Heusser Karsten, Tank Jens, Brinkmann Julia, Schroeder Christoph, May Marcus, Großhennig Anika, Wenzel Daniela, Diedrich André, Sweep Fred C G J, Mehling Heidrun, Luft Friedrich C, Jordan Jens
Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany (K.H., J.T., J.B., C.S., M.M., J.J.).
Institute of Biostatistics, Hannover Medical School, Hannover, Germany (A.G., D.W.).
J Am Heart Assoc. 2016 Jan 13;5(1):e002674. doi: 10.1161/JAHA.115.002674.
Sympathetic and parasympathetic influences on heart rate (HR), which are governed by baroreflex mechanisms, are integrated at the cardiac sinus node through hyperpolarization-activated cyclic nucleotide-gated channels (HCN4). We hypothesized that HCN4 blockade with ivabradine selectively attenuates HR and baroreflex HR regulation, leaving baroreflex control of muscle sympathetic nerve activity intact.
We treated 21 healthy men with 2×7.5 mg ivabradine or placebo in a randomized crossover fashion. We recorded electrocardiogram, blood pressure, and muscle sympathetic nerve activity at rest and during pharmacological baroreflex testing. Ivabradine reduced normalized HR from 65.9±8.1 to 58.4±6.2 beats per minute (P<0.001) with unaffected blood pressure and muscle sympathetic nerve activity. On ivabradine, cardiac and sympathetic baroreflex gains and blood pressure responses to vasoactive drugs were unchanged. Ivabradine aggravated bradycardia during baroreflex loading.
HCN4 blockade with ivabradine reduced HR, leaving physiological regulation of HR and muscle sympathetic nerve activity as well as baroreflex blood pressure buffering intact. Ivabradine could aggravate bradycardia during parasympathetic activation.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00865917.
交感神经和副交感神经对心率（HR）的影响受压力反射机制调控，通过超极化激活的环核苷酸门控通道（HCN4）在心脏窦房结整合。我们假设，伊伐布雷定阻断HCN4可选择性减弱心率及压力反射对心率的调节，而压力反射对肌肉交感神经活动的控制保持完整。
我们采用随机交叉方式，对21名健康男性给予2×7.5mg伊伐布雷定或安慰剂治疗。我们记录了静息状态及药理学压力反射测试期间的心电图、血压和肌肉交感神经活动。伊伐布雷定使标准化心率从65.9±8.1次/分钟降至58.4±6.2次/分钟（P<0.001），血压和肌肉交感神经活动未受影响。使用伊伐布雷定时，心脏和交感神经压力反射增益以及对血管活性药物的血压反应未改变。伊伐布雷定在压力反射负荷期间加重了心动过缓。
伊伐布雷定阻断HCN4可降低心率，使心率、肌肉交感神经活动的生理调节以及压力反射对血压的缓冲作用保持完整。伊伐布雷定在副交感神经激活期间可能加重心动过缓。
