Isolated perfused and paced guinea pig heart to test for drug-induced changes of the QT interval

Journal of Pharmacological and Toxicological Methods
Hsien C ChengBruce McCullough

Abstract

One of the biomarkers for assessing the risk of a cardiac adverse event is drug-induced prolongation of the QT interval. A model is needed for evaluating the potential liability of test compounds on QT interval in vitro. Since QT intervals can be generated from paced or spontaneously beating hearts, data so generated can also be used for validating QT(c) correction equations. Isolated guinea pig hearts were perfused in Locke's solution according to the Langendorff method. QT intervals were routinely measured from Lead II ECG waveforms. Compounds known to inhibit HERG channel, such as dofetilide, prolonged the QT interval in this model. (+/-)Bay K8644, a calcium channel activator, prolonged the QT interval, while verapamil, a calcium channel blocker, shortened it. Procainamide, a sodium channel blocker, also prolonged the QT interval. Many of the compounds, which prolonged the QT interval, also prolonged PR interval, suggesting dual inhibition of the Ikr channel, the rapid component of delayed rectifier potassium channel, and the calcium channel. The QT/RR intervals exhibited a curvilinear relationship, which could be corrected into nearly straight horizontal lines by using correction equations derived from linear, parabolic, an...Continue Reading

References

Nov 1, 1989·Journal of Pharmacological Methods·A Van de WaterR S Reneman
Apr 25, 1986·The American Journal of Medicine·R H Helfant
Mar 1, 1995·Journal of the American College of Cardiology·M ZabelM R Franz
Oct 24, 1996·European Journal of Pharmacology·K ItoK Inoue
May 5, 1998·Journal of Pharmacological and Toxicological Methods·T MatsunagaY Shibutani
Oct 24, 2000·The American Journal of Emergency Medicine·A MattuD A Robinson
Jul 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Anthony A FossaDerek J Leishman
Aug 8, 2002·Journal of Pharmacological and Toxicological Methods·D RaunigA A Fossa
Aug 15, 2002·European Journal of Pharmacology·Sathapana KongsamutDavid Rampe
Oct 3, 2002·The Journal of General Physiology·Franklin M MullinsJeffrey R Balser
Jan 10, 2003·Circulation Journal : Official Journal of the Japanese Circulation Society·Tsutomu ArakiMasami Shimizu
May 17, 2003·Journal of Pharmacological and Toxicological Methods·Patrick Davey
May 17, 2003·Journal of Pharmacological and Toxicological Methods·Andrew J Batey, Christopher P A Doe
Jun 14, 2003·Biochemical and Biophysical Research Communications·John M RidleyJules C Hancox
Nov 6, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·Robert L HamlinDavid M Hamlin
Nov 19, 2003·American Journal of Therapeutics·Luigi X Cubeddu
Dec 4, 2003·Biological & Pharmaceutical Bulletin·Hiroshi MizunoWilliam David Kerns
Dec 13, 2003·Journal of Pharmacological and Toxicological Methods·R L HamlinT Arnold
Apr 7, 2004·Journal of Biomedical Science·Chern-En ChiangHsiang-Ning Luk
Jun 12, 2004·Cardiology in Review·Chern-En Chiang
Nov 18, 2004·Pacing and Clinical Electrophysiology : PACE·Rob SandersN Bari Olivier
Jan 18, 2005·Journal of Cardiovascular Pharmacology·Tom A KuuselaTimo J Kaila
Feb 26, 2005·Clinical and Experimental Pharmacology & Physiology·Kiyoshi MatsumuraMitsuo Iida

❮ Previous
Next ❯

Citations

Nov 6, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Anusak KijtawornratRobert L Hamlin
Feb 2, 2010·Journal of Pharmacological and Toxicological Methods·Michel RocheJean-Michel Guillon
Aug 14, 2008·Basic & Clinical Pharmacology & Toxicology·Yasue SakaguchiAtsushi Sugiyama
Sep 18, 2013·European Journal of Pharmacology·Jing MengYanfang Xu
Jun 16, 2009·Journal of Pharmacological and Toxicological Methods·Hsien C Cheng, Josephine Incardona
Jul 21, 2009·Journal of Pharmacological and Toxicological Methods·Liang GuoHeather Guthrie
Dec 27, 2011·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Kazuto YamazakiKohei Sawada
May 22, 2013·Journal of Pharmacological and Toxicological Methods·Henry HolzgrefeMuriel Saulnier
Apr 18, 2013·PloS One·Jeonghyeon ParkYoung-Ran Yoon
Aug 11, 2018·Journal of Cardiovascular Pharmacology and Therapeutics·Bo QiuYanfang Xu
Jan 6, 2011·The Journal of Pharmacology and Experimental Therapeutics·Yusheng QuHugo M Vargas
May 21, 2010·The Journal of Pharmacology and Experimental Therapeutics·Jiesheng KangDavid Rampe
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hongxue ZhangYanfang Xu
Jun 29, 2007·Drugs in R&D·Gilles Hanton

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Anti-Arrhythmic Drug Therapies

Anti-arrhythmic drugs are used to prevent abnormal heart rhythms. These medications are used in conditions including, ventricular tachycardia, ventricular fibrillation and atrial fibrillation. Discover the latest research on anti-arrhythmic drug therapies here.