性，尤其是当迷走神经同时激活时。我们旨在通过实验研究急性伊伐布雷定治疗伴/不伴迷走神经激活对AF诱导的影响。在16只麻醉犬上，制备颈迷走神经用于电刺激（VS）。心房短阵起搏测定房颤诱导率（AFIR）。在基线、VS输送期间（单独VS）、伊伐布雷定0.5 mg/kg（n= 8，伊伐布雷定组）或生理盐水（n = 8，生理盐水组）静脉注射后以及VS输送期间（药物+VS）再次连续获得HR、心房动作电位时程（APD）、心房有效不应期（ERP）和AFIR。在伊伐布雷定组中，与基线相比，伊伐布雷定单药治疗显著降低HR，而与VS单药治疗相比，伊伐布雷定+VS显著降低HR。与预期相反，伊伐布雷定组和生理盐水组之间APD趋势、APD时间离散度、ERP和AFIR无显著差异。无论是否注射伊伐布雷定或生理盐水，VS均显著缩短APD和ERP，并增加AFIR。有趣的是，尽管伊伐布雷定注射后的心动过缓比VS单独给药时更严重，但伊伐布雷定注射后的AFIR显著低于VS单独给药期间。我们得出结论，尽管有强烈的心动过缓作用，但无论基础迷走神经活动如何，急性伊伐布雷定治疗均不会增加AF诱导率。本研究可能支持伊伐布雷定在急性心脏病护理中的安全性。
Ivabradine, a bradycardic agent, has been shown to stably reduce patient’s heart rate (HR) in the setting of acute cardiac care. However, an association between atrial fibrillation (AF) risk and acute ivabradine treatment remains a controversial clinical issue, and has not been thoroughly investigated. Bradycardia and abnormal atrial refractoriness induced by ivabradine treatment may enhance vulnerability to AF induction, especially when vagal nerve is concurrently activated. We aimed to experimentally investigate the effects of acute ivabradine treatment with/without concurrent vagal activation on AF inducibility. In 16 anesthetized dogs, cervical vagal nerves were prepared for electrical stimulation (VS). AF induction rate (AFIR) was determined by atrial burst pacing. HR, atrial action potential duration (APD), atrial effective refractory period (ERP), and AFIR were obtained consecutively at baseline, during delivery of VS (VS alone), after intravenous injection of ivabradine 0.5 mg/kg (n= 8, ivabradine group) or saline (n= 8, saline group), and again during VS delivery (drug+VS). In the ivabradine group, ivabradine alone significantly lowered HR compared to baseline, while ivabradine+VS significantly lowered HR compared to VS alone. Contrary to expectations, there were no significant differences in trends of APD, temporal dispersion of APD, ERP, and AFIR between ivabradine and saline groups. Irrespective of whether ivabradine or saline was injected, VS significantly shortened APD and ERP, and increased AFIR. Interestingly, although bradycardia in response to ivabradine injection was more intense than that to VS alone, AFIR was significantly lower after ivabradine injection than during VS alone. We conclude that, despite its intense bradycardic effect, acute ivabradine treatment does not increase AF inducibility irrespective of underlying vagal activity. This study may constitute support for the safety of using ivabradine in the setting of acute cardiac care.