The lung is extremely sensitive to interstitial fluid balance, yet the role of pulmonary lymphatics in lung fluid homeostasis and its interaction with cardiovascular pressures is poorly understood. In health, there is a fine balance between fluid extravasated from the pulmonary capillaries into the interstitium and the return of fluid to the circulation via the lymphatic vessels. This balance is maintained by an extremely interdependent system governed by pressures in the fluids (air and blood) and tissue (interstitium), lung motion during breathing, and the permeability of the tissues. Chronic elevation in left atrial pressure (LAP) due to left heart disease increases the capillary blood pressure. The consequent fluid accumulation in the delicate lung tissue increases its weight, decreases its compliance, and impairs gas exchange. This interdependent system is difficult, if not impossible, to study experimentally. Computational modelling provides a unique perspective to analyse fluid movement in the cardiopulmonary vasculature in health and disease. We have developed an initial in silico model of pulmonary lymphatic function using an anatomically structured model to represent ventilation and perfusion and underlying biophysical laws governing fluid transfer at the interstitium. This novel model was tested against increased LAP and non-cardiogenic effects (increased permeability). The model returned physiologically reasonable values for all applications, predicting pulmonary oedema when LAP reached 25 mmHg and with increased permeability.

Pulmonary hypertension (PH) has multiple etiologies, and so can be difficult to diagnose, prognose, and treat. Diagnosis is typically made via invasive hemodynamic measurements in the main pulmonary artery, and is based on observed elevation of mean pulmonary artery pressure. This static mean pressure enables diagnosis, but does not easily allow assessment of the severity of PH, nor the etiology of the disease, which may impact treatment. Assessment of the dynamic properties of pressure and flow data obtained from catheterization potentially allows more meaningful assessment of the strain on the right heart, and may help to distinguish between disease phenotypes. However, mechanistic understanding of how the distribution of disease in the lung leading to PH impacts the dynamics of blood flow in the main pulmonary artery and/or the pulmonary capillaries is lacking. We present a computational model of the pulmonary vasculature, parameterized to characteristic features of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) to help understand how the two conditions differ in terms of pulmonary vascular response to disease. Our model incorporates key features known to contribute to pulmonary vascular function in health and disease, including anatomical structure and multiple contributions from gravity. The model suggests that dynamic measurements obtained from catheterization potentially distinguish between distal and proximal vasculopathy typical of PAH and CTEPH. However, the model suggests a non-linear relationship between these data and vascular structural changes typical of PAH and CTEPH which may impede analysis of these metrics to distinguish between cohorts.

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