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-degrees to 27-degrees-C by means of conventional microelectrode techniques. We also examined the rate-dependent effect of d-sotalol at 37-degrees and 27-degrees-C. Before the addition of d-sotalol, reducing the temperature from 37-degrees to 27-degrees-C increased the action potential duration recorded at 50% repolarization (APD50) from 112 +/- 7 msec to 271 +/- 15 msec and action potential duration recorded at 90% repolarization (APD90) from 136 +/- 7 msec to 325 +/- 10 msec. d-Sotalol (50-mu-mol/L) lengthened APD50 and APD90 to a greater degree at low temperatures. Thus at 37-degrees-C d-sotalol lengthened APD50 and APD90 by 12 +/- 6 msec and 19 +/- 5 msec, and at 27-degrees-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-degrees-C than at 37-degrees-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.