Drug Controls High-altitude Illness

The results appear in the first issue for February 2007 of the American Journal of Respiratory and Critical Care Medicine.

Marc J. Poulin, Ph.D., D.Phil., of the Departments of Physiology, Biophysics and Clinical Neuroscience at the University of Calgary in Canada and seven associates showed that acetazolamide had complex effects on ventilation, pulmonary vascular resistance and cerebral blood flow in optimizing brain oxygenation during simulated high-altitude tests on nine subjects. The researchers concluded that the drug could be a valuable means of preventing or treating high-altitude pulmonary edema.

"Acute mountain sickness is one of three major high-altitude-related diseases seen in people who rapidly ascend to altitudes higher than 3,000 meters or 9,843 feet," said Dr. Poulin. "The other two diseases are high-altitude pulmonary edema and high-altitude cerebral edema. Worldwide, an increasing number of sea-level residents--altogether several million a year--visit areas higher than 2,500 meters. Many of them develop symptoms of acute mountain sickness. Among these symptoms are insomnia, headache, lightheadedness, fatigue, breathlessness, lack of appetite and nausea. Acute mountain sickness can precede the more serious problem of high-altitude pulmonary edema."

The authors found that among those susceptible to high-altitude pulmonary edema, acetazolamide decreases lung edema, facilitates the diffusion of oxygen and improves the ventilation/perfusion ratio in the lung.

They also noted that those with the lowest mountain sickness scores after being exposed to a simulated altitude of slightly over 16,000 feet showed the lowest rate of fluid retention.

By directly acting on smooth muscle cells, acetazolamide appears to cause dilation (enlargement) of vessels involved in cerebral blood flow.

"Acetazolamide has been shown to prevent high-altitude pulmonary edema in rats and the agent could prove to be an efficient therapeutic means in the prevention of the disease," said Dr. Poulin. "It could be an alternative to calcium channel blockers, phosphodiesterase inhibitors or inhaled nitric oxide."

Study participants took either 250 milligrams of acetazolamide or a placebo every eight hours for three days. On the fourth test day, the researchers measured the subjects' responses to ventilation, pulmonary vascular resistance and cerebral blood flow during simulated high-altitude tests.

Each treatment period was separated by a 10-day washout to overcome any potential crossover effects from acetazolamide.

In the test group were six men and three women who were slightly over age 28. All were non-smokers with no history of cardio-respiratory disease. They were told to abstain from caffeine, alcohol or strenuous exercise throughout the test period.