Pulmonary hypertension in children born and living at high altitudes

Sime, Francisco; Banchero, Natalio; Peñaloza, Dante; Gamboa, Raul; Cruz, Julio C.; Marticorena, Emilio

doi:10.1016/0002-9149(63)90054-7

Cited by 147 publications

(53 citation statements)

References 19 publications

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“…There is prompt vascular remodeling in infants born at SL by contrast with a delayed process in infants born at HA. Data derived from Penaloza et al, 6 Sime et al, 7 Penaloza et al, 8 Gamboa and Maticorena, 9 Arias-Stella and Saldaña, 13 Arias-Stella and Castillo, 14 Penaloza et al, 15 and Arias-Stella 16 . 3A, and 3B).…”

Section: Pathogenesis Of Human Chronic Hypoxic Pulmonary Hypertensionmentioning

confidence: 99%

The Heart and Pulmonary Circulation at High Altitudes

2007

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Abstract-More than 140 million people worldwide live Ͼ2500 m above sea level. Of them, 80 million live in Asia, and 35 million live in the Andean mountains. This latter region has its major population density living above 3500 m. The primary objective of the present study is to review the physiology, pathology, pathogenesis, and clinical features of the heart and pulmonary circulation in healthy highlanders and patients with chronic mountain sickness. A systematic review of worldwide literature was undertaken, beginning with the pioneering work done in the Andes several decades ago. Original articles were analyzed in most cases and English abstracts or translations of articles written in Chinese were reviewed. Pulmonary hypertension in healthy highlanders is related to a delayed postnatal remodeling of the distal pulmonary arterial branches. The magnitude of pulmonary hypertension increases with the altitude level and the degree of exercise. There is reversal of pulmonary hypertension after prolonged residence at sea level. Chronic mountain sickness develops when the capacity for altitude adaptation is lost. These patients have moderate to severe pulmonary hypertension with accentuated hypoxemia and exaggerated polycythemia. The clinical picture of chronic mountain sickness differs from subacute mountain sickness and resembles other chronic altitude diseases described in China and Kyrgyzstan. The heart and pulmonary circulation in healthy highlanders have distinct features in comparison with residents at sea level. Chronic mountain sickness is a public health problem in the Andean mountains and other mountainous regions around the world. Therefore, dissemination of preventive and therapeutic measures is essential. Key Words: altitude Ⅲ altitude sickness Ⅲ hypertension, pulmonary P eople native to high altitude (HA) environments live in an environment of hypobaric hypoxia with low ambient partial pressure of oxygen. As a consequence, they develop alveolar hypoxia, hypoxemia, and polycythemia. Despite this, healthy highlanders are able to perform physical activities similar to and often even more strenuous than those of people living at sea level (SL). This phenomenon has been ascribed to adaptive mechanisms that occur at sequential steps of the oxygen transport system with the main purpose of decreasing the total pO 2 gradient from ambient hypoxic air to mixed venous blood at the tissue level.The heart and pulmonary circulation in healthy people living at HA exhibit important physiological and anatomic characteristics, which resemble those that occur in chronic clinical conditions associated with alveolar hypoxia, hypoxemia, and polycythemia. Healthy HA natives have pulmonary hypertension (PH), right ventricular hypertrophy (RVH) and increased amount of smooth muscle cells (SMCs) in the distal pulmonary arterial branches. All these findings become exaggerated when healthy highlanders lose their capacity for adaptation and develop chronic mountain sickness (CMS). The physiological, pathological, pathogenic, and cl...

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Section: Pathogenesis Of Human Chronic Hypoxic Pulmonary Hypertensionmentioning

confidence: 99%

The Heart and Pulmonary Circulation at High Altitudes

2007

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“…Pulmonary haemodynamic measurements performed in children and young adults show persistence of elevated Ppa at high altitude for weeks, months or years [36]. Performance of right heart catheterisation was reported in Han Chinese subjects who developed HAPH after residing in Lhasa at an elevation 3,658 m for 11-36 yrs, as well as in Andes natives residing at an elevation of ,4,300 m [32].…”

