A New Animal Model for Investigation of Mechanical Unloading in Hypertrophic and Failing Hearts: Combination of Transverse Aortic Constriction and Heterotopic Heart Transplantation
Open accessAbstract
OBJECTIVES: Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC) and heterotopic heart transplantation (hHTx) in rats. METHODS: To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations. RESULTS: 50 TAC procedures were performed with a survival of 92% (46/50). When compared to healthy rats left ventricular surface decreased to 5.8±1.0 mm² (vs. 9.6± 2.4 mm²) (p = 0.001) after three weeks with a fractional shortening (FS) of 23.7± 4.3% vs. 28.2± 1.5% (p = 0.01). Six weeks later, systolic function decreased to 17.1± 3.2% vs. 28.2± 1.5% (p = 0.0001) and left ventricular inner surface increased to 19.9±1.1 mm² (p = 0.0001). Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46). All transplanted organs survived two weeks of mechanical unloading. DISCUSSION: Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure.
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The ICR suckling mice model has allowed investigation of some aspects of ZIKV-caused symptoms, including viral-related mortality, clinical score increase, and viral propagation rise.
“Similarly, the ICR suckling mice model allowed the investigation of some aspect of ZIKV-caused symptom including viral-relative mortality, clinical score increasing, and viral propagation rising [22, 32].”
From ICR suckling mouse model of Zika virus infection for disease modeling and drug validation (2018) · cites this paper as [22]
The Background describes a rat model for mechanical unloading in hypertrophic and failing hearts, not a ZIKV infection model. Searches for ICR suckling mice, ZIKV, mortality, clinical scores, and viral propagation found no passage in our copy addressing the attributed claim. (LLM, conf=0.78)
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- Authors
- Schaefer, A., Schneeberger, Y., Stenzig, J., Biermann, D., Jelinek, M., Reichenspurner, H., Eschenhagen, T., Ehmke, H., & Schwoerer, A. P.
- Affiliations
- Universität Hamburg (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Schaefer, Andreas
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-02-03
- Volume
- 11
- Issue
- 2
- Pages
- e0148259
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4739720
- OpenAlex
- W2266156709
- Cited by
- 11
- References
- 23
- Citations by year
- 2024: 2 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 4
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Mechanical Circulatory Support Devices
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- mechanical unloading, heart failure, cardiac hypertrophy, transverse aortic constriction, heterotopic heart transplantation, animal models, left ventricular remodeling, pressure overload, left ventricular dilatation, graft survival, systolic function
- MeSH terms
- Animals, Aorta, Disease Models, Animal, Heart, Cardiomegaly, Heart Failure, Heart-Assist Devices, Male, Rats, Inbred Lew, Heart Transplantation, Transplantation, Heterotopic, Ventricular Remodeling, Rats
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