Pharmacologic response of cesium-induced ventricular tachyarrhythmias in anesthetized dogs.
Cesium chloride administration causes ventricular tachyarrhythmias in dogs, with many of the features of the clinical long QT syndrome. We developed a model of cesium-induced arrhythmias, using loading and maintenance doses of cesium to produce continuous cesium effects. The purpose of the present experiments was to study the response of arrhythmias in this model to a variety of pharmacologic interventions. Cesium chloride caused ventricular tachyarrhythmias that either degenerated to ventricular fibrillation (VF) or remained stable for greater than 30 min. Cesium-induced arrhythmias were suppressed by the calcium antagonist diltiazem, magnesium chloride, beta blockade (with atenolol), or vagal nerve stimulation--all interventions that can suppress calcium entry. beta-Adrenergic stimulation with isoproterenol initiated ventricular arrhythmias in the presence of subarrhythmic doses of cesium. Sodium channel blockers (lidocaine and high concentrations of quinidine) also suppressed cesium-induced arrhythmias. Intravenous (i.v.) bolus doses of isotonic saline solution at times corresponding to the other interventions studied did not alter the severity of cesium-induced arrhythmia. We conclude that cesium-induced ventricular arrhythmias in this model are suppressed by agents that reduce transmembrane calcium currents as well as by high doses of sodium channel blockers. These findings may have relevance to the mechanisms of, and the therapeutic approach to, the clinical long QT syndrome.
Department of Medicine, Montreal Heart Institute, Canada.
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Nayebpour
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Nattel
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D002586:Cesium; D002712:Chlorides; D002851:Chromatography, High Pressure Liquid; D004110:Diltiazem / Q000097:blood / Q000627:therapeutic use*; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology; D008012:Lidocaine / Q000097:blood / Q000627:therapeutic use*; D015636:Magnesium Chloride / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D011802:Quinidine / Q000097:blood / Q000627:therapeutic use*; D015222:Sodium Channels / Q000187:drug effects; D014630:Vagus Nerve
D002712:Chlorides; D015222:Sodium Channels; D015636:Magnesium Chloride; D002586:Cesium; D008012:Lidocaine; D004110:Diltiazem; C028019:cesium chloride; D011802:Quinidine; D007545:Isoproterenol