Venkatesh G, Fallen E L, Kamath M V, Connolly S, Yusuf S
Division of Cardiology, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.
Heart. 1996 Aug;76(2):137-43. doi: 10.1136/hrt.76.2.137.
To test the hypothesis that short term application of transdermal scopolamine increases heart rate variability (HRV) and restores sympathovagal balance in patients with stable congestive heart failure (CHF).
A double blind placebo controlled crossover study.
Tertiary referral centre.
Twelve patients (mean age 66 (10)) with New York Heart Association class II-IV CHF. All patients had coronary artery disease (mean left ventricular ejection fraction 26.7 (8.9) %).
Patients were randomly assigned to receive either a placebo skin patch or a transdermal scopolamine patch (Transderm, 0.05 mg/h). Patches remained in place for 48 hours with a 24 hour washout period before crossover.
HRV was derived from (a) 24 hour time domain indices (mean RR interval, standard deviation of interbeat interval, and the baseline width of the frequency distribution of RR intervals) and (b) short data set (2.2 mm) power spectral measurements using autoregressive modelling. Autospectral measures were performed in both resting supine and standing (orthostatic) states. The 24 hour Holter record was obtained during the second day of patch application.
There was a small but significant (P < 0.05) increase in all time domain HRV variables with scopolamine. There was a paradoxical fall in low frequency (LF) spectral power induced by orthostasis during baseline (-30%) and placebo (-34%) states. Conversely, scopolamine was associated with a 14% increase in LF power during orthostatic stress. Scopolamine thus significantly reduced the orthostatic fall in LF (P < 0.01) compared with either baseline or placebo values. No difference in circadian rhythm was seen between the scopolamine and placebo treatment periods. However, the abrupt fall in the high frequency (vagal) power during the early morning sleep-wake hours was reduced by scopolamine. Scopolamine was also associated with a significant rightward shift in the resting LF central frequency consistent with a vagomimetic effect.
Patients with chronic stable CHF showed a paradoxical fall in the low frequency (sympathetic) power during orthostatic stress. Transdermal scopolamine applied over a 48 hour period partially restored the balance between sympathetic tone and vagal activity in CHF patients and maintained this balance during orthostatic stress.
验证以下假设，即短期应用透皮东莨菪碱可增加稳定型充血性心力衰竭（CHF）患者的心率变异性（HRV）并恢复交感神经 - 迷走神经平衡。
双盲安慰剂对照交叉研究。
三级转诊中心。
12例纽约心脏协会心功能II - IV级的CHF患者（平均年龄66（10）岁）。所有患者均患有冠状动脉疾病（平均左心室射血分数26.7（8.9）%）。
患者被随机分配接受安慰剂皮肤贴片或透皮东莨菪碱贴片（Transderm，0.05 mg/h）。贴片贴敷48小时，交叉前有24小时的洗脱期。
HRV通过以下方式得出：（a）24小时时域指标（平均RR间期、心跳间期标准差以及RR间期频率分布的基线宽度）；（b）使用自回归模型的短数据集（2.2分钟）功率谱测量。在静息仰卧位和站立（直立）状态下均进行自谱测量。在贴片应用的第二天获取24小时动态心电图记录。
使用东莨菪碱后所有时域HRV变量均有小幅但显著（P < 0.05）增加。在基线（-30%）和安慰剂（-34%）状态下，直立位引起的低频（LF）谱功率出现反常下降。相反，在直立应激期间，东莨菪碱使LF功率增加14%。因此，与基线或安慰剂值相比，东莨菪碱显著降低了直立位时LF的下降（P < 0.01）。在东莨菪碱和安慰剂治疗期间，昼夜节律未见差异。然而，东莨菪碱减少了清晨睡眠 - 觉醒时段高频（迷走神经）功率的突然下降。东莨菪碱还使静息LF中心频率显著右移，这与拟迷走神经效应一致。
慢性稳定型CHF患者在直立应激期间低频（交感神经）功率出现反常下降。48小时应用透皮东莨菪碱可部分恢复CHF患者交感神经张力和迷走神经活动之间的平衡，并在直立应激期间维持这种平衡。
