Early and delayed afterdepolarizations associated with cesium chloride-induced arrhythmias in the dog.
Monophasic action potentials (MAPs) were utilized to examine the basis for cesium-induced arrhythmia in the dog. Cesium chloride (1 mmol/kg i.v.) produced an immediate prolongation of MAP (250 +/- 11 to 396 +/- 34 ms, p less than 0.05). Coupled premature ventricular beats (345 +/- 46 ms) and polymorphic ventricular tachycardia developed in association with early afterdepolarizations during the first 1-3 min after cesium administration. A slowing of the sinus heart rate with vagus nerve stimulation exacerbated the arrhythmia. During the subsequent 7 min, the MAP duration decreased from 396 +/- 34 to 316 +/- 19 ms. At 8-10 min, the premature ventricular beats were associated with delayed afterdepolarizations in the MAP recordings. However, there was no change in the coupling intervals of the premature ventricular beats (351 +/- 29 ms). Ventricular arrhythmias and delayed afterdepolarizations during this phase were exacerbated by increasing the heart rate with atrial pacing. T wave alternans and U wave formation in the ECG were associated with early or delayed afterdepolarizations in MAP. Cesium chloride (1 mmol) injected into the left anterior descending coronary artery produced local MAP prolongation and ventricular bigeminy. Although the MAP duration returned to predrug values after intracoronary cesium injection, the severity of ventricular arrhythmia increased with succeeding doses. These data suggest that early and delayed afterdepolarizations, T wave alterations, and ventricular beats can be dissociated from the initial action potential prolongation with cesium and closely resemble altered calcium transients observed in vitro.
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City.
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E
Patterson
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Szabo
B J
BJ
Scherlag
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Lazzara
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002586:Cesium / Q000633:toxicity; D002712:Chlorides; D003331:Coronary Vessels; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007269:Injections, Intra-Arterial; D008297:Male; D008839:Microelectrodes; D009467:Neuromuscular Depolarizing Agents
D002712:Chlorides; D009467:Neuromuscular Depolarizing Agents; D002586:Cesium; C028019:cesium chloride; D002118:Calcium