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There has been increased interest in class III antiarrhythmic drugs for con-version of atrial fibrillation to sinus rhythm. Ambasilide, a class III antiarrhythmic, has been shown to block multiple cardiac channels in a variety of animals including humans. Although the electrophysiological effects of ambasilide are characterized on the cellular level, its effects on an organ level have yet to be investigated. We investigated escalating doses of ambasilide in isolated, per-fused guinea pig hearts. Ambasilide prolonged the RR, PQ, QRS, QT, and QTc (F) in a concentration-dependent manner in either normal sinus rhythm or with reduced heart rate (atriectomy). dP/dtmin was increased (became less negative) in the presence of increasing concentrations of ambasilide, whereas the vehicle produced less negative lusitropy. Ambasilide demonstrated use dependence by prolonging QTc (F) less at slower heart rates. Ambasilide also inhibited isoproterenol-induced tachycardia, suggesting it exerts beta-adrenergic blocking properties. In conclusion, this study suggests that ambasilide has multichannel blocking properties including beta-adrenergic antagonism.

There has been a resurgence in the use of thalidomide over the past several years; however, little is known about its potential cardiac toxicity. Isolated, perfused guinea pig hearts were exposed to escalating concentrations of thalidomide or vehicle, and changes in RR interval, QT duration and QTc duration, and left ventricular inotropy and lusitropy comparing escalating concentrations of thalidomide with vehicle were sought. RR interval lengthened and QTc prolonged significantly at 10 microM concentrations. QT did not change. dP/dtmax increased and dP/dtmin decreased in response to thalidomide. Based on results using this preparation, thalidomide has a potential liability for lengthening QTc, but only at concentrations of 10 microM or greater. It possesses both positive inotropic and positive lusitropic properties.

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