Mechanism For Life-Threatening High-Altitude Sickness Uncovered

High altitude pulmonary edema (HAPE) is a life-threatening complication of rapidly going to high altitude. The condition causes fluid retention in the lungs and it is characterized by extreme listlessness, inability to walk or sleep, coughing up blood or sputum, and a "strange" sensation in the chest. It can develop when a person ascends rapidly to heights greater than 2,500 meters (8,250 feet). Not everyone is susceptible to HAPE.

Previous hypotheses were that air pressure at higher altitudes caused swelling in the capillaries (tiny blood vessels within the lungs), or that the capillaries become leaky as a result of inflammation.

"We could not find any signs of inflammation," says Marco Maggiorini, M.D., lead investigator of the study, and physician in the intensive care unit at the University of Zurich, in Switzerland. "We did find elevated pressure in the capillaries, which leads to water in the lungs, or pulmonary edema."

Maggiorini notes that pulmonary edema can be treated with vasodilators. His study confirms that vasodilators can lower pulmonary capillary pressures, which is now known to cause the disorder. "The condition is strictly related to a lack of oxygen in the air when climbers or hikers reach certain altitudes. As soon as you give oxygen or a vasodilator, the pressure goes down."

Anyone who spends time at very high altitudes who is susceptible to HAPE may want to talk with their doctor about taking vasodilators with them when they travel, says Maggiorini. "Vasodilators can be used to prevent HAPE as well as treat it," he says. "Mountaineers may want to use vasodilators before they travel to areas like the Alps, the Rocky Mountains, the Himalayas, the Andes, or other high altitudes."

Researchers compared 16 climbers who had previously experienced HAPE, to 14 climbers who had never developed the condition. Using an invasive technique known as a right heart catheterization, researchers examined blood pressure in the pulmonary artery (leading from the heart to the lungs), and measured permeability of the pulmonary capillaries. Permeability has to do with the ability of molecules to move from the capillaries into the alveoli (air sacs of the lungs). These measurements were taken first at low altitude (490 meters or 1,617 feet), then within 24 hours after ascent to a higher altitude (4,559 meters or 15,045 feet).

At the lower altitude, HAPE-susceptible subjects experienced the same degree of hypoxia, or reduced oxygen in their blood, but had higher constriction in their pulmonary blood vessels compared to the control group. At the higher altitude, HAPE-susceptible individuals had higher average pulmonary artery pressure (37 mm Hg) and capillary pressure (19 mm Hg), compared to controls, whose average pulmonary artery and capillary pressure was 26 mm Hg and 13 mm Hg, respectively.

Maggiorini reports that nine of the susceptible individuals actually developed HAPE. All nine had pulmonary capillary pressures greater than 19 mm Hg, whereas the seven susceptible climbers who did not develop HAPE had pulmonary capillary pressures less than 19 mm Hg.

HAPE-susceptible individuals developed modestly leaky capillaries, but capillary permeability remained within the normal range, and was no different than that found in the control group, says Maggiorini.

"There are no tests for high altitude pulmonary edema," says Maggiorini. "Climbers would do well to familiarize themselves with the symptoms of the disorder, so they can prevent a life-threatening emergency."

Study co-authors are Christian Mélot, M.D.; Sebastien Pierre, M.D.; Fredi Pfeiffer, Ph.D.; Ilone Greve, M.S.; Claudio Sartori, M.D.; Mattia Lepori, M.D.; Markus Hauser, M.D.; Urs Scherrer, M.D.; and Robert Naeije, M.D.