Biomedical Engineering Reference
In-Depth Information
of pulmonary hypertensive disorders, pulmonary hypertension associated
with chronic respiratory diseases (i.e., COPD) and with hypoxia are consid-
ered together (107). This notion arises from demonstrated effects of hypoxia
on pulmonary circulation. Indeed, chronic exposure of animals to hypobaric
pressures or reduced inspired O
2
concentration results in SMC and adven-
titial fibroblast proliferation (108,109). Because pulmonary arteries contract
in front of hypoxic stimulus, it has been considered that SMC proliferation
in pulmonary vessels of COPD patients represents an adaptation to this
chronic stimulus. In fact, genes potentially involved in this vascular remo-
deling process, such as TGF-
b
, platelet-derived growth factor (PDGF)
and intercellular adhesion molecule-1 (ICAM-1) might be activated by
increased shear stress during vasoconstriction (110).
The condition that more specifically represents chronic adaptation to
hypoxia is that of subjects living at high altitude. Morphometric studies con-
ducted by Arias-Stella and Salda ˜a (111) in natives living in Cerro del Pasco
(4330m altitude) showed that the most prominent change in pulmonary
arteries was an increased thickness of the muscular layer. Furthermore,
Heath et al. (112) showed that in highlanders the most characteristic feature
in pulmonary arteries was medial thickening, whereas intimal measurements
did not differ from control subjects. These morphological changes differ
from those shown in COPD patients, where, as discussed above, the most
prominent changes occur in the intima, whereas medial hypertrophy is
rarely seen, even in subjects with advanced disease and profound hypoxemia
(5,12). Indeed, in some occasions, medial thickness of patients with
advanced disease and chronic respiratory failure is lower than in patients
with moderate disease (13) (Fig. 1).
It is of note that in COPD, there is great variability in the individual
responses of the pulmonary circulation to acute changes in inspired oxygen
concentration (4,113,114). Hemodynamic measurements conducted in
COPD patients while breathing an hypoxic mixture have shown different
responses in pulmonary vascular resistance (marked increase, no change,
or even decrease) that were unrelated to the degree of airflow obstruction,
hypoxemia, or pulmonary artery pressure while breathing room air (113).
The ultimate goal of hypoxic pulmonary vasoconstriction (HPV) is to main-
tain an adequate matching between ventilation and perfusion. Using mea-
surements of ventilation-perfusion distributions at different inspired O
2
fractions, the authors also showed great variability in the magnitude of
HPV that again was unrelated to the gas exchange status at baseline (4).
Furthermore, there is some evidence that the degree of vasoconstriction
induced by hypoxic stimulus is modulated by the extent of remodeling in
pulmonary arteries (4) and by the endothelial function (115). Overall, these
findings denote that persistent vasoconstriction in response to chronic
hypoxic stimulus does not fully explain pulmonary vascular changes in
COPD.
