Pulmonary Blood Flow Heterogeneity during Hypoxia and High-Altitude Pulmonary Edema

Abstract

Uneven hypoxic pulmonary vasoconstriction has been proposed to expose parts of the pulmonary capillary bed to high pressure and vascular injury in high-altitude pulmonary edema (HAPE). We hypothesized that subjects with a history of HAPE would demonstrate increased heterogeneity of pulmonary blood flow during hypoxia. A functional magnetic resonance imaging technique (arterial spin labeling) was used to quantify spatial pulmonary blood flow heterogeneity in three subject groups: (1) HAPE-susceptible (n = 5), individuals with a history of physician-documented HAPE; (2) HAPE-resistant (n = 6), individuals with repeated high-altitude exposure without illness; and (3) unselected (n = 6), individuals with a minimal history of altitude exposure. Data were collected in normoxia and after 5, 10, 20, and 30 minutes of normobaric hypoxia FI(O(2)) = 0.125. Relative dispersion (SD/mean) of the signal intensity was used as an index of perfusion heterogeneity. Oxygen saturation was not different between groups during hypoxia. Relative dispersion was not different between groups (HAPE-susceptible 0.94 +/- 0.05, HAPE-resistant 0.94 +/- 0.05, unselected 0.87 +/- 0.06; means +/- SEM) during normoxia, but it was increased by hypoxia in HAPE-susceptible (to 1.10 +/- 0.05 after 30 minutes, p < 0.0001) but not in HAPE-resistant (0.91 +/- 0.05) or unselected subjects (0.87 +/- 0.05). HAPE-susceptible individuals have increased pulmonary blood flow heterogeneity in acute hypoxia, consistent with uneven hypoxic pulmonary vasoconstriction.

Acute high-altitude sickness

“…If arterial vasoconstriction in hypoxia is inhomogeneous, HAPE could be the consequence of higher flows in those areas with lesser vasoconstriction, leading to increased microvascular pressure. MRI of lung blood flow demonstrates that HPV is uneven at rest in susceptible individuals [77,78], but not in those with proven HAPE resistance. This unevenness in regional HPV may help to explain the characteristic patchy and nodular appearance of oedema in HAPE.…”

Advances in magnetic resonance imaging of lung physiology

“…ASL measurements of regional pulmonary perfusion have been used to demonstrate increases in pulmonary flow heterogeneity in subjects who have previously suffered high-altitude pulmonary edema (HAPE), a potential fatal disease associated with rapid travel to high altitude (41). It has been hypothesized that hypoxic pulmonary vasoconstriction may be nonuniform in HAPE, an idea supported by the work of Hlastala et al in mammalian lungs (40).…”

“…The relative dispersion is a useful measure for globally quantifying the extent of spatial heterogeneity, but the obvious disadvantage is that the measure eliminates any anatomic information. Nevertheless, being able to quantitatively characterize one data set as having a different heterogeneity than another has been shown to be a useful tool (39,41). Spatial correlation provides another means of quantitatively comparing the nature of the spatial information contained in an image.…”

Functional Imaging: CT and MRI

“…Several studies have now demonstrated the feasibility of this technique for assessment of normal and pathological processes. (152)(153)(154)(155) This application is now very close to general introduction into clinical practice.…”