PHARMACOLOGICAL MODULATION OF THE AUTONOMIC NERVOUS-SYSTEM IN THE PREVENTION OF SUDDEN CARDIAC DEATH - A STUDY WITH PROPRANOLOL, METHACHOLINE AND OXOTREMORINE IN CONSCIOUS DOGS WITH A HEALED MYOCARDIAL-INFARCTION
PHARMACOLOGICAL MODULATION OF THE AUTONOMIC NERVOUS-SYSTEM IN THE PREVENTION OF SUDDEN CARDIAC DEATH - A STUDY WITH PROPRANOLOL, METHACHOLINE AND OXOTREMORINE IN CONSCIOUS DOGS WITH A HEALED MYOCARDIAL-INFARCTION
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DOI：
10.1016/0735-1097(93)90845-r
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发表时间：
1993-07-01
影响因子：
24
通讯作者：
SCHWARTZ, PJ
中科院分区：
文献类型：
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作者：
DEFERRARI, GM;SALVATI, P;SCHWARTZ, PJ
目标.本研究的目的是评价药理学毒蕈碱激活的抗惊厥和血流动力学作用，并将其与β肾上腺素能阻滞剂的作用进行比较。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。迷走神经电刺激可降低心脏性猝死清醒动物模型心室颤动的发生率。对11只前壁心肌梗死犬进行了研究，其中在运动过程中左回旋支冠状动脉闭塞2分钟引起心室颤动。他们随后接受了生理盐水，普萘洛尔（1毫克/公斤体重），乙酰甲胆碱（每分钟0.5微克/公斤）和氧化震颤素（8微克/公斤）的测试。在用生理盐水进行的试验中，100%的狗出现心室纤颤;而在用心得安进行的试验中，只有10%的狗出现心室纤颤（95%置信区间0.2%~ 44%; p < 0.001），60%的乙酰甲胆碱试验（95%置信区间26%至88%，p = 0.05）和37.5%的氧化震颤素试验（95%置信区间8%至75%，p = 0.005）。普萘洛尔和oxotremorine显着降低心率与生理盐水相比，而乙酰甲胆碱没有。普萘洛尔显著降低左心室压力的最大一阶导数，（dP/dt（max）），特别是在心肌缺血期间，与其他治疗相比（普萘洛尔组为2，391 +/- 582 mm Hg/s [平均值+/- 1 SD]，生理盐水、乙酰甲胆碱和氧震颤素组分别为4，226 +/-1，237、4，922 +/- 584和4，358 +/-1，109 mm Hg/s，p < 0.005）。普萘洛尔对室颤非常有效。乙酰甲胆碱和oxotremorine提供了一个显着的，虽然不太明显，保护和造成的损害少得多的收缩力与普萘洛尔相比。毒蕈碱受体激活可能是预防心脏性猝死的一种新方法，特别是当β受体阻滞剂是禁忌和负性肌力作用是要避免的。
Objectives. 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 betaadrenergic blockade.Background. 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.Methods. 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 mug/kg per min) and oxotremorine (8 mug/kg).Results. 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/dt(max)), 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).Conclusions. Propranoiol 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.