title: Cardiovascular and metabolic effects of caesium chloride injection in dogs--limitations as a model for the long QT syndrome.
abstract: Caesium chloride administration has been used in an animal model to reproduce the acquired long QT syndrome observed in man, but the transient nature of the arrhythmogenic action of caesium has made systematic study difficult. We developed a loading and maintenance infusion regimen to produce stable caesium effects for over 30 min. The results of sustained caesium administration were compared to those of bolus dose caesium and found to be similar in terms of changes in metabolic, electrophysiological, and haemodynamic variables, and the nature of resulting ventricular arrhythmias. Caesium administration by either method consistently induced ventricular tachyarrhythmias that were either monoform or polymorphic, rarely had the morphological features of Torsades de Pointes, and frequently degenerated to ventricular fibrillation. Both forms of caesium administration produced substantial increases in arterial pressure [from 131(SEM12)/63(SEM8) to 246(30)/138(20) mm Hg with sustained infusion; from 120(8)/55(2) to 263(19)/178(16) mm Hg with bolus caesium; p less than 0.01 for each] and serum potassium concentration [from 3.6(0.2) to 8.6(0.8) mmol.litre-1, and from 3.2(0.1) to 7.8(0.7) mmol.litre-1 respectively; p less than 0.01 for each]. Ventricular overdrive pacing transiently accelerated the spontaneous arrhythmia in 48/60 (80%) trials, with overdrive suppression occurring in only five trials. The morphological features of these caesium induced ventricular tachyarrhythmias, their response to overdrive pacing, and their occurrence despite substantial hyperkalaemia are quite different from the properties of the clinical long QT syndrome, which is overdrive suppressible, favoured by hypokalaemia, and rarely degenerates to ventricular fibrillation. We conclude that stable ventricular tachyarrhythmias can be produced by loading and maintenance infusions of caesium in dogs and that the effects of sustained caesium infusion are similar to those of bolus dose caesium, but that caution is necessary in using caesium administration as a model for the clinical long QT syndrome.
authors.affiliation: Department of Pharmacology, McGill University, Montreal, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Nayebpour
authors.forename: B C
authors.initials: BC
authors.lastname: Solymoss
authors.forename: S
authors.initials: S
authors.lastname: Nattel
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002586:Cesium / Q000097:blood / Q000633:toxicity*; D002712:Chlorides / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006352:Heart Ventricles; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D011188:Potassium / Q000097:blood; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000139:chemically induced
chemical_list: D002712:Chlorides; D002586:Cesium; C028019:cesium chloride; D011188:Potassium