Cardiac Safety Assessment Services

Cardiotoxicity in Drug Discovery

Drug-induced cardiotoxicity remains a leading cause of compound attrition and post-market drug withdrawals. The most significant cardiovascular liability is Torsades de Pointes (TdP), a life-threatening ventricular arrhythmia associated with delayed cardiac repolarization and QT interval prolongation on the electrocardiogram.

Historically, cardiac safety screening focused primarily on the hERG potassium channel (Kv11.1), which conducts the rapid delayed rectifier current (IKr) critical for cardiomyocyte repolarization. However, hERG-centric screening can overestimate proarrhythmic risk, as compounds with multi-channel effects may have offsetting pharmacology. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative addresses this limitation by integrating ion channel panels, in silico modeling, and confirmatory human cardiomyocyte studies to improve TdP risk prediction.

Regulatory Framework for Cardiac Safety
ICH S7B guidelines require nonclinical evaluation of QT/QTc prolongation and proarrhythmic potential prior to first-in-human studies. The CiPA paradigm, endorsed by FDA and under consideration by global regulators, recommends a mechanistic approach incorporating multiple cardiac ion channels (hERG, Nav1.5, Cav1.2) and functional endpoints to generate more predictive and clinically translatable cardiac safety data.

Ion Channel Screening

Ion channels regulate cardiac electrical activity by controlling sodium, potassium, and calcium ion flow across the cell membrane. Drug-induced ion channel modulation can disrupt the cardiac action potential and cause arrhythmias. Screening against key cardiac ion channels identifies proarrhythmic liability early.

Available Cardiac Ion Channel Targets

Action Potential Assays

Tissue-based action potential recording captures the net effect of multi-channel pharmacology on cardiac repolarization, providing physiologically integrated endpoints that single-channel assays cannot.

Purkinje Fiber Assay
Rabbit Purkinje fibers are specialized conduction tissue with long action potential durations, making them highly sensitive to repolarization abnormalities. Compound profiling detects effects on action potential duration, upstroke velocity, and resting membrane potential—parameters directly relevant to clinical QT prolongation.

Langendorff Isolated Heart

Ex vivo whole-heart preparation captures integrated cardiac function, electrophysiology, and contractility in an intact organ system—without confounding systemic influences.

ECG and Hemodynamic Endpoints
Retrograde aortic perfusion maintains cardiac function for several hours, enabling simultaneous ECG recording (PR, QRS, QT/QTc) and hemodynamic measurement (LVDP, contractility, heart rate). Detects proarrhythmic signals from multi-channel effects, metabolite activity, and indirect mechanisms not captured by cell-based assays.