In vivo QT and Cardiac Hemodynamic Assessment
Determine the effects of drugs on the ECG, arterial blood pressure and body temperature in radiotelemetry-implanted beagle dogs. The canine in vivo model is considered to be the gold standard for sensitive, continuous recording of the ECG and arterial blood pressure in conscious, freely moving animals.
Standard Testing Paradigm
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Parameters Measured
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Figures 1-2. dl-Sotalol Hydrochloride Prolongs the QT Interval in a Reverse Use-Dependent Manner The vehicle (aqueous 1% MC solution) and dl-sotalol hydrochloride were administered as oral gavage doses. The data represent the mean ± SEM of results obtained from four dogs (N = 4). In the bottom panel, prolongation of the QT interval by dl-sotalol increases at longer RR intervals (reverse use-dependence).
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Figure 3. Pinacidil Increases Heart Rate. The vehicle (aqueous 0.5% MC solution) and pinacidil were administered as oral gavage doses. The data represent the mean ± SEM of results obtained from four dogs (N = 3).
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Figure 4. Pinacidil Decreases Systolic Blood pressure. The vehicle (aqueous 0.5% MC solution) and pinacidil were administered as oral gavage doses. The data represent the mean ± SEM of results obtained from three dogs (N = 3).
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Final reports of the in vivo QT study include drug effects on all study parameters including a summary of the results, description of methods used, statement of quality standard, and any amendments or deviations included as an appendix.
The in vivo QT Service is a component of ChanTest’s Thorough Preclinical Cardiac Risk Assessment Package (TSP), a comprehensive cardiac safety assessment package for full resolution of potential cardiac risk prior to IND submission. The TSP includes the hERG Concentration Response Assay, Cardiac Ion Channel Panel™ Concentration Response Assays, APD measured in stem cell-derived human ventricular myocytes, hERG trafficking and the in vivo QT study. The TSP provides the most complete preclinical cardiac safety package presently available.
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