Cholinergic stimulation with pyridostigmine reduces ventricular arrhythmia and enhances heart rate variability in heart failure
Cholinergic stimulation with pyridostigmine reduces ventricular arrhythmia and enhances heart rate variability in heart failure
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DOI：
10.1016/s0002-8703(03)00319-3
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发表时间：
2003-09-01
影响因子：
4.8
通讯作者：
Ribeiro, JP
中科院分区：
文献类型：
--
作者：
Behling, A;Moraes, RS;Ribeiro, JP
背景：心力衰竭患者的室性心律失常密度增加和心率变异性降低与死亡风险相关。用溴化吡斯的明抑制胆碱酯酶可增加正常人的心率变异性，但其对心力衰竭患者的影响尚不清楚。在这项研究中，我们测试了短期服用吡斯的明(一种胆碱酯酶抑制剂)可以降低室性心律失常密度的假设。方法心力衰竭伴窦性心律的患者采用双盲交叉试验，随机服用安慰剂和吡斯的明(30 mg，每日3次，共2天)。24小时心电记录用于分析心律失常和测量心率变异性的时间域指标。根据室性心律失常密度将患者分为两组。心律失常组(n=11)包括每小时10次室性早搏(VPbs/h)，心率变异性组(n=12)包括24小时内室性早搏次数不超过R-R间期总数的1%的患者。结果在心律失常组，吡斯的明使室性早搏的异位活动减少65%(安慰剂266，56VPbs/h与吡斯的明173+/-49VPbs/h，P=.03)。对于心率变异性组，服用吡斯的明增加了平均R-R间期(安慰剂733+/-22ms vs吡斯的明790+/-33ms，P=0.01)，心率变异性的时间域指数连续差值的均方根(安慰剂212ms vs吡斯的明27+/-3ms，P=0.01)和相邻R-R间期不同对的百分比；50 ms(安慰剂3%+/-1%vs吡斯的明6%+/-2%，P=0.03)。结论吡氯地明可降低心力衰竭患者的室性心律失常密度，增加心率变异性，其机制可能与其类胆碱作用有关。应进行吡氯地明治疗心力衰竭的长期试验。
Background Increased ventricular arrhythmia density and reduced heart rate variability are associated with risk of death in patients with heart failure. Cholinesterase inhibition with pyridostigmine bromide increases heart rate variability in normal subjects, but its effect on patients with heart failure is unknown. In this study, we tested the hypothesis that short-term administration of pyridostigmine bromide, a cholinesterase inhibitor, reduces ventricular arrhythmia density. and increases heart rate variability in patients with congestive heart failure.Methods Patients with heart failure and in sinus rhythm participated in a double-blind, cross-over protocol, randomized for placebo and pyridostigmine (30 mg orally 3 times daily for 2 days). Twenty-four hour electrocardiographic recordings were performed for arrhythmia analysis and for the measurement of time domain indices of heart rate variability. Patients were separated into 2 groups, according to their ventricular arrhythmia density. The arrhythmia group (n = 11) included patients with >10 ventricular premature beats (VPBs) per hour (VPBs/h), and the heart rate variability group (n = 12) included patients with a number of VPBs in 24 hours not exceeding 1% of the total number of R-R intervals.Results For the arrhythmia group, pyridostigmine resulted in a 65% reduction of ventricular ectopic activity (placebo 266 56 VPBs/h vs pyridostigmine 173 +/- 49 VPBs/h, P = .03). For the heart rate variability group, pyridostigmine administration increased mean R-R interval (placebo 733 +/- 22 ms vs pyridostigmine 790 +/- 33 ms, P = .01), and in the time domain indices of heart rate variability root-mean-square of successive differences (placebo 21 2 ms vs pyridostigmine 27 +/- 3 ms, P = .01) and percentage of pairs of adjacent R-R intervals differing-by >50 ms (placebo 3% +/- 1% vs pyridostigmine 6% +/- 2%, P = .03).Conclusion In patients with heart failure, pyriclostigmine reduced ventricular arrhythmia density and increased heart rate variability, most likely due to its cholinomimetic effect. Long-term trials with pyriclostigmine in heart failure should be conducted.