Semi-mechanistic modelling platform to assess cardiac contractility and haemodynamics in preclinical cardiovascular safety profiling of new molecular entities.

ABSTRACT:

Background and purpose

Cardiovascular safety is one of the most frequent causes of safety-related attrition both preclinically and clinically. Preclinical cardiovascular safety is routinely assessed using dog telemetry monitoring key cardiovascular functions. The present research was to develop a semi-mechanistic modelling platform to simultaneously assess changes in contractility (dPdt_max ), heart rate (HR) and mean arterial pressure (MAP) in preclinical studies.

Experimental approach

Data from dPdt_max , HR, preload (left ventricular end-diastolic pressure [LVEDP]) and MAP were available from dog telemetry studies after dosing with atenolol (n = 27), salbutamol (n = 5), L-N^G -nitroarginine methyl ester (L-NAME; n = 4), milrinone (n = 4), ver

SUBMITTER: Venkatasubramanian R 

PROVIDER: S-EPMC7348097 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature