An in silico approach to understanding the interaction between cardiovascular and pulmonary lymphatic dysfunction

The lung is extremely sensitive to interstitial fluid balance, yet the role of pulmonary lymphatics in lung fluid homeostasis and its inter-action with cardiovascular pressures is poorly understood. In health, there is a fine balance between fluid extravasated from the pul-monary 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 dur-ing 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 modeling provides a unique perspective to analyze fluid movement in the cardiopulmonary vasculature in health and disease. We have devel-oped 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 noncardiogenic effects (increased permeability). The model returned physiologically reasonable values for all applications, predicting pulmonary edema when LAP reached 25 mmHg and with increased permeability. NEW & NOTEWORTHY This model presents a novel approach to understanding the interaction between cardiac dysfunction and pulmonary lymphatic function, using anatomically structured models and biophysical equations to estimate regional variation in fluid transport from blood to interstitial and lymphatic flux. This fluid transport model brings together advanced models of ven-tilation, perfusion, and lung mechanics to produce a detailed model of fluid transport in health and various altered pathological conditions.