Prevention of postischaemic ventricular fibrillation by long term beta adrenoceptor blockade with acebutolol in the anaesthetised dog

Abstract

Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment underwent the same procedure. Coronary ligations in the randomised study were performed during seven consecutive days, and four dogs were operated on each day. This schedule was chosen in order to measure acebutolol plasma concentrations just before ligation from 60 to 540 min after the last dose of the drug. Long term oral treatment with acebutolol protected against postischaemic ventricular fibrillation and significantly reduced the incidence of both early phase (0-10 min postocclusion) ventricular arrhythmias and ventricular fibrillation. As a result the outcome was significantly improved after 60 min of ischaemia in acebutolol compared with placebo treated animals. The results in the control animals were similar to those in the placebo treated dogs. The protective effect of long term oral treatment with acebutolol lasted for nine hours and was apparently independent of the plasma concentrations of the drug. These data show that improved outcome in this canine model is due to the prevention of ischaemia induced ventricular fibrillation by long term beta adrenoceptor blockade, which is able to overcome the effect, if any, of partial agonist activity of acebutolol. A direct myocardial anti-ischaemic effect might explain the effectiveness of long term oral treatment, which is independent of plasma concentrations of the drug.

Independent sensitization of beta‐adrenoceptors and adenylate cyclase in acute myocardial ischaemia.

“…Clinical observations indicate that only part of these arrhythmias are sensitive to ,3-adrenoceptor blockade (E'Puddu et al, 1986;Menken et al, 1979). As demonstrated here, only part of the alterations of the adenylate cyclase system are ,B-adrenoceptor-coupled.…”

“…This mechanism could protect the endangered myocardial tissue from the deleterious effects of an adrenergic overstimulation (Rona, 1985). However, both clinical (Hjalmerson et al, 1981;Beta-Blocker Heart Attack Trial Research Group 1982) and experimental (Menken et al, 1979) observations of persistent malignant arrhythmias (Corr et al, 1978;Penny, 1984) in acute myocardial infarction which are in part sensitive to ,B-adrenoceptor blockade (E'Puddu et al, 1986) underscore prolonged responsiveness of the 13-adrenergic system in the ischaemic zone. Elevated intracellular cAMP levels in the ischaemic heart (Nokin et al, 1983;Wollenberger et al, 1969) even indicated an activated ,B-adrenergic system.…”

The effects of the propranolol enantiomers on the intracardiac electrophysiological activities of Langendorff perfused hearts

“…Beta adrenergic receptor antagonists are well established agents in the treatment of a great variety of cardiac arrhythmias (7,11,14,17). For different types of arrhythmias and individual IS-receptor blockers, whether the competitive blocking of beta adrenergic receptors and/or a membrane stabilizing effect is responsible for the antiarrhythmic effect (12) remains controversial.…”

Professor André Jouve (1909-2001): A French cardiologist who was a pioneer of clinical vector-electrocardiography and cardiovascular epidemiology

“…QRST complexes in leads: DI, DIII, aVF, V1 and V6, registered at 50 mm/s speed). Then the collaboration was later long lasting and productive [13][14][15][16][17][18][19][20] with his Associate Professor Jean Torresani at INSERM Unit 175 of Experimental Cardiology, Rue Viton, in the beautiful sector of Sainte Marguerite and especially with his son Professor Rémy Jouve (1948Jouve ( -1990) who devoted to Pharmacology and with whom I became very close friend with up to our last efforts, in 1988, on Cardiovascular Epidemiology although starting from electrocardiography [20].…”