Consequences of exacerbation in old rats with emphysema

Abstract

Introduction

Chronic Obstructive Pulmonary Disease (COPD), is marked by chronic airflow limitation due to small airway obstruction and emphysema, which involves abnormal enlargement of lung air spaces and inflammation-induced tissue destruction. COPD often coexists with cardiovascular diseases, likely due to chronic inflammation. As an age-related disease, COPD's effects are worsened with aging, intensifying both lung and systemic impacts. However, the connection between age-related emphysema and cardiac issues remains unclear, indicating a need for more research on how aging affects COPD's impact on cardiovascular health.

Methods

Old male Wistar rats (18 months old, n = 9 control, 5 ELA-LPS) received weekly intra-tracheal instillations of elastase (ELA) over 4 weeks at a dose of 10 U. I to induce emphysema. In the fourth week, alongside elastase, bacterial lipopolysaccharide (LPS) derived from E. coli O55 B: 5 was delivered to mimic a bacterial exacerbation. We evaluated pulmonary, cardiac and muscular functions using various in-vivo and ex-vivo methods, including cardiorespiratory tests on a treadmill, whole-body plethysmography and echocardiography. The results in aged animals were compared with those from young animals (6–7 weeks-old).

Results

Preliminary results revealed significant alteration in cardiac systolic function, along by morphological changes in the left ventricular posterior wall during systole and diastole, compared to the young emphysema model, where a correlation between emphysema and diastolic dysfunction was noted. Unexpectedly, there was a trend of improvement in respiratory parameters, including Peak Inspiratory Flow, Peak Expiratory Flow, and tidal volume. The cardiorespiratory performance test showed a trend towards reduced O₂ consumption and decreased exercise capacity, consistent with aging patterns. Then, the assessment of lung elastic properties (ex vivo pressure-volume curve) indicated a greater loss of pulmonary elasticity compared to the young emphysematous model. Additionally, ex vivo endurance and force tests on the soleus muscle showed a tendency toward reduced muscle endurance and strength, aligning with the findings from the treadmill test.

Conclusion

This multidisciplinary approach seeks to deepen our understanding of the age-related aspects of COPD-emphysema and its broader impact on human health. Initial results are promising, showing that aged rats exhibit a more severe phenotype than younger ones. Once confirmed, the underlying causes of these age-related dysfunctions compared to younger animals need to be determined to provide valuable insights into associated cardiac disorders.