Mechanisms underlying the antiarrhythmic properties of beta-adrenoceptor blockade against ischaemia-induced arrhythmias in acutely prepared rats.

1. The mechanism underlying the limited antiarrhythmic effects of beta-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 beta-blocker treatment. This was minimal with atenolol (0.1, 1 and 10 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 beta-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 beta-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 beta-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 beta-blockade. The limited antiarrhythmic effects which were observed could be attributed to elevations in serum potassium concentration (due to peripheral beta-blockade) and/or possible Class I antiarrhythmic actions.