De Ferrari G M, Salvati P, Grossoni M, Ukmar G, Vaga L, Patrono C, Schwartz P J
Istituto di Clinica Medica 2, Universitá di Milano, Italy.
J Am Coll Cardiol. 1993 Jul;22(1):283-90. doi: 10.1016/0735-1097(93)90845-r.
The goal of the present study was to evaluate the antifibrillatory and hemodynamic effects of pharmacologic muscarinic activation and to compare them with those of beta-adrenergic blockade.
Recent studies suggest a correlation between increased vagal activity and a reduced incidence of sudden cardiac death. Electrical stimulation of the vagus nerve reduces the incidence of ventricular fibrillation in a conscious animal model of sudden cardiac death.
Eleven dogs with healed anterior myocardial infarction, in which a 2-min left circumflex coronary artery occlusion during exercise caused ventricular fibrillation, were studied. They underwent subsequent tests with saline solution, propranolol (1 mg/kg body weight), methacholine (0.5 microgram/kg per min) and oxotremorine (8 micrograms/kg).
In the test with saline solution, 100% of the dogs developed ventricular fibrillation; this occurred in only 10% of the tests with propranolol (95% confidence interval 0.2% to 44%; p < 0.001), 60% of the tests with methacholine (95% confidence interval 26% to 88%, p = 0.05) and 37.5% of the tests with oxotremorine (95% confidence interval 8% to 75%, p = 0.005). Propranolol and oxotremorine significantly reduced heart rate compared with saline solution, whereas methacholine did not. Propranolol significantly reduced maximal first derivative of left ventricular pressure, (dP/dtmax), particularly during myocardial ischemia, compared with the other treatments (2,391 +/- 582 mm Hg/s [mean +/- 1 SD] with propranolol vs. 4,226 +/- 1,237, 4,922 +/- 584 and 4,358 +/- 1,109 mm Hg/s with saline solution, methacholine and oxotremorine, respectively, p < 0.005).
Propranolol was extremely effective against ventricular fibrillation. Methacholine and oxotremorine provided a significant, although less marked, protection and caused much less impairment of contractility compared with propranolol. Muscarinic receptor activation may represent a new approach to prevention of sudden cardiac death, particularly when beta-blockers are contraindicated and negative inotropic effects are to be avoided.
本研究的目的是评估药理学上的毒蕈碱激活的抗纤颤和血流动力学效应，并将其与β-肾上腺素能阻滞的效应进行比较。
最近的研究表明迷走神经活动增加与心脏性猝死发生率降低之间存在相关性。在心脏性猝死的清醒动物模型中，电刺激迷走神经可降低室颤发生率。
对11只患有陈旧性前壁心肌梗死的犬进行研究，在运动期间左回旋支冠状动脉闭塞2分钟会导致室颤。随后它们接受了生理盐水、普萘洛尔（1mg/kg体重）、乙酰甲胆碱（0.5μg/kg每分钟）和氧化震颤素（8μg/kg）的测试。
在生理盐水测试中，100%的犬发生室颤；在普萘洛尔测试中仅10%发生室颤（95%置信区间0.2%至44%；p<0.001），在乙酰甲胆碱测试中60%发生室颤（95%置信区间26%至88%，p = 0.05），在氧化震颤素测试中37.5%发生室颤（95%置信区间8%至75%，p = 0.005）。与生理盐水相比，普萘洛尔和氧化震颤素显著降低心率，而乙酰甲胆碱则没有。与其他治疗相比，普萘洛尔显著降低左心室压力的最大一阶导数（dP/dtmax），尤其是在心肌缺血期间（普萘洛尔组为2391±582mmHg/s[平均值±1标准差]，而生理盐水、乙酰甲胆碱和氧化震颤素组分别为4226±1237、4922±584和4358±1109mmHg/s，p<0.005）。
普萘洛尔对室颤极为有效。乙酰甲胆碱和氧化震颤素提供了显著的保护作用，尽管效果不如普萘洛尔明显，并且与普萘洛尔相比，对收缩力的损害要小得多。毒蕈碱受体激活可能代表了一种预防心脏性猝死的新方法，特别是在β受体阻滞剂禁忌且需要避免负性肌力作用的情况下。
