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 mumol/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.
Bjørnstad
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Department of Medical Physiology, University of Tromsø, Norway.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D007036:Hypothermia, Induced; D008564:Membrane Potentials / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D013015:Sotalol