Chronic cor pulmonale due to loss of altitude acclimatization (chronic mountain sickness)

Peñaloza, Dante; Sime, Francisco

doi:10.1016/0002-9343(71)90181-1

Cited by 98 publications

(45 citation statements)

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“…[15][16][17] It is now clear that for those not adapted to living at altitude (usually >2,500 m), ascent to and residence at high altitude results in the development of PH, 8,18,19 defined as a resting P PA of ≥25 mmHg, pulmonary vascular remodeling, 7,12 right ventricular hypertrophy, 20 and, in some cases, right ventricular failure. 21,22 What is also clear is that certain populations have genetically adapted to life at altitude, and genomic studies in these groups, coupled with laboratory studies in animal models, have provided insight into some of the mechanisms involved in the pathogenesis of hypoxic PH (HPH).…”

Section: Hypoxic Phmentioning

confidence: 99%

Pulmonary Vascular and Ventricular Dysfunction in the Susceptible Patient (2015 Grover Conference Series)

2016

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Pulmonary blood vessel structure and tone are maintained by a complex interplay between endogenous vasoactive factors and oxygen-sensing intermediaries. Under physiological conditions, these signaling networks function as an adaptive interface between the pulmonary circulation and environmental or acquired perturbations to preserve oxygenation and maintain systemic delivery of oxygen-rich hemoglobin. Chronic exposure to hypoxia, however, triggers a range of pathogenetic mechanisms that include hypoxia-inducible factor 1α (HIF-1α)-dependent upregulation of the vasoconstrictor peptide endothelin 1 in pulmonary endothelial cells. In pulmonary arterial smooth muscle cells, chronic hypoxia induces HIF-1α-mediated upregulation of canonical transient receptor potential proteins, as well as increased Rho kinase-Ca 2+ signaling and pulmonary arteriole synthesis of the profibrotic hormone aldosterone. Collectively, these mechanisms contribute to a contractile or hypertrophic pulmonary vascular phenotype. Genetically inherited disorders in hemoglobin structure are also an important etiology of abnormal pulmonary vasoreactivity. In sickle cell anemia, for example, consumption of the vasodilator and antimitogenic molecule nitric oxide by cell-free hemoglobin is an important mechanism underpinning pulmonary hypertension. Contemporary genomic and transcriptomic analytic methods have also allowed for the discovery of novel risk factors relevant to sickle cell disease, including GALNT13 gene variants. In this report, we review cutting-edge observations characterizing these and other pathobiological mechanisms that contribute to pulmonary vascular and right ventricular vulnerability.Keywords: hypoxia, pulmonary hypertension, genetics. In the autumn of 2015 at the Lost Valley Ranch in Sedalia, Colorado, the 34th Grover Conference, on pulmonary circulation in the "omics" era, convened for a 4-day symposium to discuss contemporary scientific concepts in the genetics, genomics, proteomics, and epigenetics of pulmonary vascular diseases. This biannual meeting, sponsored by the American Thoracic Society and co-led this year by Drs. C. Gregory Elliot, Wendy K. Chung, D. Hunter Best, and Eric D. Austin, commemorates the perpetual and transformative scientific contributions of Dr. Robert Grover 1 to the fields of high-altitude medicine and pulmonary vascular disease. This review is part of an ongoing Pulmonary Circulation thematic series that aims to provide a synopsis of key concepts presented at this year's Grover Conference.Here, we summarize the discussions that constituted a section of the conference emphasizing novel genetic and molecular mechanisms underpinning "pulmonary vascular and ventricular dysfunction in the susceptible patient." To accomplish this, three concepts are reviewed in detail: the functional relevance of chronic hypoxia (CH), discovered through genomic analyses; novel molecular mechanisms and phenotypic signatures of pulmonary vascular disease in sickle cell disease; and hormonal regulation of vascular f...

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Section: Hypoxic Phmentioning

confidence: 99%

Pulmonary Vascular and Ventricular Dysfunction in the Susceptible Patient (2015 Grover Conference Series)

2016

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“…Data derived from AriasStella and Saldaña, 13 Arias-Stella and Castillo, 14 Penaloza et al, 15 and Arias-Stella 16 . tion, so that mild or moderate increases of altitude above 3000 m are associated with important changes of SaO 2 and PAP ( Figure 4A and 4B 26 Higher PPA values between 23 and 28 mm Hg and SaO 2 values between 78% and 81% have been described in Chengdou in Qinghai, China, located at Ϸ4000 m, 27 and in Andean towns of Morococha and Cerro de Pasco, located at Ͼ4000 m (Table 3). 8,28 There are 2 remarkable exceptions to the relation of altitude to PAP ( Figure 4A). An unexpectedly high degree of PH was found at 3100 m in Leadville, Colo, in native adolescents of European ancestry and relative newcomers to HA.…”

Section: Pap Arterial Oxygen Saturation and Level Of Altitudementioning

confidence: 95%

“…38 Rotta et al were the first to describe PH in 1 case of CMS, 17 and then Penaloza et al, who worked at Cerro de Pasco, Peru (4340 m), carried out investigations on the heart and pulmonary circulation in 10 patients with CMS. 28,54 Afterward, Bolivian investigators reported 2 studies. 55,56 Further cardiac catheterization studies on CMS have not been performed in the Andean region.…”

Section: Chronic Mountain Sicknessmentioning

confidence: 99%

“…Clinical and hemodynamic studies were performed in these patients and the results were compared with a group of healthy natives who resided at the same altitude. 28,54 Respiratory studies have been published by Peruvian and North American investigators. 65,66 In recent decades Asian investigators studied a great number of patients with CMS and described a clinical picture 67,68 that closely resembles the classic description by Peruvian investigators.…”

Section: Clinical Picture Of Cmsmentioning

confidence: 99%

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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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“…The basic pathogenic mechanism in this type of chronic mountain sickness is a failure of homeostatic adjustment to the atmosphere at high altitude. Since Monge (1943) (Monge, 1928;Hurtado, 1942;Pefialoza and Sime, 1971) and have been attributed to a decreased sensitivity of the respiratory centre to carbon dioxide and/ or of the chemoreceptors to hypoxaemia. This leads to hypoventilation and thus to increasing systemic arterial unsaturation.…”

mentioning

confidence: 99%