Assessing QT prolongation in conscious dogs: validation of a beat-to-beat method

Pharmacology & Therapeutics
A A Fossa

Abstract

A model of sling-trained, conscious mongrel dogs instrumented with telemetric arterial pressure transmitters and ECG leads was validated for assessment of the QT-RR interval relationship at clinically used free and total plasma concentrations of positive and negative standards with known outcomes. The beat-to-beat technique for assessing the dynamic boundaries of the individual cardiac cycles was compared to the same data with typically used averaging techniques and corrections applied. Positive standards E-4031, cisapride, terodiline, and terfenadine showed increased sensitivity toward detection at clinically relevant levels when an outlier analysis of beats beyond the normal autonomic boundary is applied. Since methods to correct the QT interval for heart rate are often confounded with changes in autonomic state, a validation of the changes with reflex tachycardia induced by vasodilatation after nitroprusside and reflex bradycardia induced by sudden vasoconstriction with phenylephrine where shown to be differentiated from direct effects of repolarization with E-4031. These changes were also demonstrated to be identical to effects observed in humans after standing or challenged with a similar dose of phenylephrine. The conscio...Continue Reading

References

May 11, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Velislav N BatchvarovMarek Malik
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
Nov 1, 2007·Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc·Anthony A FossaNenad Sarapa

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Citations

Dec 17, 2009·Toxicology and Applied Pharmacology·Nathaniel LeeMichael J Curtis
Jul 2, 2008·Pharmacology & Therapeutics·Michael K PugsleyMichael J Curtis
May 30, 2013·Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc·Christina AbrahamssonGöran Duker
May 1, 2010·Journal of the American College of Cardiology·Wojciech Zareba
Jun 12, 2019·Journal of Receptor and Signal Transduction Research·He-Hsiung ChengChung-Ren Jan
Dec 28, 2019·Journal of Veterinary Cardiology : the Official Journal of the European Society of Veterinary Cardiology·M WibergH Lohi

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