Endothelin-1 and interleukin-8 in high altitude pulmonary oedema

Abstract

E En nd do ot th he el li in n--1 1 a an nd d i in nt te er rl le eu uk ki in n--8 8 i in n h hi ig gh h a al lt ti it tu ud deABSTRACT: We present a case of high altitude pulmonary oedema (HAPE) with pulmonary hypertension and polymorphoneuclear leucocyte (PMN) accumulation in bronchoalveolar lavage fluid (BALF), which occurred in a 21 year old man. Plasma endothelin-1 (ET-1) and interleukin-8 (IL-8) concentration in BALF were elevated on admission, and returned to normal level at recovery, when the pulmonary artery pressure and the PMN counts in BALF were normal. In addition, E-selectin and intercellular adhesion molecule-1 (ICAM-1) in BALF were also slightly increased on admission.These findings suggest that endothelin-1 is a vasoconstrictor which contributes to the pulmonary hypertension in high altitude pulmonary oedema, and that some of the inflammatory mediators play an important role in chemotaxis and accumulation of polymorphonuclear leucocytes in the development of high altitude pulmonary oedema. Eur Respir J., 1996Respir J., , 9, 1947Respir J., -1949. High altitude pulmonary oedema (HAPE) is a severe type of acute mountain sickness. It is a serious, sometimes fatal illness related to rapid exposure to altitude. Although the pathophysiological mechanism of HAPE remains unclear, it has long been suggested that pulmonary vasoconstriction and increased pulmonary vascular permeability are important contributory factors [1,2]. Recent studies have suggested that endothelin is related to pulmonary vasoconstriction [3][4][5], and that the increased pulmonary vascular permeability is probably caused by inflammatory mediators [6][7][8][9][10]. However, no studies have been conducted on the role of endothelin and cytokines in patients with HAPE. We report a case of HAPE, documenting the possible role of endothelin-1 (ET-1), and polymorphoneuclear leucocyte (PMN) chemotactic mediators, such as interleukin-8 (IL-8). Case reportA Japanese male university student, aged 21 yrs, who was healthy before climbing, arrived at the foot of the Japan Alps at 1,000 m above sea level. The next morning, he started climbing to a snowy valley about 2,000 m above sea level and still felt well. On the third day, whilst climbing to Mt Yari (3,180 m), he developed general fatigue, followed by headache, cough, sputum, poor appetite and fever (38˚C). After staying all day to rest at 3,000 m, his condition progressively deteriorated. On the fifth day, he was lethargic, comatose, cyanotic, and had a cough with foamy sputum. He was rescued, transported by helicopter, and admitted to our Shinshu University Hospital (660 m).On admission, he had cyanosis and was unconscious. His temperature was 38˚C, pulse rate 140 beats·min -1 , respiration rate 26 breaths·min -1 , and his blood pressure 140/90 mmHg. Coarse crackles were audible over both sides of the lung. He showed decerebrate rigidity. An examination of the ocular fundi showed papilloedema and multiple flame-shaped and blot haemorrhages in both fundi. A chest roentgenogram revealed patc...

High‐altitude Pulmonary Edema: Review

“…Combined actions of EDN-1 and nitric oxide might play an important role in regulating vascular tone and blood pressure. EDN-1 is considered a contributor to the pathogenesis of HAPE 71,72) . The findings of Sartori et al (1999) suggest that in HAPE-susceptible mountaineers, an augmented release of the potent pulmonary vasoconstrictor peptide endothelin-1 and/or its reduced pulmonary clearance could represent one of the mechanisms contributing to exaggerated pulmonary hypertension at high altitudes 71) .…”

Endothelin B Receptor Deficiency Predisposes to Pulmonary Edema Formation via Increased Lung Vascular Endothelial Cell Growth Factor Expression

“…ET, a potent pulmonary vasoconstrictor, also may contribute to the pathogenesis of HAPE, given that plasma ET levels are elevated in humans with HAPE. 8,9 ET acts through two receptor subtypes, the ET-A and ET-B receptors. Activation of vascular ET-A receptors leads to vasoconstriction, whereas activation of vascular ET-B receptors leads to either nitric oxide-mediated vasodilation (when endothelial ET-B receptors are activated) or to vasoconstriction (when smooth muscle ET-B receptors are activated).…”

Physical activity at moderate and high altitudes. Cardiovascular and respiratory morbidit

“…Increase in the plasmatic ET-1 has been observed in cases of HAPE (high-altitude pulmonary edema), including in the bronchoalveolar lavage, and it is part of one of the hypotheses about the pathogenesis of HAPE 33 .…”

“…Teleradiography shows diffuse alveolar images unevenly distributed 19,38,45 . The alveolar fluid is rich in proteins and inflammatory mediators 33,45,52,53 .…”

“…Exposure to a continuous increase in altitude progressively increases plasmatic endothelin 1 (ET-1) 32,33 , which is a peptide synthesized by endothelial cells, with potent vasoconstrictive and mitogenic action upon the vascular smooth muscles.…”