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Age Dependent Effects on Cisapride Induced QTc Prolongation in the Isolated Guinea Pig Heart
Author(s) -
Adams Nancy,
Spruell Russell,
Mittelstadt Scott
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a320-a
Subject(s) - cisapride , qt interval , guinea pig , medicine , prolongation , adult male , anesthesia , pharmacology
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. Methods 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, & 50 ng/ml) of cisapride were infused for 15 minutes from low to high concentration. Measurements were typically made on 5 consecutive electrocardiogram complexes during the last minute of each concentration. Results Adult guinea pigs had significantly longer RR and QTc intervals when compared to young animals. Cisapride prolonged QTc in both young and adult animals at the same concentrations (5 ng/ml & 50 ng/ml). Discussion In summary, the present study demonstrated that there was an increase in the RR and QTc intervals with age in isolated guinea pig hearts. However, this age difference does not appear to impact the sensitivity of the assay to drug induced QTc prolongation.