Hoffmann, Peter (2017) An Evaluation of the Drug-induced Changes in Cardiac Inotropy (LVdP/dt40 and QA Interval) and Lusitropy (LVdP/dtmin and Tau) in Dogs: Results from a HESI-sponsored consortium. An Evaluation of the Drug-induced Changes in Cardiac Inotropy (LVdP/dt40 and QA Interval) and Lusitropy (LVdP/dtmin and Tau) in Dogs: Results from a HESI-sponsored consortium, Journa (85). pp. 1-21.

Abstract

The data generated by this ILSI/HESI-sponsored consortium have demonstrated that the conscious, chronically instrumented Beagle dog provides a reliable, consistent preclinical model capable of detecting drug-induced effects on the inotropic state of the heart. Although LVdP/dtmax has been shown recently to provide a robust index of changes in the contractile state of the dog heart (Guth et al., 2105), we have demonstrated that the LVdP/dt40 provided essentially identical results thereby also qualifying it as another index that can be used to assess drug effects on cardiac contractility. In contrast, the QA interval did not react sensitively to the drugs tested. This would not preclude its use in screening approaches designed to detect large, drug-induced effects, approaches perhaps more appropriate in small animal models. Alternatively, since the QA-interval does appear to detect large effects, it could be considered for use in early cardiovascular safety frontloading studies or toxicological studies in which only arterial blood pressure and ECG signals are available, again with the caveat that one may only detect large effects on the inotropic state. Although the indices of the lusitropic state of the heart did not respond in a sensitive manner in this study, the drugs tested may not have been ideally selected to demonstrate lusitropic effects in the conscious dog.

Item Type:	Article
Date Deposited:	08 Feb 2017 00:45
Last Modified:	08 Feb 2017 00:45
URI:	https://oak.novartis.com/id/eprint/30126