Ischemia-induced action potential shortening is blunted by d-sotalol in a pig model of reversible myocardial ischemia

The purpose of this study was to investigate, in an anesthetized pig model of low-flow myocardial ischemia, the electrophysiologic effects of the clas s III drug d-sotalol during myocardial ischemia. Serial monophasic action p otential (MAPD(90)) recordings and refractory period determinations from th e anterior and posterior left ventricular wall were taken in 25 pigs during baseline, after low-flow posterior wall ischemia, after d-sotalol infusion under nonischemic conditions, and after repeated posterior wall ischemia w hile continuing the drug. Measurements were done at 60 and 150 beats/min af ter radiofrequency ablation of atrioventricular conduction. At baseline, MA PD(90) and refractory periods were comparable in the anterior and posterior wall (323 +/- 15 vs. 318 +/- 10 ms, and 267 +/- 10 vs. 262 +/- 11 ms at 60 beats/min, respectively). In the absence of d-sotalol, low-flow regional i schemia was associated with a significant shortening of MAPD(90) in the pos terior versus the anterior wall (267 +/- 20 vs. 317 +/- 20 ms at 60 beats/m in; p = 0.006). Similarly, ischemia-induced shortening of the refractory pe riods in the posterior wall was apparent (230 +/- 16 ms in the posterior wa ll vs. 274 +/- 14 ms in the anterior wall at 60 beats/min). In contrast, is chemia was no longer associated with shortening of MAPD(90) (360 +/- 17 ms posterior wall and 360 +/- 20 ms anterior wall at 60 beats/min) and refract ory periods (304 +/- 19 ms posterior wall vs. 316 +/- 15 ms anterior wall a t 60 beats/min) during combined posterior wall ischemia and d-sotalol infus ion. Similar findings were obtained during pacing at 150 beats/min. d-Sotal ol attenuates ischemia-induced action potential shortening. This property s hould decrease dispersion of cardiac repolarization and be antiarrhythmic. On the other hand, longer APD under ischemic conditions may favor calcium o verload, which may trigger new arrhythmias.