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Murine Short Axis Ventricular Heart Slices for Electrophysiological Studies

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Prolonged Hypoxia in Rat Living Myocardial Slices Affects Function, Expression, and Structure.

Florian J G Waleczek^1,2, Giuseppe Cipriano¹, Jonas A Haas¹

¹Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany.

International Journal of Molecular Sciences

|January 11, 2025

Summary

Hypoxia significantly impairs heart tissue function, causing reduced force and increased damage in living myocardial slices. This study introduces a new model for investigating cardiac responses to low oxygen conditions.

Keywords:

force generation gene expression hypoxia proteome rat living myocardial slices tissue model

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Area of Science:

Cardiovascular Science
Physiology
Molecular Biology

Background:

Ischemic heart disease is a global health burden.
Myocardial hypoxia from reduced oxygen supply causes heart damage.
The effects of hypoxia on multicellular living myocardial slices (LMSs) are not well understood.

Purpose of the Study:

To investigate the primary functional, structural, and molecular effects of hypoxia in a rat LMS model.
To analyze changes in force generation, gene expression, and proteome under reduced oxygen conditions.
To establish LMSs as a novel model for studying hypoxia-induced cardiac changes.

Main Methods:

Ex vivo culture of rat living myocardial slices (LMSs) for 24 hours.
Exposure to normal and reduced oxygen (O2) levels.
Analysis of force generation, tissue ultrastructure, gene expression (transcriptomics), and protein expression (proteomics).

Main Results:

Hypoxia significantly reduced absolute force and slowed force kinetics in LMSs.
Increased cardiomyocyte apoptosis, myofibrillar, and mitochondrial damage were observed.
Proteomic analysis revealed deregulation of proteins involved in metabolism, hypoxic response, and reactive oxygen species neutralization.

Conclusions:

Hypoxia induces significant primary changes in heart tissue independent of perfusion and immune responses.
The rat LMS model effectively demonstrates hypoxia-induced cardiac dysfunction.
This model offers a valuable platform for drug development and mechanistic studies in cardiovascular research.