MyoLoop : Design, development and validation of a standalone bioreactor for pathophysiological electromechanical in vitro cardiac studies

© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society..

Mechanical load is one of the main determinants of cardiac structure and function. Mechanical load is studied in vitro using cardiac preparations together with loading protocols (e.g., auxotonic, isometric). However, such studies are often limited by reductionist models and poorly simulated mechanical load profiles. This hinders the physiological relevance of findings. Living myocardial slices have been used to study load in vitro. Living myocardial slices (LMS) are 300-μm-thick intact organotypic preparations obtained from explanted animal or human hearts. They have preserved cellular populations and the functional, structural, metabolic and molecular profile of the tissue from which they are prepared. Using a three-element Windkessel (3EWK) model we previously showed that LMSs can be cultured while performing cardiac work loops with different preload and afterload. Under such conditions, LMSs remodel as a function of the mechanical load applied to them (physiological load, pressure or volume overload). These studies were conducted in commercially available length actuators that had to be extensively modified for culture experiments. In this paper, we demonstrate the design, development and validation of a novel device, MyoLoop. MyoLoop is a bioreactor that can pace, thermoregulate, acquire and process data, and chronically load LMSs and other cardiac tissues in vitro. In MyoLoop, load is parametrised using a 3EWK model, which can be used to recreate physiological and pathological work loops and the remodelling response to these. We believe MyoLoop is the next frontier in basic cardiovascular research enabling reductionist but physiologically relevant in vitro mechanical studies.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:109

Enthalten in:

Experimental physiology - 109(2024), 3 vom: 22. März, Seite 405-415

Sprache:

Englisch

Beteiligte Personen:

Pitoulis, Fotios G [VerfasserIn]
Smith, Jacob J [VerfasserIn]
Pamias-Lopez, Blanca [VerfasserIn]
de Tombe, Pieter P [VerfasserIn]
Hayman, Danika [VerfasserIn]
Terracciano, Cesare M [VerfasserIn]

Links:

Volltext

Themen:

Cardiac cycle
Electromechanical stimulation
In vitro culture
Journal Article
Living myocardial slices
Mechanical load
MyoLoop

Anmerkungen:

Date Completed 04.03.2024

Date Revised 10.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1113/EP091247

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM363400567