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
References
Jan 1, 1995·Journal of Cardiovascular Pharmacology·S P PinneyR L Woosley
Jul 1, 1993·The Journal of Surgical Research·J W HortonL Mahony
Dec 1, 1996·Clinical Cardiology·M Reardon, M Malik
Dec 22, 1999·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·A J Moss
Mar 3, 2001·Pacing and Clinical Electrophysiology : PACE·T TanejaA Kadish
Aug 11, 2001·European Journal of Clinical Pharmacology·F De PontiN Montanaro
Feb 22, 2003·Pediatric Research·Mei-Hwan WuSelma Siu-Man Sun
Apr 2, 2003·Cardiovascular Research·W S RedfernT G Hammond
May 2, 2003·Age and Ageing·Arduino A MangoniStephen H D Jackson
Aug 12, 2003·Cardiovascular Research·Maria N ObreztchikovaMichael R Rosen
Dec 13, 2003·Journal of Pharmacological and Toxicological Methods·R L HamlinT Arnold
Jun 3, 2004·Journal of Pharmacological and Toxicological Methods·Alan BassPatricia Williams
Aug 17, 2004·The Journal of Physiology·Sandra A JonesMark R Boyett
Jun 4, 2005·Journal of Pharmacological and Toxicological Methods·Brian M RocheDavid M Hamlin
Jun 22, 2005·Journal of Pharmacological and Toxicological Methods·Alan S BassLewis B Kinter
Citations
Sep 25, 2007·Journal of Pharmacological and Toxicological Methods·Motohiro ShiotaniIkuo Horii
Dec 25, 2007·Experimental Physiology·Frank C HowarthErnest Adeghate
Feb 1, 2007·Journal of Applied Toxicology : JAT·L TestaiV Calderone
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