Diastolic Cardiomyopathy Secondary to Experimentally Induced Exacerbated Emphysema - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue American Journal of Respiratory Cell and Molecular Biology Année : 2023

Diastolic Cardiomyopathy Secondary to Experimentally Induced Exacerbated Emphysema

Quentin Wynands
  • Fonction : Auteur

Résumé

Chronic Obstructive Pulmonary Disease (COPD) is a clinical entity of increasing significance.COPD involves abnormalities of the airways and in emphysema, parenchymal pulmonarydestruction. Cardiovascular disease has emerged as a significant comorbidity to COPD. HeartFailure with preserved Ejection Fraction (HFpEF) appears to be particularly associated withCOPD-Emphysema. Traditional treatments have shown limited efficacy in improving COPDassociated HFpEF. This lack of therapeutic efficacy highlights the need to identify potentialmechanisms that link COPD-Emphysema to HFpEF. Therefore, we aimed to study the delayedcardiac physiological impacts in a rat model with acute exacerbated emphysema. Emphysema wasinduced by 4 weekly 4UI elastase intra-tracheal pulmonary instillations and exacerbation by onefinal additional LPS instillation in male Wistar rats. At 5 weeks following the LPS/elastaseexposure, in-vivo and ex-vivo pulmonary and cardiac measurements were performed. Experimentalexacerbated emphysema resulted in decreased pulmonary function and exercise intolerance.Histological analysis revealed parenchymal pulmonary destruction without signs of inflammationor cardiac fibrosis. In-vivo cardiac functional analysis revealed diastolic dysfunction andtachycardia. Ex-vivo analysis revealed a cellular cardiomyopathy with decreased myofilament Ca2+sensitivity, cross-bridge cycling kinetics and increased adrenergic PKA-dependentphosphorylation of troponin-I. Experimental exacerbated emphysema was associated with exerciseintolerance that appeared to be secondary increased β-adrenergic tone and subsequent cardiacmyofilament dysfunction. A β1-receptor antagonist treatment (bisoprolol) started 24h post ELALPSinstillation prevented in-vivo and ex-vivo diastolic dysfunction. These results suggest that novel treatment strategies targeted to the cardiac myofilament may be beneficial to combatexacerbated emphysema associated HFpEF.
Fichier principal
Vignette du fichier
Red-2022-0382OC.R2_Proof_hi.pdf (3.96 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-04094438 , version 1 (18-10-2023)

Identifiants

Citer

Pierre-Edouard Grillet, Elodie Desplanche, Quentin Wynands, Fares Gouzi, Patrice Bideaux, et al.. Diastolic Cardiomyopathy Secondary to Experimentally Induced Exacerbated Emphysema. American Journal of Respiratory Cell and Molecular Biology, 2023, 69 (2), ⟨10.1165/rcmb.2022-0382OC⟩. ⟨hal-04094438⟩
42 Consultations
40 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More