PATHOGENESIS OF HIGH-ALTITUDE PULMONARY-EDEMA - DIRECT EVIDENCE OF STRESS FAILURE OF PULMONARY CAPILLARIES

The pathogenesis of high-altitude pulmonary oedema (HAPE) is disputed, Recent reports show a strong correlation between the occurrence of HA PE and pulmonary artery pressure, and it is known that the oedema is o f the high-permeability type, We have, therefore, proposed that HAPE i s caused by ultrastructural damage to pulmonary capillaries as a resul t of stress failure of their walls, However, no satisfactory electron microscopy studies are available in patients with HAPE, and animal mod els are difficult to find. Madison strain Sprague-Dawley rats show a b risk pulmonary pressure response to acute hypoxia and are susceptible to HAPE, We exposed 13 Madison rats to a pressure of 294 torr for up t o 12.5 h, or 4 rats to 236 torr for up to 8 h, Pulmonary arterial or r ight 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 lu ngs were fixed for electron microscopy with intravascular glutaraldehy de. Frothy bloodstained fluid was seen in the trachea of three animals . Ultrastructural examination showed evidence of stress failure of pul monary 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 wai l interstitium, proteinaceous fluid and RBCs in the alveolar spaces, a nd fluid-filled protrusions of the endothelium into the capillary lume n. These appearances are consistent with the ultrastructural changes w e have previously described in rabbit lung when the capillaries are ex posed to high transmural pressures, and we conclude that the pathogene sis of HAPE is stress failure of pulmonary capillaries.