The influence of acute myocardial ischaemia on the Class III antiarrhythmic action of sotalol

The effects of acute myocardial ischaemia on the Class III antiarrhythmic properties of dl-sotalol 10(-4) mol . litre-1 were studied in the isolated arterially perfused interventricular septum of the rabbit heart. Before ischaemia, sotalol increased mean action potential duration (APD90) from 267 +/- 6 to 406 +/- 19 ms (p less than 0.001 mean +/- SEM, n = 7 septa), and mean effective refractory period (ERP) from 222 +/- 7 to 291 +/- 10 ms. During 30 min zero flow global ischaemia, mean APD90 in the control group fell from 264 +/- 7 to 128 +/- 13 ms (n = 7). APD90 fell more rapidly in the sotalol group, so that the initial difference between the sotalol and control groups was abolished after 24 min ischaemia. In the sotalol group, ERP shortened rapidly during ischaemia, and was significantly less than in the control group after 30 min. These changes were associated with the development of substantial post-repolarisation refractoriness in the control but not in the sotalol group. There was a greater fall in action potential upstroke velocity in the controls than in the sotalol group. The results indicate that the Class III effect of sotalol gradually disappears during ischaemia. The effects on post-repolarisation refractoriness and upstroke velocity are compatible with the hypothesis that sotalol slows the rate of rise of extracellular potassium concentration in acute ischaemia. This is a potentially antiarrhythmic property.