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Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

Publisher

MDPI
DOI: 10.3390/ijerph18041692

Keywords

high altitude; hypoxic pulmonary vasoconstriction; high altitude pulmonary edema; pulmonary hypertension; chronic mountain sickness

Funding

  1. German Research Foundation (DFG) [268555672-CRC1213]
  2. Universities of Giessen and Marburg Lung Center (UGMLC)
  3. Excellence Cluster Cardio-Pulmonary System
  4. Cardiovascular Medical Research and Education Fund (CMREF)
  5. Ministry of education and science of the Kyrgyz Republic [0005823]

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Alveolar hypoxia in high altitude environments leads to pulmonary hypertension and potentially life-threatening disorders such as high altitude pulmonary edema. While vasodilators show promise in reducing pulmonary artery pressure in residents at high altitudes, no approved drugs currently exist for treating chronic high altitude pulmonary hypertension.
Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring at high altitudes in non-acclimatized healthy individuals. Despite a strong physiologic rationale for using vasodilators for prevention and treatment of HAPE, no systematic studies of their efficacy have been conducted to date. Calcium-channel blockers are currently recommended for drug prophylaxis in high-risk individuals with a clear history of recurrent HAPE based on the extensive clinical experience with nifedipine in HAPE prevention in susceptible individuals. Chronic exposure to hypoxia induces pulmonary vascular remodeling and development of pulmonary hypertension, which places an increased pressure load on the right ventricle leading to right heart failure. Further, pulmonary hypertension along with excessive erythrocytosis may complicate chronic mountain sickness, another high altitude maladaptation disorder. Importantly, other causes than hypoxia may potentially underlie and/or contribute to pulmonary hypertension at high altitude, such as chronic heart and lung diseases, thrombotic or embolic diseases. Extensive clinical experience with drugs in patients with pulmonary arterial hypertension suggests their potential for treatment of high altitude pulmonary hypertension. Small studies have demonstrated their efficacy in reducing pulmonary artery pressure in high altitude residents. However, no drugs have been approved to date for the therapy of chronic high altitude pulmonary hypertension. This work provides a literature review on the role of pulmonary hypertension in the pathogenesis of acute and chronic high altitude maladaptation disorders and summarizes current knowledge regarding potential treatment options.

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