Attenuation of the rise in extracellular potassium concentration during myocardial ischaemia by d.l-sotalol and d-sotalol

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Abstract
Study objective – The aim was to study the effects of d.l-sotalol, d-sotalol or atenolol on the rate of rise of extracellular potassium concentration ([K-]o) and the electrophysiological changes that occur during myocardial ischaemia. Design – The study was performed in isolated, arterially perfused interventricular septa from rabbit. Six septa were treated with d.l-sotalol 10−4mol·litre−1, six with d-sotalol 10−4 mol·litre−1, six with atenolol 10−5 mol·litre−1, and there were seven untreated controls. At these concentrations d.l and d-sotalol are equipotent in their class III effect, though d-sotalol has only 7% of the β blocking activity of the racemic form, and atenolol is equipotent in its β blocking activity to d.l-sotalol. [K-]o and electrophysiological variables were compared before and during a 30 min period of global zero flow ischaemia. Measurements and main results – Prior to ischaemia [K-]o, measured using potassium sensitive valinomycin electrodes, was similar in all the groups. [K-]o rose during ischaemia in all the groups, and at 30 min was 13.0 (SEM 0.7) mmol·litre−1 in the control group which was not different from 12.7(0.5) mol·litre−1 in the atenolol group. In the d.l and d-sotalol groups the increases were markedly attenuated, reaching 9.2(1.0) and 8.8(0.7) mmol·litre−1 respectively. During ischaemia the class III effect of d.l and d-sotalol was lost within 6 min though the fall in maximum upstroke velocity of the action potentials (dV/dtmax) and the extent of resting membrane potential (Em) depolarisation were less in comparison to the control and atenolol groups. Conclusions – The results indicate an attenuation by sotalol of the ischaemic rise in [K-]o, with preservation of dV/dtmax and Em, despite the loss of an effect on action potential duration. This potentially antiarrhythmic effect of sotalol in ischaemic myocardium is attributable to a direct membrane effect rather than p adrenoceptor antagonism.