Class III antiarrhythmic action linked with positive inotropy: effects of the d- and l-isomer of sotalol on isolated rat atria at threshold and suprathreshold stimulation.
The beta-adrenoceptor blocker sotalol has been shown to possess class III antiarrhythmic action. The present study was designed to test the hypothesis that class III antiarrhythmic action and positive inotropy may be linked. Since d,l-sotalol has previously been reported to have variable inotropic effect, we studied direct effects of the d- and l-stereoisomer of sotalol on refractoriness and inotropy of isolated rat atria at different strengths of electrical stimulation. Both the d- and l-stereoisomer of sotalol (7.5 x 10(-5) M) increased the effective refractory period, and to the same extent. However, d-sotalol increased isometric contractile force by 10%, while l-sotalol had no significant effect, when the atria were stimulated at close to threshold values (10 +/- 1 mA). Probably due to release of noradrenaline within the myocardium, contractile force increased when the atria were stimulated at suprathreshold values (40 mA). At suprathreshold stimulation, however, d-sotalol induced a 10% decrease and l-sotalol a 20% decrease, in contractile force. In conclusion, the class III antiarrhythmic action of sotalol is linked with positive inotropy. In the presence of neurotransmitter release, negative inotropic effect of d- and in particular l-sotalol, may occur due to beta-adrenoceptor blocking activity.
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PM
Institute of Medical Biology, University of Tromsø, Norway.
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002316:Cardiotonic Agents; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism; D013268:Stimulation, Chemical
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D013015:Sotalol