Libersa C C, Caron J F, Kacet S, Lesenne M, Werquin S, Dupuis B A, Danays T, Lekieffre J P
Laboratoire de Pharmacologie Hospitalière, Faculté de Médecine, Lille, France.
Clin Cardiol. 1988 Jul;11(7):454-60. doi: 10.1002/clc.4960110704.
At the present time, there is no satisfactory pharmacological treatment for arrhythmia or conduction disorders induced by or aggravated by vagal hypertonia. The limited duration of action of the atropine derivatives currently available justifies the development of new compounds with expected longer acting duration. The aim of this study was to compare the effects of a single blind intravenous injection of ipratropium bromide to those of atropine sulfate in 22 patients. These patients were studied with continuous Holter recordings for three days. During the second and the third nights (patient sleeping), boluses of atropine (0.03 mg/kg) and of ipratropium bromide (0.03 mg/kg), respectively, were added to a continuous saline intravenous infusion. Accurate ECG analysis allowed determination of maximal heart rate peak, timing of maximal heart rate, variations in sinus cycle length, atrioventricular conduction, and durations of drug action. A nonsuggestive questionnaire was presented to patients to detect possible occurrence of side effects. The mean maximal heart rate rose significantly (p less than 0.001) for atropine (+46.2%) and for ipratropium bromide (+57.4%). The effects obtained with ipratropium bromide on the heart rate lasted nearly twice as long as those obtained with atropine (respectively, 120 +/- 38.4 min and 70 +/- 30 min- for the pharmacological half-life). Common minor muscarinic side effects (dryness of the mouth) were noted with the two drugs. In conclusion, this comparative intraindividual study confirmed the prolonged vagolytic effects of intravenous ipratropium bromide, which may be valuable in the treatment of patients with vagally mediated automaticity and conduction disturbances.
目前，对于由迷走神经张力亢进诱发或加重的心律失常或传导障碍，尚无令人满意的药物治疗方法。现有阿托品衍生物的作用持续时间有限，这使得开发预期作用持续时间更长的新化合物成为必要。本研究的目的是比较22例患者单次盲法静脉注射异丙托溴铵与硫酸阿托品的效果。对这些患者进行了连续三天的动态心电图记录研究。在第二晚和第三晚（患者睡眠期间），分别将阿托品（0.03mg/kg）和异丙托溴铵（0.03mg/kg）推注加入持续静脉输注的生理盐水中。精确的心电图分析可确定最大心率峰值、最大心率出现时间、窦性周期长度变化、房室传导以及药物作用持续时间。向患者发放了一份无诱导性的问卷，以检测可能出现的副作用。阿托品（+46.2%）和异丙托溴铵（+57.4%）使平均最大心率显著升高（p<0.001）。异丙托溴铵对心率的作用持续时间几乎是阿托品的两倍（药理半衰期分别为120±[+/-]38.4分钟和70±[+/-]30分钟）。两种药物均出现了常见的轻微毒蕈碱样副作用（口干）。总之，这项个体内比较研究证实了静脉注射异丙托溴铵具有延长的抗迷走神经作用，这对于治疗由迷走神经介导的自律性和传导障碍患者可能具有重要价值。
