EFFECTS OF VERAPAMIL AND PROPRANOLOL ON EARLY AFTERDEPOLARIZATIONS AND VENTRICULAR ARRHYTHMIAS INDUCED BY EPINEPHRINE IN CONGENITAL LONG QTSYNDROME

Objectives. This study used monophasic action potentials to investigat e the effects of verapamil and propranolol on epinephrine-induced repo larization abnormalities in congenital long QT syndrome. Background. E arly afterdepolarizations have been suggested to play a significant ro ;le in QT prolongation and ventricular arrhythmias in congenital long QT syndrome. Calcium channel blocking as well as beta-adrenergic block ing agents are reported to be effective in the management of this synd rome. Methods. Monophasic action potentials from 2 to 4 sites were rec orded simultaneously in eight patients with the long QT syndrome (22 s ites) and in eight control patients (23 sites) and were obtained durin g constant atrial pacing 1) before epinephrine infusion; 2) during epi nephrine infusion (0.1 mu g/kg body weight min); 3) after verapamil in jection (0.1 mg/kg) during epinephrine infusion; and 4) after both pro pranolol (0.1 mg/kg) and verapamil injections. Results. Early afterdep olarizations were recorded in two of the eight patients (2 of 22 sites ) during the control state. During epinephrine infusion, early afterde polarizations were recorded in six patients (six sites),and ventricula r premature complexes were induced in three and torsade de pointes in one. Epinephrine prolonged 90% monophasic action potential duration fr om 348 +/- 48 (mean +/- SD) to 381 +/- 49 ms (22 sites, p < 0.0005) an d increased the dispersion of action potential duration (difference be tween the longest and shortest action potential duration) from 36 +/- 20 to 64 +/- 34 ms (p < 0.005). Verapamil eliminated (two sites) or re duced (four sites) early afterdepolarizations and abolished ventricula r premature complexes in two oi the three patients as well as suppress ing torsade de pointes. Verapamil shortened the action potential durat ion to 355 +/- 28 ms (p < 0.01 vs. epinephrine) and decreased the disp ersion to 44 +/- 19 ms (p < 0.05 vs. epinephrine). Propranolol further eliminated (two sites) or reduced (two sites) early afterdepolarizati ons, abolished ventricular premature complexes in the remaining one pa tient and further Shortened the action potential duration to 337 +/- 3 2 ms (p = 0.09 vs. verapamil). In the control patients, none of the ea rly afterdepolarizations, ventricular arrhythmias or marked prolongati ons of action potential duration mere induced by epinephrine, and neit her verapamil nor propranolol changed repolarization variables. Conclu sions. These results indicate that both verapamil and propranolol can improve repolarization abnormalities induced by epinephrine in congeni tal long QT syndrome.