Reduction of repolarization reserve by halothane anaesthesia sensitizes the guinea-pig heart for drug-induced QT interval prolongation

摘要

class="enumerated" style="list-style-type:decimal">The utility of halothane-anaesthetized guinea-pigs as an in vivo model for predicting the clinical potential of a drug to induce QT interval prolongation was assessed using the electrocardiogram and monophasic action potential (MAP) recordings with electrical ventricular pacing.Intravenous administration of D-sotalol (0.3 mg kg⁻¹) and terfenadine (0.3 mg kg⁻¹), blockers of a rapid component of delayed rectifier potassium currents, prolonged the QT interval by 32±7 and 23±6 ms, respectively, whereas chromanol 293B (1 mg kg⁻¹), a blocker of a slow component of delayed rectifier potassium currents, lengthened it by 33±8 ms. The extent of the QT interval prolongation by these drugs was greater than those in previous reports using pentobarbital-anaesthetized guinea-pigs.The MAP duration at the control was shortened by decreasing the pacing cycle length from 400 to 200 ms, but the MAP duration at each cycle length was prolonged by D-sotalol.The formulas of Van de Water, Matsunaga, Fridericia and Bazett showed good correlation of the repolarization period when compared with the MAP duration at a pacing cycle length of 400 ms.The halothane-anaesthetized guinea-pig model may possess enough sensitivity to detect drug-induced QT interval prolongation, indicating that halothane anaesthesia can reduce the repolarization reserve of the heart in vivo.