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

被引:56
作者
DEFERRARI, GM
SALVATI, P
GROSSONI, M
UKMAR, G
VAGA, L
PATRONO, C
SCHWARTZ, PJ
机构
[1] OSPED POLICLIN, IRCCS, DIV CARDIOL, MILAN, ITALY
[2] LAB CARDIOVASC FARMITALIA CARLO ERBA, MILAN, ITALY
[3] UNIV CHILE, CATTEDRA FARMACOL, SANTIAGO, CHILE
[4] UNIV PAVIA, DIPARTIMENTO MED, I-27100 PAVIA, ITALY
[5] UNIV MILAN, IST CLIN MED 2, VIA F SFORZA 35, I-20122 MILAN, ITALY
关键词
D O I
10.1016/0735-1097(93)90845-R
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:283 / 290
页数:8
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