Diastolic Cardiomyopathy Secondary to Experimentally Induced Exacerbated Emphysema
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.
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