Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death worldwide caused by pollution and cigarette smoke. This leads to an airflow limitation and parenchymal destruction (emphysema). The disease is worsened by exacerbations mainly due to pulmonary infections. Cardiac dysfunction is a common feature of the disease suggesting a cross-talk between pulmonary and cardiac function.

We aim to understand the early modifications leading to cardiac dysfunction in an animal model that mimic some alterations found in COPD.

We developed a rat model of elastase-induced emphysema with pulmonary septic exacerbation (ELA-LPS). Pulmonary and cardiovascular contractile functions were explored in-vivo and ex-vivo. Excitation-contraction coupling and sarcomere mechanics were studied in isolated cardiomyocytes.

ELA and LPS lead to emphysema with obstruction corresponding to COPD definition. Animals exhibit cardiac hypertrophy and diastolic dysfunction with preserved ejection fraction assessed by echocardiography. ECG reveals tachycardia and rhythmic variability abolition along with sympathic over-stimulation. In perfused heart, RVs present increased sensitivity of developed pressure due to pre-load, associated with RV hypertrophy. At cellular level, LV isolated cardiomyocytes present increased activity, highlighted by increased calcium transients with increased diastolic Ca²⁺. Furthermore, increased passive tension in sarcomeres without modification of calcium sensitivity is observed. Utilization of ß-blocker bisoprolol reverses most of alterations: rhythm, diastolic dysfunction, calcium coupling.

ELA-LPS animal model expresses features of COPD associated to HFpEF. Pathogenesis seems to be associated with ß-adrenergic over-stimulation as echo, ECG and CEC analysis suggest, confirmed by the ß-blocker treatment. Analysis of molecular effectors could highlight specific targets to treat COPD patients.