Age-dependent effects on cisapride-induced QTc prolongation in the isolated guinea pig heart

Journal of Pharmacological and Toxicological Methods
Scott MittelstadtR D Spruell

Abstract

The isolated guinea pig heart preparation has been suggested as a suitable small animal model for investigating potential for QTc prolongation. The purpose of this study was to investigate the effect of age on electrophysiological parameters measured in the isolated guinea pig heart preparation. In addition, the effect of a compound known to prolong the QT interval (cisapride) was investigated in both young and adult guinea pigs. Male guinea pigs were divided into 2 groups (n=6). One group of guinea pigs was between 3 and 4 weeks old (young) and the other group was between 16 and 17 weeks old (adult). Concentrations (0, 1, 5, and 50 ng/mL; 2, 11, and 110 nM) of cisapride were perfused for 15 min from low to high concentration. Measurements of PR, QRS, RR and QT intervals were typically made on 5 consecutive electrocardiogram complexes during the last minute of each concentration. The QT interval was corrected for changes in heart rate using the cube root formula of Fridericia (QTcF). Adult guinea pigs had significantly longer RR and QTcF intervals when compared to young animals. Cisapride prolonged QTcF in both young and adult animals at the same concentrations (5 ng/mL and 50 ng/mL). The maximal change in QTcF at 50 ng/mL was ...Continue Reading

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Citations

Sep 25, 2007·Journal of Pharmacological and Toxicological Methods·Motohiro ShiotaniIkuo Horii
Dec 25, 2007·Experimental Physiology·Frank C HowarthErnest Adeghate
Jun 30, 2006·Journal of Pharmacological and Toxicological Methods·Michael K Pugsley, Michael J Curtis
Jul 18, 2006·Journal of Pharmacological and Toxicological Methods·R L Hamlin
Jun 13, 2012·The Journal of Toxicological Sciences·Anusak KijtawornratRobert L Hamlin
Dec 27, 2016·Clinical and Experimental Pharmacology & Physiology·Kamalan JeevaratnamChristopher L-H Huang
Jun 26, 2008·Digestion·Yuko MishimaYoshikazu Kinoshita

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