Monday  |  Conference Center A  |  09:40 AM–10:00 AM

#13249, Strain as an Indicator of Disease Severity and Mechanical Function in a Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Model

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a heart disease which can lead to sudden death. In this research we combine stem cells derived from a CPVT patient (RyR2-H2464D mutation) and a healthy familial control with a platform developed for use with cardiomyocytes (CMs). The stem cell derived CMs are cultured in vitro on a microcontact printed extracellular matrix (ECM) patterned substrate with adjustable stiffness. The platform, which is amenable to structural, mechanical, and electrical characterization, is used with Fast Iterative Digital Image Correlation (FIDIC) to provide evaluation of strain across collections of cells acting in coordination throughout contraction events. The amplitude of contractile strain is utilized as a quantitative indicator of CM functionality and disease severity. We find statistically significant differences in maximum contractile strains between the patient and control cell lines. The Young’s modulus of the platform substrate was investigated at 10, 30 and 50 kPa, and the maximum contractile strain was found to be consistently higher in the patient samples compared to the control samples for the stiffnesses investigated. Additionally, the patient line had a statistically significantly slower intrinsic contraction rate than the control, which agrees with prior reports in literature using CPVT patient-specific stem cell derived CMs. Our work shows that this difference in intrinsic rate was not correlated with maximum contractile strain. Differences in mechanical strain have not been previously reported, and hypercontractility is not a known characteristic of CPVT. However, functional changes can occur as the disease progresses, so this behavior may represent an early disease phenotype. These results add to the limited studies of mechanical function of CPVT CMs reported in literature and the results demonstrate the utility of this approach in quantifying mechanical function for cardiac disease.

Alana Stempien   University of Wisconsin-Madison
W. de Lange   University of Wisconsin-Madison
J. Hernandez   University of Wisconsin-Madison
Mitchell Josvai   University of Wisconsin-Madison
Jacob Notbohm   University of Wisconsin-Madison
J. Ralphe   University of Wisconsin-Madison
Wendy Crone   University of Wisconsin-Madison