Genetic susceptibility to high-altitude pulmonary edema

 

Masayuki Hanaoka

First Department of Medicine, Shinshu University School of Medicine

 

Some of the individuals may not acclimatize to the rapidly exposed hypobaric hypoxia in high altitude and fail to adapt to the hypoxic environment, leading to high-altitude illnesses, such as acute mountain sickness, high-altitude pulmonary edema (HAPE). The subjects with a history of HAPE showed significantly higher level of pulmonary arterial pressure with an exercise load at low altitude compared with subjects without a history of HAPE. In addition, the mean pulmonary arterial pressure was around 25 mmHg in subjects without development of HAPE, while over 40 mmHg in subjects with development of HAPE, at altitude of 4,559 m. It is proposed that the bio-synthesis of nitro oxide (NO) in the subjects with a history of HAPE is impaired, inducing an increase in pulmonary artery pressure, and eventually leading to the onset of HAPE. The deficiency of NO generates exaggerated hypoxic vasoconstriction unevenly in pulmonary circulation in subjects with a history of HAPE, resulting in a significantly shift of pulmonary blood flow from high-pressure region to low-pressure region in pre-capillary segment. With the increased inner pressure in local capillaries, the vascular endothelium suffers from a strong “shear stress”. As a result, the alveolus-capillary barrier is crashed, and red blood cells and serum proteins leak in a direction from capillaries to alveolar spaces (stress failure theory). The studies in Japan and India demonstrated that the frequencies of genetic polymorphisms of the endothelial NO synthase gene were significantly higher in the subjects with a history of HAPE than the subjects without a history of HAPE. It is strongly suggested that NO is associated with the development of HAPE underlying a genetic background.

 

Key words: Gene, High-altitude pulmonary edema, Nitro oxide, Pulmonary hypertension, Shear stress