Intravenous dantrolene does not exhibit calcium channel blocking effects on the cardiac conduction system in humans

Abstract

In malignant hyperthermia, dantrolene, a drug assumed to possess calcium channel blocking properties, effectively suppresses supraventricular and ventricular arrhythmias. To investigate antiarrhythmic properties of dantrolene, six patients (three women and three men, age 42 ± 18 yr) with symptomatic atrioventricular (AV)-nodal reentry tachycardia were studied. Electrocardiographic measurements included sinus cycle length, PQ-interval, width of the QRS-complex, and QT- and rate-corrected QT-interval. During the electrophysiologic study, effective refractory periods of the right atrium, AV node, right ventricle, and AV-nodal conduction intervals were determined, and AV-nodal reentry tachycardia was induced in all patients. Dantrolene was administered intravenously over a period of 15 min at doses of 1.0, 1.5, or 3.0 mg/kg in two patients each. The dosage was not further increased because of side effects at the dose of 3.0 mg/kg. After the infusion of dantrolene, the electrocardiographic measurements and electrophysiologic study were repeated. The plasma concentrations of dantrolene ranged from 1.69 to 6.61 μg/ml at the time of the electrophysiologic study. After dantrolene administration, the sinus cycle length shortened from 686 ± 80 to 622 ± 55 ms (P < 0.05). No significant changes of any other parameter could be demonstrated after intravenous dantrolene. AV-nodal reentry tachycardia remained inducible in all patients without change of the tachycardia cycle length and without change in coupling intervals of tachycardia-inducing extrastimuli. Antiarrhythmic properties of dantrolene could not be demonstrated in patients with AV-nodal reentry tachycardia at therapeutic doses. These results do not give evidence for a direct verapamil-like antiarrhythmic effect of dantrolene in patients with malignant hyperthermia. Suppression of arrhythmias during treatment of MH may be due to other effects of the drug.