Exaggerated Endothelin Release in High-Altitude Pulmonary Edema

Sartori, Cláudio; Vollenweider, L; Löffler, Bernd–Michael; Delabays, Alain; Nicod, Pascal; Bärtsch, Peter; Scherrer, Urs

doi:10.1161/01.cir.99.20.2665

Cited by 127 publications

(72 citation statements)

References 31 publications

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“…Nitric oxide (NO) and endothelin-1 are important pulmonary endothelial-derived vasodilator and vasoconstrictor mediators. Endothelin production is greater in HAPE susceptibility [73], while lung NO production is reduced [56,74,75]. Systemic vascular endothelial NO generation is reduced more in hypoxic HAPE-susceptible subjects compared to controls [76].…”

Section: Haemodynamicsmentioning

confidence: 99%

Acute high-altitude sickness

2017

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At any point 1-5 days following ascent to altitudes ⩾2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain sickness, a syndrome of nonspecific symptoms including headache, lassitude, dizziness and nausea; high-altitude cerebral oedema, a potentially fatal illness characterised by ataxia, decreased consciousness and characteristic changes on magnetic resonance imaging; and high-altitude pulmonary oedema, a noncardiogenic form of pulmonary oedema resulting from excessive hypoxic pulmonary vasoconstriction which can be fatal if not recognised and treated promptly. This review provides detailed information about each of these important clinical entities. After reviewing the clinical features, epidemiology and current understanding of the pathophysiology of each disorder, we describe the current pharmacological and nonpharmacological approaches to the prevention and treatment of these diseases.

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Section: Haemodynamicsmentioning

confidence: 99%

Acute high-altitude sickness

2017

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“…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) .…”

Section: Endothelinmentioning

confidence: 99%

High‐altitude Pulmonary Edema: Review

Bhagi

Srivastava

Singh

2014

Journal of Occupational Health

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High‐altitude Pulmonary Edema: Review: Shuchi BHAGI, et al. Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), India— Objective At High altitude (HA) (elevation >2,500 m), hypobaric hypoxia may lead to the development of symptoms associated with low oxygen pressure in many sojourners. High‐altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non‐acclimatized healthy individuals. It is a multifactorial disease involving both environmental and genetic risk factors. Since thousands of lowlanders travel to high altitude areas for various reasons every year, we thought it would be interesting to review pathological aspects related to hypobaric hypoxia, particularly HAPE. Method Since the pathogenesis of HAPE is still a subject of study, we systematically identified and categorized a broad range of facets of HAPE such as its incidence, symptoms, physiological effects, pathophysiology including physiological and genetic factors, prevention and treatment. Results This review focuses on HA‐related health problems in general with special reference to HAPE, which is one of the primary causes of deaths at extreme altitudes. Hence, it is extremely important, as it summarizes the literature in this area and provides an overview of this severe HA malady for evaluation of physiological, biochemical and genetic responses during early induction and acclimatization to HA. This article could be of broad scientific interest for researchers working in the field of high altitude medicine.

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“…69 Ethnic differences or different linkage disequilibrium in white and Japanese or Indian populations could account for the discrepant results. It is likely that additional factors such as increased sympathetic activity or other vasoconstrictors such as angiotensin II, 70 endothelin, 71 or arachidonic acid metabolites 72 contribute to increased PAP in HAPE-susceptible subjects. Increased skeletal muscle sympathetic activity 73 and increased plasma and/or urinary levels of norepinephrine 70,74 compared with controls were found during hypoxia at low altitude and before and during 74 HAPE.…”

Section: Pulmonary Hypertensionmentioning

confidence: 99%

Effect of Altitude on the Heart and the Lungs

2007

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T his review focuses on the effects of altitude exposure from 1 to several days or weeks as occurs in tourists, trekkers, and mountaineers who visit high altitude and normally reside near sea level. We briefly review the acute physiological adjustments and early acclimatization that occur in the cardiovascular system and the lungs of healthy individuals. These ensure life-sustaining oxygen delivery to the tissues despite a reduction in the partial pressure of inspired oxygen between 20% and 60% at 2500 and 8000 m, respectively. One of the acute adjustments, hypoxic pulmonary vasoconstriction (HPV), may be disadvantageous in those with a vigorous response and lead to 2 potentially lethal illnesses, high-altitude pulmonary edema (HAPE) and subacute mountain sickness (SAMS), which we present in more detail. Finally, on the basis of knowledge about the acute physiological adjustments and acclimatization and, when available, a review of the literature, we discuss the highaltitude tolerance of patients with coronary artery disease, congestive heart failure, arrhythmias, systemic hypertension, and pulmonary hypertension. Effects of Exposure to High Altitude on the Normal Cardiovascular System CirculationThe major effects of acute hypoxia on the heart and lung are shown in Figure 1. Hypoxia directly affects the vascular tone of the pulmonary and systemic resistance vessels and increases ventilation and sympathetic activity via stimulation of the peripheral chemoreceptors. 1 Interactions occur between the direct effects of hypoxia on blood vessels and the chemoreceptor-mediated responses in the systemic and pulmonary circulation. Unraveling the underlying mechanisms of the hypoxic vasodilatation of systemic arterioles is an active area of research. Several mechanisms appear to regulate local oxygen delivery according to the needs of the tissues 2,3 ; for instance, the release of ATP from red blood cells and the generation of NO by various ways appear to regulate local oxygen delivery according to the needs of the tissue. These mechanisms may decrease with prolonged stay at high altitude when oxygen content of the blood increases because of ventilatory acclimatization, an increase in hematocrit associated with plasma volume reduction, and an increase in red blood cell mass due to erythropoiesis.Peripheral chemoreceptor afferent activity rises hyperbolically as hypoxia increases. 4 Ventilation and sympathetic activity are augmented, as demonstrated by increased urinary and plasma concentration of catecholamines 5 and skeletal muscle sympathetic activity. 6 With exposure over days to weeks, the sensitivity of the peripheral chemoreceptors to hypoxia increases, leading to further enhancement of ventilation (ventilatory acclimatization). This presumably also accounts for the further increase of sympathetic activity documented by microneurography after 3 weeks at 5200 m 6 and elevated catecholamines in urine and plasma. 5 As shown in Figure 1, there is antagonism between the direct effects of hypoxia on the resistance vessels ...

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Exaggerated Endothelin Release in High-Altitude Pulmonary Edema

Abstract: These findings 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 altitude.

Cited by 127 publications

References 31 publications

Acute high-altitude sickness

Acute high-altitude sickness

High‐altitude Pulmonary Edema: Review

Effect of Altitude on the Heart and the Lungs

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