Section: Right Heart Catheterisationmentioning

confidence: 99%

High-altitude pulmonary hypertension: Table. 1—

Xq¹,

Jing²

2009

Eur Respir Rev

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High-altitude pulmonary hypertension (HAPH) is a specific disease affecting populations that live at high elevations. The prevalence of HAPH among those residing at high altitudes needs to be further defined. Whereas reduction in nitric oxide production may be one mechanism for the development of HAPH, the roles of endothelin-1 and prostaglandin I 2 pathways in the pathogenesis of HAPH deserve further study.Although some studies have suggested that genetic factors contribute to the pathogenesis of HAPH, data published to date are insufficient for the identification of a significant number of gene polymorphims in HAPH.The clinical presentation of HAPH is nonspecific. Exertional dyspnoea is the most common symptom and signs related to right heart failure are common in late stages of HAPH. Echocardiography is the most useful screening tool and right heart catheterisation is the gold standard for the diagnosis of HAPH. The ideal management for HAPH is migration to lower altitudes. Phosphodiesterase 5 is an attractive drug target for the treatment of HAPH.In addition, acetazolamide is a promising therapeutic agent for high-altitude pulmonary hypertension. To date, no evidence has confirmed whether endothelin-receptor antagonists have efficacy in the treatment of high-altitude pulmonary hypertension.KEYWORDS: High-altitude pulmonary hypertension, hypoxia-inducible factor-1, nitric oxide, phosphodiesterase inhibitors, pulmonary vasoconstriction, right heart catheterisation H igh-altitude pulmonary hypertension (HAPH) due to chronic exposure to high altitude is a designated subset of pulmonary hypertension (PH) according to the third clinical classification of PH, which was approved during a conference in 2003 in Venice, Italy [1].It is estimated that more than 140 million people live 2,500 m above sea level, and the number of temporary visitors to mountains is close to 40 million [2,3]. Due to the substantial population exposed to the effects of high altitude, HAPH has become a public health problem in mountainous regions throughout the world. There are three specific locations where high-altitude studies have recently been performed: 1) the Himalayas of Asia; 2) the Andes of South America; and 3) the Rocky Mountains of North America. The present review will focus on the epidemiology, pathophysiology, pathogenesis, clinical characteristics and treatment of HAPH. DEFINITIONHAPH is a clinical syndrome seen in adults and children residing in high-altitude regions. As chronic mountain syndrome (CMS) is characterised by severe hypoxaemia, excessive polycythaemia and marked PH [4], HAPH is regarded as an important subset of CMS. However, the definition and diagnostic criteria of HAPH remain somewhat vague. According to the 2003 conference on PH, HAPH is classified in the third group of PH (table 1) [1]. Thus, right heart catheterisation is required to establish the diagnosis of HAPH (PH is defined by a mean pulmonary artery pressure (P pa) of .25 mmHg at rest or .30 mmHg with exercise) [5]. EPIDEMIOLOGYAlthough HAP...

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“…It has been reported that infants born at altitudes between 3,500-4,500 m may show persistent near systemic PAP values for some time after birth [43], and that in some cases elevated mean PAP (y40 mmHg) persisted during infancy [44]. These observations may be linked to right heart failure in infants after birth [8] and to chronic high-altitude pulmonary hypertension in adulthood [45].…”

Section: Effects Of Chronic Exposure To High Altitudementioning

confidence: 99%

“…Pulmonary haemodynamic measurements performed in children and young adults show persistence of elevated PAP at high altitude for weeks, months or years [44,54]. Histological examination of the pulmonary vessels in high-altitude residents, who died from causes other than CMS, show persistence of the typical foetal patterns (thickened media) [45,55].…”

Section: High-altitude Pulmonary Hypertensionmentioning

confidence: 99%

High-altitude pulmonary hypertension: a pathophysiological entity to different diseases

Maggiorini¹,

León‐Velarde²

2003

Eur Respir J

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High-altitude pulmonary hypertension: a pathophysiological entity to different diseases. M. Maggiorini, F. Léon-Velarde. #ERS Journals Ltd 2003. ABSTRACT: Pulmonary hypertension is a hallmark of high-altitude pulmonary oedema (HAPE) and of congestive right heart failure in subacute mountain sickness (SMS) and chronic mountain sickness (CMS) in the Himalayas and in the end-stage of CMS (Monge9s disease) in the Andes.There are studies to suggest that transmission of excessively elevated pulmonary artery pressure and/or flow to the pulmonary capillaries leading to alveolar haemorrhage is the pathophysiological mechanism of HAPE.In the Himalayas, HAPE was successfully prevented by extending the acclimatisation period from a few days to 5 weeks, however, this did not prevent the occurrence of congestive right heart failure after several weeks of stay at 6,000 m. This leads to the concept that rapid remodelling of the small precapillary arteries prevents HAPE but not the development of right heart failure in SMS and CMS.Unresponsiveness of pulmonary hypertension to oxygen at high altitude and its complete resolution only after weeks of stay at low altitude suggest that structural rather than functional changes are its pathophysiological mechanism. Since pulmonary hypertension at high altitude is the driving force leading to high-altitude pulmonary oedema and "high-altitude right heart failure" in newcomers and residents of high altitude, the authors propose to adjust current terminology accordingly. The physiological response of the pulmonary circulation to hypobaric and normobaric hypoxia is to increase pulmonary arteriolar resistance. The magnitude of hypoxic pulmonary vasoconstriction is highly variable between humans, probably based on genetics and adaptive mechanisms. Sites of hypoxic pulmonary vasoconstriction are small pulmonary arterioles and veins of a diameter of v900 mm, the veins accounting for y20% of the total increase in pulmonary vascular resistance caused by hypoxia [1,2]. The structural changes in small pulmonary arteries and veins appear to reflect this genetically based and adaptive process [3][4][5] in humans and animals. Excessive hypoxic pulmonary vasoconstriction, and thus susceptibility to develop a right heart failure within weeks at high altitude, was first described in Colorado cattle [6]. Indian soldiers stationed at an altitude between 5,800-6,700 m [7] and Han infants in Lhasa [8] develop severe congestive right heart failure within weeks or months after arrival at high altitude. An excessively elevated pulmonary artery pressure (PAP) has not only been reported to cause high altitude cor pulmonale within weeks, months, or years in newcomers, but also in high-altitude residents of the Andes and nonacclimatised climbers prone to high-altitude pulmonary oedema (HAPE) [9]. The results of these studies suggest that an excessive rise in PAP is a common denominator in HAPE [9], the syndrome described by SUI et al. [8] in infants and by ANAND et al. [7] in adults at 6,700 m and termed "subacute...

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Pulmonary hypertension in children born and living at high altitudes

Cited by 147 publications

References 19 publications

The Heart and Pulmonary Circulation at High Altitudes

The Heart and Pulmonary Circulation at High Altitudes

High-altitude pulmonary hypertension: Table. 1—

High-altitude pulmonary hypertension: a pathophysiological entity to different diseases

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