Patterned cardiomyocytes on microelectrode arrays as a functional, high information content drug screening platform

Area of Science:

• Cardiovascular Research
• Drug Development
• Biomedical Engineering

Background:

• Cardiac side effects are a primary reason for drug candidate failure and market withdrawal.
• There is a need for high-throughput screening tools to assess drug-induced cardiotoxicity.
• Existing methods for cardiac electrophysiology lack sufficient information content for comprehensive safety profiling.

Purpose of the Study:

• To develop and validate an enhanced multielectrode array system for cardiac safety screening.
• To improve the measurement of key electrophysiological parameters like conduction velocity and refractory period.
• To create a functional re-entry model for assessing drug effects on cardiac arrhythmias.

Main Methods:

• Utilized commercial multielectrode arrays combined with surface patterning of cardiac myocyte monolayers.
• Enabled measurement of conduction velocity and action potential refractory periods.
• Developed a functional re-entry model for studying cardiac rhythm disturbances.

Main Results:

• 1-Heptanol (gap junction blocker) significantly reduced conduction velocity.
• Sparfloxacin (fluoroquinolone antibiotic) induced rapid, irregular, and unsynchronized activity, indicative of fibrillation.
• The patterned monolayer approach improved temporal resolution and enabled synchronized stimulation for refractory period measurements.

Conclusions:

• Patterned cardiac myocyte monolayers on multielectrode arrays offer enhanced information content for cardiac safety screening.
• This method addresses limitations of traditional multielectrode recordings.
• The platform shows potential for development into a robust cardiac side effect screening tool, especially with human cardiomyocytes.