Chronic Obstructive Pulmonary Disease (COPD), the third leading cause of death worldwide, has two main components: distal airways obstruction and emphysema (destruction of lung parenchyma). This chronic condition is complicated by disease exacerbations, mainly due to infections. COPD patients often present numerous comorbidities, particularly cardiac, which are linked to poor clinical prognosis. Our team previously developed an animal model of exacerbated emphysema: “ELA-LPS” rats, which exhibit heart failure with preserved ejection fraction (HFpEF) 5 weeks after exacerbation, as seen in clinics.

We aimed to determine whether the cardiovascular effects observed in ELA-LPS rats are correlated with the extent of pulmonary emphysema and investigate the influence of aging.

Emphysema was induced in male Wistar rats by weekly elastase (ELA) instillations for 4 weeks. The final instillation included bacterial lipopolysaccharide (LPS) to induce exacerbation. In vivo experiments and euthanasia were performed 5 weeks after. Firstly, we tested different doses of elastase (4U, 6U, 10U) in 6-week-old rats to assess whether cardiovascular consequences depend on emphysema severity. Secondly, a dose of 10U elastase was used in 18-month-old rats to study aging effects. Pulmonary emphysema was evaluated by histology and lung compliance was measured ex vivo, while in vivo plethysmography assessed respiratory function. Cardiovascular properties were evaluated in vivo by tail-cuff blood pressure measurement, echocardiography, and maximal cardiorespiratory exercise test (VO2max).

In 6-week-old rats, lung histology confirmed elastase dose-dependent emphysema. This led to increased compliance and respiratory dysfunction. ELA-LPS rats exhibited dose-dependent arterial hypertension and HFpEF (preserved LVEF, increased E/E′ ratio), with diastolic dysfunction correlated to emphysema severity (R²=0.53, P=0.0003). These abnormalities resulted in reduced exercise tolerance during VO2max tests. Furthermore, aging worsened impairments, as older rats showed more severe dysfunctions. Notably, old ELA-LPS rats developed heart failure with reduced ejection fraction (HFrEF).

Our procedure induced a dose-dependent emphysema with vascular, cardiac (dose-dependent diastolic dysfunction), and general consequences in adult rats. Aging significantly affected the phenotype, with older rats developing HFrEF.