title: Pathogenesis of high-altitude pulmonary oedema: direct evidence of stress failure of pulmonary capillaries.
abstract: The pathogenesis of high-altitude pulmonary oedema (HAPE) is disputed. Recent reports show a strong correlation between the occurrence of HAPE and pulmonary artery pressure, and it is known that the oedema is of the high-permeability type. We have, therefore, proposed that HAPE is caused by ultrastructural damage to pulmonary capillaries as a result of stress failure of their walls. However, no satisfactory electron microscopy studies are available in patients with HAPE, and animal models are difficult to find. Madison strain Sprague-Dawley rats show a brisk pulmonary pressure response to acute hypoxia and are susceptible to HAPE. We exposed 13 Madison rats to a pressure of 294 torr for up to 12.5 h, or 4 rats to 236 torr for up to 8 h. Pulmonary arterial or right ventricular systolic pressures measured with a catheter increased from 30.5 +/- 0.5 (SEM) in controls (n = 4) to 48 +/- 2 torr (n = 11). The lungs were fixed for electron microscopy with intravascular glutaraldehyde. Frothy bloodstained fluid was seen in the trachea of three animals. Ultrastructural examination showed evidence of stress failure of pulmonary capillaries, including disruption of the capillary endothelial layer, or all layers of the wall, swelling of the alveolar epithelial layer, red blood cells (RBCs) and oedematous fluid in the alveolar wall interstitium, proteinaceous fluid and RBCs in the alveolar spaces, and fluid-filled protrusions of the endothelium into the capillary lumen.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: UCSD Dept of Medicine, La Jolla 92093-0623, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: West
authors.forename: G L
authors.initials: GL
authors.lastname: Colice
authors.forename: Y J
authors.initials: YJ
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Namba
authors.forename: S S
authors.initials: SS
authors.lastname: Kurdak
authors.forename: Z
authors.initials: Z
authors.lastname: Fu
authors.forename: L C
authors.initials: LC
authors.lastname: Ou
authors.forename: O
authors.initials: O
authors.lastname: Mathieu-Costello
mesh_terms: D000532:Altitude Sickness / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002196:Capillaries / Q000503:physiopathology / Q000648:ultrastructure; D002199:Capillary Permeability / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000648:ultrastructure; D008854:Microscopy, Electron; D011654:Pulmonary Edema / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology*