Mechanisms underlying the antiarrhythmic properties of β‐adrenoceptor blockade against ischaemia‐induced arrhythmias in acutely prepared rats

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Abstract
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. 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. Arrhythmias, blood pressure, heart rate, ECG changes and serum K+ were measured. 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). Treatment with β‐adrenoceptor blockers elevated serum potassium concentrations, as compared with saline controls, especially when measured at 30 min post‐occlusion. Only ICI 111,581 (5 mg kg−1) and propranolol (1 and 10 mg kg−1) prolonged P‐R interval. 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. 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). 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.