Background: Chronic Obstructive Pulmonary Disease (COPD) is the first cause of Heart Failure with preserved Ejection Fraction (HFpEF). Relationship between emphysema and diastolic dysfunction is poorly understood. Hyperinflation and inflammation are the main hypothesis.
We developed a study model involving eosinophilic depletion with the use of an anti-Interleukin-5 (mepolizumab, anti-IL5).

Objective: to assess the impact of eosinophilic depletion on cardiovascular properties in an emphysematous rat model.

Methods: We used a Wistar rat model with emphysema generated by intra-tracheal instillation of elastase (ELA) (10UI) at week 1,2,3 and 4. Lipopolysaccharide (LPS) (2,5mg/kg) was instilled with the last ELA instillation, to mimic an exacerbation. Anti-IL-5 (2 mg) was injected intra-peritoneally every 3 weeks from the beginning. We compared 6 different groups (control; ELA; ELA-LPS; anti-IL5 alone; ELA-anti-IL5; ELA-LPS-anti-IL5). We performed cardiac stress test on metabolic treadmill and echocardiography to characterize systolic and diastolic function. Blood samples were collected to measure IL5 concentration and eosinophil number. Heart and lungs were harvest to assess pulmonary compliance and embedded in paraffin for histology analyses.

Results: We observed a significant improvement of diastolic function in the groups with anti-IL5. We observed an exercise intolerance at the acute phase post-instillation with the persistence 5 weeks later, less important in the treated groups. Emphysema was associated with increased lung compliance and decreased elastance.

Conclusion: In our model, eosinophilic depletion seems beneficial on the diastolic cardiac dysfunction induced by emphysema.