The conventional isoproterenol-induced heart failure model does not consistently mimic the diaphragmatic dysfunction observed in patients

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• dc.contributor.author Cabrera-Aguilera, Ignacio
• dc.contributor.author Falcones, Bryan
• dc.contributor.author Calvo-Fernández, Alicia
• dc.contributor.author Benito Villabriga, Begoña
• dc.contributor.author Barreiro Portela, Esther
• dc.contributor.author Gea Guiral, Joaquim
• dc.contributor.author Farré, Ramon
• dc.contributor.author Almendros, Isaac
• dc.contributor.author Farré López, Núria
• dc.date.accessioned 2020-09-30T10:11:38Z
• dc.date.available 2020-09-30T10:11:38Z
• dc.date.issued 2020
• dc.description.abstract Heart failure (HF) impairs diaphragm function. Animal models realistically mimicking HF should feature both the cardiac alterations and the diaphragmatic dysfunction characterizing this disease. The isoproterenol-induced HF model is widely used, but whether it presents diaphragmatic dysfunction is unknown. However, indirect data from research in other fields suggest that isoproterenol could increase diaphragm function. The aim of this study was to test the hypothesis that the widespread rodent model of isoproterenol-induced HF results in increased diaphragmatic contractility. Forty C57BL/6J male mice were randomized into 2 groups: HF and healthy controls. After 30 days of isoproterenol infusion to establish HF, in vivo diaphragmatic excursion and ex vivo isolated diaphragm contractibility were measured. As compared with healthy controls, mice with isoproterenol-induced HF showed the expected changes in structural and functional echocardiographic parameters and lung edema. isoproterenol-induced HF increased in vivo diaphragm excursion (by ≈30%, p<0.01) and increased by ≈50% both ex vivo peak specific force (p<0.05) and tetanic force (p<0.05) at almost all 10-100 Hz frequencies (p<0.05), with reduced fatigue resistance (p<0.01) when compared with healthy controls. Expression of myosin genes encoding the main muscle fiber types revealed that Myh4 was higher in isoproterenol-induced HF than in healthy controls (p<0.05), suggesting greater distribution of type IIb fibers. These results show that the conventional isoproterenol-induced HF model increases diaphragm contraction, a finding contrary to what is observed in patients with HF. Therefore, this specific model seems limited for translational an integrative HF research, especially when cardio-respiratory interactions are investigated.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cabrera-Aguilera I, Falcones B, Calvo-Fernández A, Benito B, Barreiro E, Gea J, Farré R, Almendros I, Farré N. The conventional isoproterenol-induced heart failure model does not consistently mimic the diaphragmatic dysfunction observed in patients. PLoS One. 2020; 15(7):e0236923. DOI: 10.1371/journal.pone.0236923
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0236923
• dc.identifier.issn 1932-6203
• dc.identifier.uri http://hdl.handle.net/10230/45358
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.ispartof PLoS One. 2020; 15(7):e0236923
• dc.rights © 2020 Cabrera-Aguilera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Heart failure
• dc.subject.keyword Thoracic diaphragm
• dc.subject.keyword Isoproterenol
• dc.subject.keyword Muscle contraction
• dc.subject.keyword Mouse models
• dc.subject.keyword Edema
• dc.subject.keyword Muscle analysis
• dc.subject.keyword Skeletal muscles
• dc.title The conventional isoproterenol-induced heart failure model does not consistently mimic the diaphragmatic dysfunction observed in patients
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion