The conventional isoproterenol-induced heart failure model does not consistently mimic the diaphragmatic dysfunction observed in patients
Cabrera-Aguilera, Ignacio (Hospital del Mar (Barcelona, Catalunya))
Falcones, Bryan (Universitat de Barcelona)
Calvo-Fernández, Alicia (Universitat Autònoma de Barcelona. Departament de Medicina)
Benito, Begoña (Universitat Autònoma de Barcelona. Departament de Medicina)
Barreiro, Esther (Hospital del Mar (Barcelona, Catalunya))
Gea Guiral, Joaquim (Hospital del Mar (Barcelona, Catalunya))
Farré, Ramon (Universitat de Barcelona)
Almendros, Isaac (Universitat de Barcelona)
Farré, Núria (Universitat Autònoma de Barcelona. Departament de Medicina)

Fecha:	2020
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	PloS one, Vol. 15 (july 2020) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0236923
PMID: 32730329

17 p, 1.6 MB

El registro aparece en las colecciones:
Artículos > Artículos de investigación
Artículos > Artículos publicados