We hypothesized that the antiarrhythmic efficacy of
propranolol during acute
myocardial ischemia could be dose related.
Propranolol was administered in two equally divided doses 30 min before and 10 min after
ligation of the anterior descending coronary artery (CAL) in anesthetized open-chest pigs. Only the lowest dose of
propranolol, i.e., 0.1 mg/kg intravenously (i.v.) (plasma level 22 +/- 2 ng/ml) decreased the incidence of
ventricular fibrillation (VF), i.e. 3 of 12 versus 16 of 20 in control group (p less than 0.01). VF incidence with
propranolol 0.5 or 3 mg/kg was 4 of 6 and 8 of 9, respectively (both NS vs. control group).
Propranolol 0.1 mg/kg did not change left ventricular (LV) blood flow.
Propranolol 3 mg/kg reduced blood flow in the peripheral ischemic myocardium to 13.2 +/- 1.2 versus 19.2 +/- 1.4 ml/100 g/min in control group (p less than 0.01), and in the midischemic zone to 4.4 +/- 0.5 versus 7.0 +/- 0.9 ml/100 g/min in control group (p less than 0.001).
Propranolol 0.1 mg/kg prevented a disparity of levels of
cyclic AMP from arising between ischemic and non-ischemic myocardium, whereas
propranolol 3.0 mg/kg did not. Furthermore, LV mechanical function was suppressed by
propranolol 3 mg/kg. Only the lowest dose of
propranolol (i.e., 0.1 mg/kg) decreased the incidence of VF in this model.