Abstract
Ventilation‐Perfusion (V/Q) matching is a critical determinant of efficient gas exchange in the pulmonary circulation. The regulatory mechanisms that control V/Q matching under normal and pathological scenarios are incompletely understood. In this study we present the derivation and validation of a multi‐scale computer model of hemodynamics and gas exchange accounting for the fractal‐like pattern of pulmonary vascular branching, mechanical coupling of blood‐tissue interactions, gas exchange, hemoglobin biochemistry, and vasoregulatory mechanisms. By simulating the regional distribution of V/Q ratios, this model serves as an in‐silico platform to test and refine hypotheses regarding the contributions of vasoregulatory mechanisms to regional perfusion and V/Q matching in the lung. Figure 1 depicts the various model “blocks” and how they are interconnected. The complete model is formulated as an algebraically constrained system of ordinary and partial differential equations and is parameterized to represent function in an adult Sprague Dawley rat. Block (A) illustrates the whole‐lung vascular network model. The network geometry is generated by a space‐filling algorithm and is validated by comparing anatomical predications (length, radius, and connectivity) to morphometric data (from existing literature). Block (B) shows how the mechanics of each vessel segment is represented as a lumped system. Mechanics are validated by comparing model predictions to macro‐scale pressure‐flow relationships and pulmonary artery pressure waveforms (from existing literature and our own in vivo studies). Block (C) depicts a representative gas exchange unit. Block (D) portrays oxygen‐sensitive vasoregulatory mechanisms that have been implicated in the maintenance of pulmonary vasomotor tone. Model simulations illustrate that perfusion heterogeneity is governed by the geometry of the vascular tree, and local interaction between alveolar and vascular pressures. Moreover, conducted vascular responses (hypoxic pulmonary vasoconstriction, and the hypoxia‐mediated/mechanically‐transduced release of ATP from red blood cells) modulate the redistribution of blood flow in response to pathological insults such as a pulmonary embolism. Taken together, our results suggest that more homogenous blood flow distributions increase the bulk oxygen content entering the systemic circulation.Support or Funding InformationNIH/NINDS R01 NS087147NIH/NHLBI R01 HL127151This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call