Premium
Mechanisms underlying the antiarrhythmic properties of β‐adrenoceptor blockade against ischaemia‐induced arrhythmias in acutely prepared rats
Author(s) -
Paletta M.J.,
Abraham S.,
Beatch G.N.,
Walker M.J.A.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb16866.x
Subject(s) - atenolol , propranolol , blockade , heart rate , medicine , antiarrhythmic agent , coronary occlusion , pharmacology , blood pressure , anesthesia , endocrinology , ischemia , receptor , heart disease
1 The mechanism underlying the limited antiarrhythmic effects of β‐adrenoceptor blocking agents against occlusion‐induced arrhythmias in acutely prepared, pentobarbitone‐anaesthetized rats has been investigated. 2 Atenolol, ICI 111,581 and propranolol were given at low, medium and high doses calculated to shift dose‐response curves to exogenous agonists by factors of 10–30, 100–300 and 1000–3000, respectively. 3 Arrhythmias, blood pressure, heart rate, ECG changes and serum K + were measured. 4 Antiarrhythmic activity was seen with β‐blocker treatment. This was minimal with atenolol (0.1, 1 and l0 mg kg −1 ) and only statistically significant with the highest dose of ICI 111,581 (5 mg kg −1 ), and propranolol (10 mg kg −1 ). 5 Treatment with β‐adrenoceptor blockers elevated serum potassium concentrations, as compared with saline controls, especially when measured at 30 min post‐occlusion. 6 Only ICI 111,581 (5 mg kg −1 ) and propranolol (1 and 10 mg kg −1 ) prolonged P‐R interval. 7 In order to evaluate possible mechanisms of antiarrhythmic action, attempts were made to correlate antiarrhythmic activity with β‐blockade, serum potassium concentrations, and/or with changes in the P‐R interval of the ECG. 8 Reductions in arrhythmias did not correlate well with presumed β‐blockade. Better correlation was obtained with elevations of serum potassium concentration, and with prolongation of P‐R interval (a presumed Class I antiarrhythmic action). 9 These results suggested that antiarrhythmic effects of adrenoceptor blocking agents in acutely‐prepared anaesthetized rats, subjected to occlusion of a coronary artery, are unrelated to cardiac β‐blockade. The limited antiarrhythmic effects which were observed could be attributed to elevations in serum potassium concentration (due to peripheral β‐blockade) and/or possible Class I antiarrhythmic actions.