Preservation of contractile characteristics of human myocardium in multi-day cell culture
Abstract
Functional studies of different human cell types have been successfully conducted under in vitro conditions. Despite many efforts, it has not been possible to develop a human myocardial preparation in which contractile function can be studied over several days. We hypothesize that by mimicking the in vivo situation in an in vitro environment we can preserve viability and function of human myocardial preparations over several days. From explanted hearts of patients undergoing cardiac transplantation, multicellular preparations were dissected and mounted in a sterile muscle chamber. Muscles were stimulated at 0.5 or 1 Hz at 1.75 mmol/l Ca(2+), a pH of 7.4 and at 37 degrees C, and kept contracting isometrically for 2-6 days. This study shows for the first time that contractile function of human myocardial tissue can be preserved over several days; active force development had not significantly changed after 48 h (10.6+/-1.2 at t=0 v 11.4+/-2.8 mN/mm(2)at t=48, n=10), nor had diastolic force (1.0+/-0.1 v 0.9+/-0.1 mN/mm(2)). After at least 48 h, the contractile response to stimulation with 1 micromol/l isoproterenol was clearly present: developed force increased to 631+/-146% of control values, while half-relaxation time declined to 57+/-6% (n=7). In addition, both pharmacological responses and regulatory physiological behavior, such as post-rest potentiation and force-frequency relationships, are preserved. This technique allows the study of the regulation of contractile function of human myocardium in vitro and may be used to link changes in protein expression to consequent changes in myocardial contraction.
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Post-rest potentiation behavior of isolated cardiac muscles is species-dependent: rabbits exhibit post-rest decay, while humans and rats show post-rest potentiation.
“Following periods of rest after steady pacing, rabbits exhibit a post-rest decay where the first twitch tension is decreased while humans and rats show post-rest potentiation where the first twitch tension is increased as the rest periods are prolonged (Janssen, Lehnart, Prestle, & Hasenfuss, 1999; Maier, Bers, et al., 2000).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Janssen, et al., 1999
In vitro contraction assessment in human cardiac tissue is a valuable tool for studying drugs or physiological processes.
“Still, despite these difficulties, in vitro assessment of contraction in human cardiac tissue can be an important tool to study drugs or physiological processes (Hermann, et al., 2002; Janssen, et al., 1999; Janssen, et al., 2000; Pieske, et al., 1995; Rossman, et al., 2004).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Janssen, et al., 1999
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- Authors
- Janssen, P. M. L., Lehnart, S. E., Prestle, J., & Hasenfuss, G.
- Affiliations
- University of Göttingen (DE)
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 1999-08
- Volume
- 31
- Issue
- 8
- Pages
- 1419-1427
- ISSN
- 0022-2828 (ISSN-L)
- OpenAlex
- W2089377531
- Cited by
- 59
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2016: 2 · 2014: 3 · 2013: 2 · 2012: 5
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- human myocardium, cardiac contractility, isometric contraction, isoproterenol response, post-rest potentiation, force-frequency relationship, heart transplantation, in vitro tissue culture
- MeSH terms
- Electric Stimulation, Heart, Humans, Myocardial Contraction, Myocardium, Tissue Preservation, Culture Techniques
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