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 suggested hypothesis. We developed a study model involving eosinophilic depletion with two strategies implying the use of an anti-Interleukin-5 (mepolizumab or rat-specific anti-IL-5 antibody).

To assess the impact of eosinophilic depletion on cardiovascular properties in an emphysematous rat model.

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 (1.7μg) or Mepolizumab (4mg) were injected intra-peritoneally every 3weeks from the beginning. We compared 6 different groups (control; ELA-LPS; ELA-LPS anti-IL5; ELA-LPS-MEPO; control-anti-IL5; control-MEPO). We performed cardiac stress test on metabolic treadmill, blood pressure assessments and echocardiography to characterize systolic and diastolic function. Blood samples have been collected to measure eosinophilic inflammation (IL5 concentration and eosinophil number). After sacrifice heart and lungs were removed to assess pulmonary compliance and were embedded in paraffin for histology analyses.

We observed an improvement of diastolic function (E/E′ decreased at week 9) in the treated groups, when compared to ELA-LPS group. We observed a reduction of the distance travelled during the metabolic test in the ELA-LPS group when compared to other groups. Emphysema was associated with increased lung compliance, and an increase in systolic and diastolic blood pressure, whereas results appeared to improve in treated groups.

In this model, the modification of inflammatory characteristics by eosinophilic depletion seems beneficial on the diastolic cardiac dysfunction induced by emphysema.