Translational Research: Multi-Scale Models of the Pulmonary Circulation in Health and Disease - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 258

In general, the pulmonary blood vessels have thinner walls and are less mus-
cular than systemic blood vessels of similar size, yet localized active regulation of
smooth muscle tone is an important mechanism for controlling gas exchange
function in the lung [ 35 ]. In addition to active mechanisms, passive changes to the
pulmonary vascular system can have a far greater effect than in the systemic
circulation: pulmonary vascular resistance (PVR) and the distribution of blood can
be significantly altered by changes in cardiac output, posture, and the rate or depth
of breathing. Abnormalities in the pulmonary circulation can lead to impaired gas
exchange efficiency or significant increases in RV afterload and impaired cardiac
function. Therefore, understanding normal and abnormal function in the pul-
monary circulation is essential in consideration of lung disease.
The lung provides an interface between air and blood, through which oxygen
(O 2 ) is carried to the body and carbon dioxide (CO 2 ) released to the atmosphere.
Air pressure varies through the breathing cycle meaning that pulmonary blood
vessels (particularly the capillaries that cover the alveoli) are exposed to changes
in external pressure unlike that of any other blood vessels in the body. The caliber
of pulmonary vessels varies with breathing: with inflation the intra-alveolar vessels
compress in height and the extra-alveolar vessels increase in diameter; with
deflation the intra-alveolar vessels increase in height and the extra-alveolar vessels
decrease in diameter [ 36 ]. Changes in vessel caliber with lung inflation and the
pulsatility of blood flow in the lung results in a complex, yet coordinated, temporal
variability in blood flow that is dependent on both the rate of breathing and heart
rate. This makes the morphometry of the lung difficult to study in vitro conditions
and necessitates the inclusion of air-blood interactions in modeling the pulmonary
circulation.
Structurally the pulmonary circulation differs from the systemic circulation,
most notably at the micro-scale. Whilst the systemic capillaries have a 3-D 'tree-
like' structure, the pulmonary capillaries form a dense 2-D mesh [ 1 ]. The systemic
circulation has distinct arterioles with a single smooth muscle layer that connect
arteries to capillaries. There is no distinct anatomical definition of pulmonary
arterioles in terms of muscularization. However, small blood vessels—from which
capillary beds arise—that branch in and between the alveolar airways are some-
times termed arterioles [ 31 , 37 , 38 ]. As the lung carries almost the entire cardiac
output via a low pressure, low resistance system, large pulmonary arteries have a
relatively thin medial wall compared with systemic arteries, which makes them
more distensible, and so more readily adaptable to pressure variations than the
systemic arteries.
As the lung does not have distinct, muscular pre-capillary vessels it is thought
that control of pulmonary blood flow, and its matching to local ventilation, is
achieved by a combination of structural and gravitational influences [ 12 - 16 ]. This
control is 'fine-tuned' via active mechanisms [ 39 ], which include a further unique
attribute of the pulmonary circulation: its response to hypoxia. Whilst systemic
blood vessels dilate in response to hypoxia, the pulmonary blood vessels contract
when alveolar (air-side) oxygen is low [ 40 , 41 ]. Like other blood vessels, pul-
monary vessels also dilate when nitric oxide (NO) levels increase, with NO