Hypoxia-Induced Pulmonary Blood Redistribution in Subjects With a History of High-Altitude Pulmonary Edema

Abstract

Background-Pulmonary hypertension has been suggested to play an important role in development of high-altitude pulmonary edema (HAPE), and individual susceptibility has been suggested to be associated with enhanced pulmonary vascular response to hypoxia. We hypothesized that much greater pulmonary vasoconstriction would be induced by acute alveolar hypoxia in HAPE-susceptible (HAPE-s) subjects and that changes in pulmonary blood flow distribution could be demonstrated by radionuclide study. Methods and Results-We performed ventilation-perfusion scintigraphy in 8 HAPE-s subjects and 5 control subjects while each was in the supine position and acquired functional images of pulmonary blood flow and ventilation under separate normoxic and hypoxic (arterial oxygen saturation, 70%) conditions. We also measured acceleration time/right ventricular ejection time (AcT/RVET) with Doppler echocardiography under each condition in both groups. Moreover, we assayed human leukocyte antigen (HLA) alleles serologically in the HAPE-s group. Pulmonary blood flow was significantly shifted from the basal lung region to the apical lung region under hypoxia in HAPE-s subjects, although no significant change in regional ventilation was observed. With Doppler echocardiography, HAPE-s subjects showed increased pulmonary arterial pressure during hypoxia compared with control subjects. The magnitude of cephalad redistribution of lung blood flow was significantly higher in the HLA-DR6 -positive than in HLA-DR6 -negative HAPE-s subjects. Conclusions-These findings suggest that acute hypoxia induces much greater cephalad redistribution of pulmonary blood flow that results from exaggerated vasoconstriction in the basal lung in HAPE-s subjects. Furthermore, pulmonary vascular hyperreactivity to hypoxia may be associated with HLA-DR6.

Interstitial pressure and lung oedema in chronic hypoxia

“…As oedema formation is strictly related to blood perfusion, one may hypothesise that the heterogeneity in blood perfusion may indeed account for lung regional differences in interstitial fluid dynamics. A recent high-resolution study [20] suggests that the main factors affecting the distribution of pulmonary blood flow may reflect the intrinsic individual topology and geometry of the anatomical arterial vessel: in practice, local vascular resistances. In support of this hypothesis is the finding that an increase in heterogeneity in pulmonary blood flow was found in subjects with a history of HAPE exposed to hypoxia, compared with normal subjects [21].…”

An anesthesiologist's guide to hypoxic pulmonary vasoconstriction: implications for managing single-lung anesthesia and atelectasis

“…There is considerable variation in the strength of HPV within the patient population even at sea level. For example, many patients with prior HAPE have unusually strong HPV, which may contribute to their HAPE susceptibility [24]. The genetic basis for variable HPV responsiveness is unknown.…”

“…For example, hypoxia is the normal state in utero and HPV contributes to the high pulmonary vascular resistance (PVR) that diverts blood away from the nonventilated, fetal lung [23]. HPV is commonly experienced on ascent to altitude, and excessive HPV can contribute to high altitude pulmonary edema (HAPE) [24]. …”

Short-term hypoxic exposure at rest and during exercise reduces lung water in healthy humans

“…Additionally, changes in D M track changes in Vc, although it is likely that correcting D M for Vc (D M /Vc) should accurately estimate changes in D M and, therefore, lung water. Finally, increases or decreases in forced vital capacity (FVC) and maximal expiratory flow rates should follow changes in either thoracic blood volume or lung water.Typically, exposure to hypoxia causes an increase in DL CO , which is caused, at least in part, by an increase in Vc (12,13,19,20,22,62,64). The increase in Vc with hypoxia is a result of elevations in pulmonary pressure caused from heterogenous pulmonary vasoconstriction (64, 65).…”