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Cardio.Long Service

Ncardia’s Cardio.Long Service provides a cardiac safety profile of your test compounds over a longer time frame. The basis of this service consists of a combination of electrophysiology and impedance monitoring of fully functional and validated hiPSC-derived cardiomyocytes after compound treatment, which is followed by a thorough analysis by our electrophysiology and impedance experts.

Drug-induced arrhythmia and structural cytotoxicity underlie complex mechanisms. Therefore, we provide the Cardio.Long service to study acute to long-term (30 minutes – 48 hours) compound-effects on the electrophysiological behavior and the viability of cardiomyocytes. For instance, the drug pentamidine delays the terminal repolarization in the human heart. This is not caused by acutely blocking cardiac inward rectifier currents, but by chronically reducing plasma membrane expression of the cardiac hERG potassium channel (Dennis, Wan and Ficker, 2007). Hence, the effect only becomes evident after longer incubation times. This example emphasizes the need for long-term cardiotoxic analysis in order to decrease the risk of missing cardiotoxic effects by acute measurements only.

Workflow

Service specifications

Cell type

Human iPSC-derived cardiomyocytes

Service type

Electrophysiology & impedance functional analysis

Format

2 x 48 wells

Time points

Cardiotoxic safety temporal study (0, 0.5, 1, 2, 8, 24 and 48 hours after compound addition)

Compound concentrations*

0.1, 1, 10 µM in medium + 0.1% DMSO (in triplicates)

Positive controls

L-type Ca2+ channel blocker: Nifedipine

hERG channel blocker: Dofetilide

Vehicle control

0.1% DMSO

Parameters

Electrophysiology: beat rate, beat rate coefficient of variation (CoV), field potential duration (FPD), depolarization peak amplitude, proarrhythmic events

Contractility: impedance amplitude and peak width

Timelines

5 Weeks (for up to 8 compounds)

Deliverable

A study protocol will be sent to initiate the study. Results are sent as draft and final study report.

*Suggested concentrations, to be agreed with client