Development of a surgical approach for telemetering guinea pigs as a model for screening QT interval effects.

INTRODUCTION

Identifying a compound's risk of potentially producing Torsade de Pointes (TdP)/QT interval prolongation has become a goal early within the drug development process. Our aim was to develop a surgical approach for instrumenting guinea pigs for collecting ECG data.

METHODS

Male Dunkin Hartley guinea pigs (386-661 g) were surgically implanted with telemetry transducers for the measurement of lead II ECG and arterial blood pressure. Using strict aseptic techniques and isofluorane anaesthesia (0.5-5.0%), one of the three implantation procedures was used. In Phase I the animals were either implanted intraperitoneally (abdominal aorta cannulated) or subcutaneously (carotid artery cannulated). In Phase II all animals were implanted subcutaneously and the subcutaneous pocket formed either with a single incision, as in Phase I, or a double incision.

RESULTS

Phase I-During intraperitoneal implantation, rupture of the aorta occurred in 50% of the animals. The remaining animals were terminated between 2 and 14 days postsurgery on human grounds. All of the animals implanted subcutaneously survived the surgical procedure and the following 28 days. Skin thinning over the implant occurred in 25% of the animals in weeks 5-6. Phase II-Following single incision subcutaneous implantation 72% of the animals were terminated within the 28-day postsurgery due to skin rupture over the implant body, with only 22% of the animals viable after 28 days. Following double incision subcutaneous implantation 86% of animals were viable after 28 days and thus the recommended method for implantation.

DISCUSSION

The improvements to the surgical approach have improved survival rates and increased the potential for robust, long term use of telemetered guinea pig colonies for screening for QT prolonging potential and additional cardiovascular assessment in vivo.