Vivonics offers an anaesthetised model for general cardiovascular screening or investigatory studies. The anaesthetised rat has been shown to be useful when utilised early in the lead optimisation phase of drug discovery. This high throughput model can be used to assess on- or off-target safety liabilities to help project decision-making before more expensive regulatory studies in larger species are conducted. There is good concordance of drug-induced cardiovascular effects between this model and larger conscious animals and humans. Anaesthesia can blunt baroreceptor reflexes, but this may make the model more sensitive to detecting underlying cardiovascular changes and may also emulate the situation in many patient populations with reduced baroreceptor sensitivity (e.g. the elderly, hypertensive patients). Intravenous administration means small amounts of test substance are required. Plasma concentrations can be obtained without any stress-induced cardiovascular changes and it is usually possible to explore a larger dose range than in conscious animals due to the absence of dose-limiting behavioural effects.
The model allows a greater variety of physiological endpoints to be measured making it more amenable for investigations into mechanisms of acute cardiovascular toxicity. Parameters available include: arterial and venous blood pressures, left and right ventricular pressures, ECG, blood flow in various vascular beds, cardiac output, respiratory parameters, blood gas, chemistry and metabolism and also urine samples.
Vivonics Preclinical Ltd,
Biohub at Alderley Park,
Alderley Edge, Cheshire,
The effects of an intravenous phenylephrine challenge on cardiovascular haemodynamics