Cardiac adverse events are the leading cause of discontinuation of clinical trials and account for almost 25% of all drug withdrawals from the market in the US. Cardiotoxicity encompasses a number of conditions that cause damage to the heart muscle and include cardiac dysfunction, heart failure, myocardial ischemia, valvular abnormalities, pericardial disease, hypertension, and arrhythmias. Today, cardiac toxicity has become a major concern in the development of new cancer treatments given that a number of targeted therapies and next-generation cell- and antibody-based immunotherapies have been shown to affect the cardiovascular system.
ERBC is a world leader in the field of cardiac toxicology. In addition to classical methods to measure cardiac functions, ERBC uses telemetry to perform measurements in conscious, freely moving animals over long periods of time spanning from several hours up to several days. Being one of the first European laboratories to adopt this technique, ERBC has accumulated extensive experience in telemetric studies over a 20 year-period.
Acute study in catheterized conscious animals
- Species: rats
- Applications: detection of cardiotoxic effects of a test substance in the absence of any interaction with an anaesthetic agent
Haemodynamic study in anaesthetized rats
- Administration routes: intravenous, intracerebroventricular or intracisternal (sub-cerebellar cistern)
- Measurements: systolic, diastolic and mean blood pressure; heart rate; regional arterial flow rates
Haemodynamic study in other anaesthetized animals
- Species: Dogs, cynomolgus monkeys, marmosets, minipigs, cats, rabbits
- Measurements: systolic, diastolic and mean blood pressure; heart rate; electrocardiogram; PR, QRS, QT intervals; regional arterial flow rates; cardiac output; left ventricular pressure; pulmonary artery pressure; central venous pressure; arterial and venous blood gases; global myocardial O2 consumption
PV loop method
- Species: rats, dogs, cynomolgus monkeys
- Measurements: cardiac output; stroke volume; ejection fraction; dLVP/dt (max) and dLVP/dt (min); heart rate; end-systolic left ventricular volume; end-diastolic left ventricular volume; end-systolic left ventricular pressure; end-diastolic left ventricular pressure; left ventricular compliance; left ventricular contractility
Isolated and perfused heart (according to Langendorff)
- Species: guinea pig, rat
- Measurements: cardiac contractility; heart rate; coronary flow
Torsade de Pointes in conscious or anaesthetised rabbits
Telemetry in conscious animals
- Species: dog, guinea pig, rat, marmoset, cynomolgus monkey, minipig, cat
- Measurements: heart rate; cardiac conduction times (PR, QRS, QT and QTc intervals); short term variability of ventricular repolarisation, arrhythmia occurrence; haemodynamics (blood pressure, systolic ejection volume, cardiac output, peripheral arterial resistance, strength of left ventricular contraction, regional blood flows); autonomic nervous system
