TY - JOUR
T1 - Pharmacologic 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
AU - De Ferrari, Gaetano M.
AU - Salvati, Patricia
AU - Grossoni, Mauro
AU - Ukmar, Giorgio
AU - Vaga, Lorenzo
AU - Patrono, Carlo
AU - Schwartz, Peter J.
PY - 1993
Y1 - 1993
N2 - 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 beta-adrenergic 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 μg/kg per min) and oxotremorine (8 μg/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 pressare, (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). Conclusions. 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.
AB - 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 beta-adrenergic 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 μg/kg per min) and oxotremorine (8 μg/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 pressare, (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). Conclusions. 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.
UR - http://www.scopus.com/inward/record.url?scp=0027156106&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027156106&partnerID=8YFLogxK
U2 - 10.1016/0735-1097(93)90845-R
DO - 10.1016/0735-1097(93)90845-R
M3 - Article
C2 - 8509552
AN - SCOPUS:0027156106
VL - 22
SP - 283
EP - 290
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 0735-1097
IS - 1
ER -