Stretch-Induced Remodeling of Human Living Cardiomyocyte Slices AHA Conference Repository

American Heart Association

Final ID: Mon090

Stretch-Induced Remodeling of Human Living Cardiomyocyte Slices

Abstract Body: Background: Physiological preload is a critical determinant of cardiac function through the Frank–Starling mechanism, yet most in vitro models fail to recapitulate controlled loading conditions. Dilated Cardiomyopathy is characterized by chronic elevation of preload, ventricular dilation, and impaired contractility. Living myocardial slices (LMS) preserve native myocardial architecture and provide a platform to investigate load-dependent cardiac remodeling.
Methods: Non-failing human myocardium was sectioned into living LMS (7mm×7mm×300 µm), which were mounted on 3D-printed anchors and maintained for 5 days in a custom culture platform permitting independent control of preload and afterload. Slices were continuously paced at 0.25 Hz and assigned to one of three loading conditions for the duration of culture: Low Preload (slack length), Physiological Preload (15% stretch beyond slack length), or High Preload (25% stretch beyond slack length). Following culture, contractile performance was evaluated by generating force–length work loops using the IonOptix system. Tissue was subsequently processed for histological and molecular analyses to assess cardiomyocyte morphology and cell area.
Results: LMS cultured under Low and Physiological Preload conditions demonstrated improved tissue viability and faster contractile kinetics compared to High Preload. Physiological Preload produced optimal passive force and preserved cardiomyocyte morphology, characterized by elongated, rod-shaped cells with maintained alignment. In contrast, High Preload resulted in reduced passive force generation and disrupted cellular architecture, including loss of alignment and abnormal morphology.
Conclusions: Controlled application of physiological preload preserves contractile function and tissue architecture in human LMS, whereas elevated preload induces functional and structural changes consistent with early features of Dilated Cardiomyopathy. Ongoing studies will quantify sarcomere length and assess Titin expression to further define the role of passive stiffness in preload-dependent dysfunction. This platform provides a physiologically relevant model to study stretch-induced cardiac remodeling and disease mechanisms.

Webb, Megan ( University of Pennsylvania , Wellesley , Massachusetts , United States )
Pizarro, Sebastian ( University of Pennsylvania , Wellesley , Massachusetts , United States )
Rosa, Francisco ( University of Pennsylvania , Philadelphia , Pennsylvania , United States )
Bedi, Kenneth ( UNIVERSITY OF PENNSYLVANIA , Philadelphia , Pennsylvania , United States )
Bouhrira, Nesrine ( University of Pennsylvania , Philadelphia , Pennsylvania , United States )
Margulies, Kenneth ( UNIV PENNSYLVANIA SCH OF MEDICINE , Philadelphia , Pennsylvania , United States )

Author Disclosures:

Meeting Info:

Basic Cardiovascular Sciences 2026

2026

Boston, Massachusetts

Session Info:

Poster Session 1

Monday, 07/13/2026 , 04:30PM - 07:00PM

Poster Session and Reception

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