Methodological validation of an existing telemetry system for QT evaluation in conscious guinea pigs.
BACKGROUND
Guinea pigs are suitable for in vivo QT assessment of newly discovered drugs at the pre-clinical stage because of the ease with which these animals can be handled, the lower amount of compound required for testing, and the similarity of the ion channels between the guinea pig heart and the human. Our purpose was to provide detailed methodological information on an existing telemetry recording system for use in evaluating QT interval prolongation in guinea pigs.


METHODS
Hartley guinea pigs weighing 400-700 g were used to investigate the appropriate configuration of electrodes to record defined T-waves and the influence of the surgical implantation of a transmitter on the QT interval, as well as to determine the appropriate formula for QT correction. In addition, the validity of using telemetry-monitored guinea pigs was tested by using compounds with (positive references) or without (vehicles) a QT-prolonging effect.


RESULTS
A lead with the negative pole placed between the scapulas and the positive pole positioned close to the sternum was found to be the most appropriate to obtain well-defined T-waves. The period for recovery from transmitter implantation was estimated to be at least 1 week. The best-fit formula for our telemetry guinea pig model was a modified Bazett's formula. QTc was prolonged significantly in guinea pigs given positive references, and the QTc was unaffected when the animals were given vehicles.


CONCLUSIONS
We believe that the information provided herein will be a quite helpful guide for researchers to evaluate the QT interval reliably and reproducibly in this telemetry guinea pig model.
Shiotani
Motohiro
M
Worldwide Safety Sciences, Pfizer Global Research and Development, Nagoya Laboratories, Pfizer Japan Inc. 5-2 Taketoyo, Aichi 470-2393, Japan. motohiro.shiotani@pfizer.com
Harada
Takuma
T
Abe
Junko
J
Hamada
Yoshimasa
Y
Horii
Ikuo
I
D000818:Animals; D016589:Astemizole / Q000494:pharmacology; D004562:Electrocardiography / Q000295:instrumentation / Q000379:methods*; D004567:Electrodes, Implanted; D006168:Guinea Pigs; D008133:Long QT Syndrome / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D013015:Sotalol / Q000494:pharmacology; D013686:Telemetry / Q000379:methods*
D016589:Astemizole; D013015:Sotalol