Effect of magnesium sulfate on the haloperidol-induced QT prolongation assessed in the canine in vivo model under the monitoring of monophasic action potential.
Haloperidol has been reported to induce polymorphic ventricular arrhythmias associated with QT prolongation. The present study examined the effects of magnesium sulfate on the cardiovascular system suffering from haloperidol overdose. Beagle dogs were anesthetized with halothane inhalation under the monitoring of monophasic action potential (n=6). After intravenous administration of an intentionally high dose of haloperidol (3 mg/kg), the heart rate (HR), left ventricular contraction and mean blood pressure (BP) decreased, and the ventricular repolarization phase and effective refractory period (ERP) were prolonged, the increment in the former being than in the latter, indicating an increase in electrical vulnerability. However, preload of the left ventricle, cardiac output (CO) and cardiac conduction were hardly affected. An additional intravenous dose of 100 mg/kg of magnesium sulfate increased the preload of the left ventricle, and decreased the HR, mean BP, left ventricular contraction and CO, suppressed atrioventricular as well as intraventricular conduction, and prolonged the ventricular repolarization phase and ERP, in which the increment of the repolarization phase was similar to that of ERP. These results suggest that magnesium sulfate hardly affects the electrical vulnerability of the heart during haloperidol overdose, but may block the calcium, potassium and sodium channels, which may explain its antiarrhythmic action.
Satoh
Y
Y
Second Department of Internal Medicine, Yamanashi Medical University, Japan.
Sugiyama
A
A
Tamura
K
K
Hashimoto
K
K
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D018492:Dopamine Antagonists / Q000009:adverse effects*; D006220:Haloperidol / Q000009:adverse effects*; D008133:Long QT Syndrome / Q000139:chemically induced; D008278:Magnesium Sulfate / Q000494:pharmacology* / Q000627:therapeutic use; D017180:Tachycardia, Ventricular / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D018492:Dopamine Antagonists; D008278:Magnesium Sulfate; D006220:Haloperidol