De Ferrari G M, Mantica M, Vanoli E, Hull S S, Schwartz P J
Centro di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Italy.
J Am Coll Cardiol. 1993 Nov 1;22(5):1327-34. doi: 10.1016/0735-1097(93)90538-c.
OBJECTIVES: The goal of this study was to assess the hypothesis that transdermal scopolamine would increase vagal activity in patients after myocardial infarction. BACKGROUND: In postmyocardial infarction patients, low heart rate variability and reduced baroreceptor reflex sensitivity are associated with increased mortality. Accordingly, there is an increasing interest in a mechanism for shifting the sympathovagal balance toward vagal dominance. METHODS: The effects of transdermal administration of scopolamine on heart rate variability and baroreceptor reflex sensitivity were assessed in 20 patients (mean age 59 +/- 11 years) by pharmacologic washout 14 +/- 3 days after myocardial infarction. Heart rate variability and baroreceptor reflex sensitivity were measured 24 h after application of the scopolamine patch and compared with the values measured before scopolamine and after application of a placebo patch. The following variables were derived from a 15-min electrocardiographic recording: the mean RR interval and its standard deviation, the mean square successive difference, the percent of intervals differing > 50 ms from the preceding RR interval and the low and high frequency areas resulting from power spectral analysis. RESULTS: The placebo patch had no effect on the variables measured. Scopolamine increased both heart rate variability and baroreceptor reflex sensitivity significantly. Specifically, the mean RR interval and its standard deviation increased by 7.1% (p = 0.01) and 25% (p = 0.004), respectively. The mean square successive difference increased by 38% (p = 0.0003) and the percent of intervals differing > 50 ms from the preceding interval by 100% (p = 0.001). The ratio of low to high frequency areas of the power spectrum decreased by 24% (p = 0.02), and baroreceptor reflex sensitivity increased by 42% (p = 0.0006). These effects were also evident in patients with very low initial values. Side effects were minimal. CONCLUSIONS: Transdermal scopolamine increased measures of heart rate variability and baroreceptor reflex sensitivity in patients with a recent myocardial infarction toward values associated with a better prognosis. Pharmacologic modulation of the autonomic balance by scopolamine or related drugs deserves evaluation as a new and promising approach to reduce risk after myocardial infarction.
目的：本研究的目的是评估透皮给予东莨菪碱可增加心肌梗死后患者迷走神经活性这一假说。 背景：在心肌梗死后患者中，心率变异性降低和压力感受器反射敏感性降低与死亡率增加相关。因此，人们越来越关注一种能使交感-迷走神经平衡向迷走神经占优势转变的机制。 方法：通过药物洗脱法，在20例（平均年龄59±11岁）心肌梗死后14±3天的患者中评估透皮给予东莨菪碱对心率变异性和压力感受器反射敏感性的影响。在应用东莨菪碱贴片24小时后测量心率变异性和压力感受器反射敏感性，并与应用东莨菪碱前及应用安慰剂贴片后的测量值进行比较。以下变量来自15分钟的心电图记录：平均RR间期及其标准差、逐次差值均方、与前一个RR间期相差>50毫秒的间期百分比以及功率谱分析得出的低频和高频区域。 结果：安慰剂贴片对所测变量无影响。东莨菪碱显著增加了心率变异性和压力感受器反射敏感性。具体而言，平均RR间期及其标准差分别增加了7.1%（p = 0.01）和25%（p = 0.004）。逐次差值均方增加了38%（p = 0.0003），与前一个间期相差>50毫秒的间期百分比增加了100%（p = 0.001）。功率谱低频与高频区域的比值降低了24%（p = 0.02），压力感受器反射敏感性增加了42%（p = 0.0006）。这些效应在初始值非常低的患者中也很明显。副作用极小。 结论：透皮给予东莨菪碱可使近期心肌梗死患者的心率变异性和压力感受器反射敏感性指标向与更好预后相关的值增加。东莨菪碱或相关药物对自主神经平衡的药理调节作为一种降低心肌梗死后风险的新的有前景的方法值得评估。
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