BETA-ADRENERGIC BLOCKING PROPERTY OF DL-SOTALOL MAINTAINS CLASS-III EFFICACY IN GUINEA-PIG VENTRICULAR MUSCLE AFTER ISOPROTERENOL

Background Catecholamines antagonize the efficacy of several class LII antiarrhythmic agents. To determine the role of the intrinsic beta-ad renergic blocking property of dl-sotalol in maintaining class III effi cacy during a high-catecholamine state, we compared the electrophysiol ogical properties of dl-sotalol with those of d-sotalol, which is devo id of significant beta-adrenergic blocking effect, before and after is oproterenol infusion. Methods and Results Action potential duration at 90% repolarization (APD(90)) was prolonged in isolated guinea pig pap illary muscles perfused with d-sotalol and dl-sotalol 10(-4) mol/L ove r stimulation cycle lengths from 200 to 2000 ms. The increases in APD( 90) for d-sotalol and dl-sotalol over control were 10.9+/-2.5 to 23.7/-4.8 ms and 27.9+/-4.0 to 39.0+/-5.6 ms, respectively. APD(90) shorte ned to less than control in papillary muscles treated with d-sotalol b ut not dl-sotalol on addition of isoproterenol 10(-6) mol/L: -31.2+/-3 .5 to -18.3+/-4.8 ms and 10.5+/-3.6 to 33.3+/-7.8 ms, respectively, P< .003. Single guinea pig ventricular myocytes were studied by the whole -cell patch clamp method. Time-dependent (I-out) and total (I-tot) out ward current in response to a 300-ms pulse to 20 mV and tail current ( I-tail) to -35 mV were measured after Ca2+ channel block and Na+ chann el inactivation. I-out, I-tail, and I-tot were reduced in myocytes per fused with d-sotalol and dl-sotalol 10(-4) mol/L: I-out, -36.1+/-4.1%, -40.5+/-3.3%; I-tail, -59.3+/-4.6%, -62.2+/-11.1%; I-tot, -27.3+/-4.3 %, -50.0+/-11.8%. I-out and I-tot increased to a greater degree in myo cytes treated with d-sotalol than dl-sotalol on addition of isoprotere nol 10(-6) mol/L: I-out, 100.3+/-20.6%, 11.3+/-7.6%, P=.002; I-tot, 86 .8+/-39.2%, -41.1+/-20.9%, P=.01. I-tail tended to increase more in my ocytes treated with d-sotalol than dl-sotalol on addition of isoproter enol, but the difference was not significant (-9.1+/-13.5%, -28.0+/-9. 0%). Conclusions The beta-adrenergic blocking property of dl-sotalol m aintains APD prolongation and repolarizing outward current block durin g isoproterenol infusion in guinea pig ventricular muscle. Extrapolati on of these data to a clinical setting may explain the efficacy of dl- sotalol in diminishing ventricular arrhythmia recurrence.