Electrophysiologic effects of procainamide, mexiletine, and amiodarone on the transplanted heart. Experimental study

The effects of procainamide, mexiletine, and amiodarone on automaticity, conduction, and refractoriness were studied in a model of heterotopic heart transplantation in dogs that combined an innervated heart (recipient) and a denervated transplanted heart (donor). After the surgical procedure, 500 mg procainamide (n = 13), 200 mg plus 0.1 mg/kg per minute mexiletine (n = 10), or 150 mg amiodarone (n = 10) was administered intravenously. During a baseline period and after drug administration, each heart was assessed for atrioventricular interval; cycle length; sinoatrial conduction time; atrioventricular node anterograde and retrograde block points; atrioventricular node and ventricular antegrade effective refractory periods; PR, QRS, and QT intervals on electrocardiogram; systemic arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures; and cardiac output. In recipients, procainamide reduced cardiac output, depressed sinus automaticity, slowed conduction time without affecting the QRS interval, and prolonged the nodal and ventricular refractoriness; in donor hearts, it depressed automaticity and prolonged nodal refractoriness, but did not modify conduction or ventricular refractoriness. Mexiletine only moderately depressed sinus automaticity in recipient hearts; it did not affect the other parameters either in recipient or transplanted hearts, nor did it alter the hemodynamic situation. Amiodarone produced hypotension, reduced cardiac output, and prolonged all the electrophysiologic intervals except the QRS interval in recipient hearts. These changes were even more pronounced in the transplanted hearts and led to extreme sinus bradycardia in four cases. Of these three drugs, mexiletine appears to be the safest should treatment for arrhythmias be necessary in transplant recipients.