Functional Assays used for Cardiac Safety
Cardiac safety is one of the main causes of trial delay and drug abandonment. Assessment of drug-induced proarrhythmic risk and cardiac dysfunction at multiple levels is critical to modern cardiac safety screening. Aurora offers an integrative approach to various functional assays for compound screening.
Action Potential of Purkinje fibers
Purkinje fibers are thought to be an important site for the initiation of arrhythmias. They are particularly sensitive to hERG inhibition and therefore to drug-induced prolongation of action potential duration (APD) and early after depolarization (EAD). Compared to ventricular muscles, Purkinje fibers may be a better model for studying QT prolongation-related torsade de Pointes (TdP). Aurora offers physiologically relevant rabbit whole-ventricle Purkinje fibers preparation for assessment of drug effect on action potential duration.
Inhibition of hERG by defetilide increases action potential duration & induces EADs
Cardiomyocyte Contractility is controlled by the excitation-contraction coupling machinery involving Ca2+ influx and efflux within myocytes. Impairment to this regulatory machinery can lead to serious cardiac conditions. Aurora uses the IonOptix system (Milton, MA, USA) to record real-time changes in sarcomere length of single isolated cardiomyocytes through video acquisition. Ca2+ cycling is monitored in parallel by recording Ca2+ transients from fura-2 loaded isolated cardiomyocytes. This unique system allows us to investigate the details of cellular mechanisms of drug-induced negative or positive inotropy.
Emerging evidence against using QT prolongation as a surrogate maker of proarrhythmia necessitates the need for adopting more predictable drug testing models. Aurora provides a clinically relevant rabbit Torsades de Pointes (TdP) model to assess compound effects on ECG intervals and their proarrhythmic and anti-arrhythmic potential.
Left Ventricular Pressure-Volume Analysis
Left ventricular pressure-volume analysis in rats provides insights into pharmacological impacts on cardiac systolic and diastolic function in anesthetized animals. Aurora uses the SciSense Admittance PV-Catheter technology to accurately measure left ventricular pressure and volume in real-time.