New Orleans -- For thousands of years, the overwhelming majority of Tibetans have remained at the roof of the world, characterized by average altitudes in excess of 12,000 feet. Living in this hypoxic environment, has necessitated that humans and animals adapt, developing mechanisms to compensate for low oxygen levels and facilitate metabolism and other physiological functions.

For the individual permanently residing at sea level, hypoxia can be caused by external factors, such as a sudden arrival in Tibet, or by "internal impairments," within the body where cells receive insufficient oxygen. Regardless of the cause of the hypoxia, a wide range of disorders may occur.

How can Tibetans function normally at altitudes that would eventually capacity the rest of us? It is known that organisms may adjust who body functions, modify some metabolic pathways, and change the sensitivity of the "injury threshold" to increase a tolerance to hypoxia. But what is unclear is whether that adjustment is acclimatization, capable of occurring during an extended period in a high altitude environment, or adaptation, requiring several generations in high altitudes for tolerance to occur.

Tibet and its native population have previously offered researchers a "natural laboratory" for the study of hypoxia, the environment, and physiological responses to both. Past findings include verification that Tibetans are adaptive in nature, and have significantly less polycythemia (excessive red blood cells) and hypoventilation, normally found in "lowlanders'" mountain sickness. To compare genetic differences and resistant reactions between Tibetans and lowlanders could offer clues for preventing hypoxia, whether it is caused by a change in environment or as a result of the body's processes.

The authors of the study, "Intrinsic Characteristic Tolerance to Acute Hypoxia in Tibetans after Migrating to Low Altitude," are Zhao-Nian Zhou, J.G. Zheng, X. F. Wu, and L.Q. He, all from the Shanghai Institute of Physiology, Chinese Academy of Sciences, Shanghai, People's Republic of China. They will deliver the results of their investigation during the American Physiological Society’s (APS) annual meeting, part of the "Experimental Biology 2002: conference. More than l4,000 will attend the conference, which is being held April 20-24, 2002 at the Ernest N. Morial Convention Center, New Orleans, LA.

The study subjects consisted of the following cohorts:

• Ten lowlander males born in a sea level environment had not visited a high altitude environment for four years. Any previous acclimatization would have dissipated after three years.

• Thirty-three Tibetan males raised in an environment higher than 10,000 feet had migrated to Shanghai and not returned in the immediate four year time period.

Age, body-weight, and height were similar; hypoxia was introduced into the subjects by placing them into a hypobaric chamber for two hours, at a simulated height of more than 11,000 feet.

Hypoxic tolerance was evaluated during acute hypoxia with cardiac-pump reserve capacity, exercise performance, oxygen transport ability, and activation of the autonomic nervous system.

During acute hypoxia, the lowlander group displayed: (1) decreased in physical work capacity; (2) a decrease in arterial oxygen partial pressure and saturation; (3) a decrease in cardiac pump-reserve capacity; and (4) a potential risk for mountain sickness.

The Tibetan group results were opposite, with the induced hypoxia causing no deterioration in any of the physiological processes measured.

The findings demonstrate that the Tibetans' superior physical performance and adaptive ability to acute hypoxia are confirmed after migrating to low altitude. Differences in gene expression in relevant pathways between the two groups need to be explored continuously.

Identification of these pathways could lead to novel approaches for treatment of hypoxic injury among patients undergoing cardiac surgery and prevention of mountain sickness among the world's growing number of mountain climbers.

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