Class III antiarrhythmic action of d-sotalol during hypothermia

To investigate whether changes in temperature influence the electrophysiologic effects of the class III antiarrhythmic agent d-sotalol, we studied its effects on propranolol-pretreated guinea pig papillary muscles at temperatures ranging from 37° to 27° C by means of conventional microelectrode techniques. We also examined the rate-dependent effect of d-sotalol at 37° and 27° C. Before the addition of d-sotalol, reducing the temperature from 37° to 27° C increased the action potential duration recorded at 50% repolarization (APD 50) from 112 ± 7 msec to 271 ± 15 msec and action potential duration recorded at 90% repolarization (APD 90) from 136 ± 7 msec to 325 ± 10 msec. d-Sotalol (50 μmol/L) lengthened APD 50 and APD 90 to a greater degree at low temperatures. Thus at 37° C d-sotalol lengthened APD 50 and APD 90 by 12 ± 6 msec and 19 ± 5 msec, and at 27° C by 37 ± 5 msec and 52 ± 7 msec, respectively. d-Sotalol produced its greatest effect on APD at long pacing cycle lengths, thus demonstrating reverse dependence. This rate-dependent effect was more marked at 27° C than at 37° C. The greater effect of d-sotalol on APD at long pacing cycle lengths may be explained by the modulated receptor hypothesis, assuming that the drug has a higher affinity for closed potassium channels. Such a mechanism may also explain the accentuated class III antiarrhythmic action of d-sotalol observed during hypothermia.