Translational Research: Multi-Scale Models of the Pulmonary Circulation in Health and Disease - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 271

influenced by tissue deformation (an effective stretching of large vessels in the
direction of gravity) and posture (prone and supine postures have shorter path-
lengths to dependent lung tissue than upright and a smaller zone 4), is primarily
responsible for the size of zone 4. This supported experimental studies that also
suggested that the mechanism of perfusion reduction in zone 4 was via extra-
alveolar vessel resistance [ 82 ]. The integration of structural and gravitational
features to this multi-scale model of the pulmonary circulation provided important
new physiological insight into the mechanisms behind the normal distribution of
pulmonary perfusion that was not possible by experiment, or by previous sim-
plified computational models. It has also opened the door for integrated studies of
pulmonary function, in combination with similarly structured models of ventila-
tion [ 55 ], as well as allowing for a subject specific approach to studying lung
disease. These translational aspects of computational modeling in the pulmonary
circulation are discussed in detail in Sect. 5 .
5 Translational Outcomes
The ultimate goal of modeling any biological system is to provide physiological
insight and translational outcomes. That is, to enable physiologists, biologists and
physicians to improve knowledge and treatment of pathologies relating to the
system. As the main function of the lung is the exchange of gases between alveolar
air and capillary blood, any disruption to normal function in the pulmonary cir-
culation is likely to translate to disruption to gas exchange function and hence to
the ability of the body to provide oxygenated blood to tissue. A major advantage of
multi-scale, anatomically based models is their ability to relate whole lung func-
tion to localized function. The state-of-the-art in this modeling approach for
simulating regional gas exchange and pulmonary pathologies are introduced in this
section.
5.1 Gas and Solute Exchange and Metabolism
There are many models in the literature that aim to describe gas exchange between
alveolar air and capillary blood in a single 'unit' (this may be a whole lung, a
single alveolus or a group of alveoli). These models have been reviewed in detail,
and related to one another based on a hierarchy of modeling assumptions, by
Ben-Tal [ 84 ]. In general, the relationship between the partial pressure of oxygen in
alveolar air (p AO2 ) and pulmonary capillary blood (p cO2 ) can be expressed as an
ordinary differential equation (ODE)