Acute effects of cardiac contractility modulation stimulation in conventional 2D and 3D human induced pluripotent stem cell-derived cardiomyocyte models

• DOI: 10.3389/fphys.2022.1023563
• Publication Date: 2022-11-10T09:45:43Z
• Authors: Tromondae K. Feaster; Nicole Feric; Isabella Pallotta; Akshay Narkar; Maura Casciola; Michael P. Graziano; Roozbeh Aschar-Sobbi; Ksenia Blinova
• Keywords: Contractility

Cardiac contractility modulation (CCM) is a medical device therapy whereby non-excitatory electrical stimulations are delivered to the myocardium during absolute refractory period enhance cardiac function. We previously evaluated effects of standard CCM pulse parameters in isolated rabbit ventricular cardiomyocytes and 2D human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) monolayers, on flexible substrate. In present study, we sought extend these results 3D microphysiological systems develop robust model evaluate various clinical vitro. HiPSC-CMs were studied conventional monolayer format, stiff substrate (i.e., glass), as engineered tissues (ECTs). contractile properties by video pixel) force-based analysis. pulses assessed at varying 'doses' using commercial generator. A response was observed for ECTs. Under comparable conditions, hiPSC-CMs, substrate, displayed no response. ECTs enhanced including increased contraction amplitude force), accelerated relaxation slopes under acute stimulation. Moreover, parameter-dependent manner adjustment delay, duration, amplitude, number relative baseline. The subsided when stimulation stopped gradually returned These data represent first study hiPSC-CM models provide nonclinical tool assess signals prior vivo animal studies. this work provides foundation additional devices