The impact of environmental and biological factors on the resting heart rate of dogs as assessed using 20 years of data from safety pharmacology studies

Abstract

IntroductionA safety pharmacology study detects and evaluates potential side effects of a new drug on physiological function at therapeutic levels and above and, in most cases, prior to the initiation of clinical trials. The aim of this study was to investigate the effects of environmental and biological factors on resting heart rate (HR), a representative cardiac parameter in cardiovascular safety pharmacology. MethodsOver twenty years, 143 dogs (Beagles, Labradors and mongrels) received implanted telemetry transmitters to measure aortic pressure (AP), left ventricular pressure (LVP), Electrocardiogram (ECG) and body temperature. Throughout the 7-h period of data collection, data were continuously recorded without drug treatment and included the range of HRs resulting from spontaneous physiological changes. Statistics and visualizations were calculated using R and Spotfire. ResultsBeagles had a higher HR than the mongrels, while Labradors had a lower HR than mongrels. Labradors were found to have a sex-based difference in HR, with females having a higher HR. A higher HR was observed in young animals of all breeds when they were in contact with humans. The cage system affected the HR of Labradors and mongrels more than Beagles. Larger dogs (e.g. Labrador) have a lower HR than smaller dogs (Beagles). Animals that are younger were found to have more HR variability and have a higher HR than older animals. In addition, older animals reacted less to the application period and human interaction than younger animals. The HR response of animals inside a cage system may depend on the cage system in which they were bred. A familiar cage system typically has less impact on HR. DiscussionThis retrospective data base evaluation has demonstrated the impact of environmental and biological factors on cardiovascular parameters in the context of performing safety pharmacology studies. Breed, sex, age and the type of cage system used affected, at least in some cases, the HR and its variability. They should therefore be carefully considered when designing safety pharmacology studies to have the highest possible test sensitivity.