Pedretti R F, Colombo E, Sarzi Braga S, Ballardini L, Carù B
Division of Cardiology, Clinica del Lavoro Foundation, Istituto Ricovero e Cura a Carattere Scientifico (IRCCS), Tradate, Italy.
J Am Coll Cardiol. 1995 Mar 15;25(4):915-21. doi: 10.1016/0735-1097(94)00468-6.
Our aims were 1) to assess whether oral pirenzepine could increase indexes of cardiac vagal activity in postinfarction patients, and 2) to compare the effects of this agent with those of transdermal scopolamine.
Depression of vagal tone and reflexes predicts a poor arrhythmic outcome after myocardial infarction. Interventions for shifting the sympathovagal balance toward vagal dominance are now of increased clinical interest. Intravenous pirenzepine increases RR interval variability in normal volunteers, a finding that could have therapeutic implications if confirmed in postinfarction patients after oral administration of the drug.
In a single-blind placebo-controlled crossover trial, short-term RR interval variability and baroreceptor reflex sensitivity were evaluated in 20 patients an average of 19 +/- 6 days after infarction. Analysis was performed during control conditions and during administration of placebo, oral pirenzepine and transdermal scopolamine.
Compared with placebo, at a dose of 25 mg twice daily, pirenzepine significantly increased all time and frequency domain measures of RR interval variability and augmented baroreceptor reflex sensitivity by 60% (mean +/- 1 SD 10.4 +/- 5.9 vs. 6.5 +/- 3.2 ms/mm Hg, p = 0.0007). Pirenzepine and scopolamine showed a similar vagomimetic effect, but the overall incidence of adverse effects was lower with pirenzepine (1 [5%] of 20 vs. 10 [50%] of 20).
In patients with a recent myocardial infarction, oral pirenzepine proved equal to transdermal scopolamine in significantly increasing indexes of cardiac vagal activity. These data suggest that oral pirenzepine may have a therapeutic potential for preventing malignant ventricular arrhythmias after infarction.
我们的目标是：1）评估口服哌仑西平是否能增加心肌梗死后患者的心脏迷走神经活动指标；2）比较该药物与透皮东莨菪碱的效果。
迷走神经张力和反射的降低预示着心肌梗死后心律失常的不良结局。将交感-迷走神经平衡转向迷走神经占优势的干预措施目前在临床上受到越来越多的关注。静脉注射哌仑西平可增加正常志愿者的RR间期变异性，如果在口服该药物的心肌梗死后患者中得到证实，这一发现可能具有治疗意义。
在一项单盲安慰剂对照交叉试验中，对20例平均在心肌梗死后19±6天的患者进行了短期RR间期变异性和压力感受器反射敏感性评估。在对照条件下以及给予安慰剂、口服哌仑西平和透皮东莨菪碱期间进行分析。
与安慰剂相比，每日两次服用25mg剂量的哌仑西平可显著增加RR间期变异性的所有时域和频域指标，并使压力感受器反射敏感性提高60%（平均±1标准差为10.4±5.9对6.5±3.2ms/mm Hg，p=0.0007）。哌仑西平和东莨菪碱显示出相似的拟迷走神经作用，但哌仑西平的不良反应总发生率较低（20例中有1例[5%]，而20例中有10例[50%]）。
在近期心肌梗死患者中，口服哌仑西平在显著增加心脏迷走神经活动指标方面被证明与透皮东莨菪碱相当。这些数据表明口服哌仑西平可能具有预防梗死后恶性室性心律失常的治疗潜力。
