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Reduction of repolarization reserve by halothane anaesthesia sensitizes the guinea-pig heart for drug-induced QT interval prolongation.
- Source :
-
British Journal of Pharmacology . Oct2005, Vol. 146 Issue 4, p561-567. 7p. 5 Diagrams. - Publication Year :
- 2005
-
Abstract
- 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.British Journal of Pharmacology (2005) 146, 561–567. doi:10.1038/sj.bjp.0706352; published online 1 August 2005 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 146
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18601858
- Full Text :
- https://doi.org/10.1038/sj.bjp.0706352