scholarly journals Long-term chronic intermittent hypoxia: a particular form of chronic high-altitude pulmonary hypertension

2020 ◽  
Vol 10 (1_suppl) ◽  
pp. 5-12
Author(s):  
Julio Brito ◽  
Patricia Siques ◽  
Eduardo Pena
Keyword(s):  
Pulmonary Hypertension ◽  
High Altitude ◽  
Hypobaric Hypoxia ◽  
Intermittent Hypoxia ◽  
Clinical Presentation ◽  
Chronic Intermittent Hypoxia ◽  
Chronic Mountain Sickness ◽  
Epidemiological Pattern ◽  
Mountain Sickness

In some subjects, high-altitude hypobaric hypoxia leads to high-altitude pulmonary hypertension. The threshold for the diagnosis of high-altitude pulmonary hypertension is a mean pulmonary artery pressure of 30 mmHg, even though for general pulmonary hypertension is ≥25 mmHg. High-altitude pulmonary hypertension has been associated with high hematocrit findings (chronic mountain sickness), and although these are two separate entities, they have a synergistic effect that should be considered. In recent years, a new condition associated with high altitude was described in South America named long-term chronic intermittent hypoxia and has appeared in individuals who commute to work at high altitude but live and rest at sea level. In this review, we discuss the initial epidemiological pattern from the early studies done in Chile, the clinical presentation and possible molecular mechanism and a discussion of the potential management of this condition.

scholarly journals Involvement of overweight and lipid metabolism in the development of pulmonary hypertension under conditions of chronic intermittent hypoxia

2020 ◽  
Vol 10 (1_suppl) ◽  
pp. 42-49
Author(s):  
Patricia Siques ◽  
Julio Brito ◽  
Stefany Ordenes ◽  
Eduardo Pena
Keyword(s):  
Pulmonary Hypertension ◽  
Lipid Metabolism ◽  
High Altitude ◽  
Intermittent Hypoxia ◽  
Acute Mountain Sickness ◽  
Overweight And Obesity ◽  
Chronic Intermittent Hypoxia ◽  
Inflammatory Status ◽  
Mountain Sickness

There is growing evidence that exposure to hypoxia, regardless of the source, elicits several metabolic responses in individuals. These responses are constitutive and are usually observed under hypoxia but vary according to the type of exposure. The aim of this review was to describe the involvement of obesity and lipid metabolism in the development of high-altitude pulmonary hypertension and in the development of acute mountain sickness under chronic intermittent hypoxia. Overweight or obesity, which are common in individuals with long-term chronic intermittent hypoxia exposure (high-altitude miners, shift workers, and soldiers), are thought to play a major role in the development of acute mountain sickness and high-altitude pulmonary hypertension. This association may be rooted in the interactions between obesity-related metabolic and physical alterations, such as increased waist circumference and neck circumference, among others, which lead to critical ventilation impairments; these impairments aggravate hypoxemia at high altitude, thereby triggering high-altitude diseases. Overweight and obesity are strongly associated with higher mean pulmonary artery pressure in the context of long-term chronic intermittent hypoxia. Remarkably, de novo synthesis of triglycerides by the sterol regulatory element-binding protein-1c pathway has been demonstrated, mainly due to the upregulation of stearoyl-CoA desaturase-1, which is also associated with the same outcomes. Therefore, overweight, obesity, and other metabolic conditions may hinder proper acclimatization. The involved mechanisms include respiratory impairment, alteration of the nitric oxide pathways, inflammatory status, reactive oxygen species imbalance, and other metabolic changes; however, further studies are required.

scholarly journals Thin Air Resulting in High Pressure: Mountain Sickness and Hypoxia-Induced Pulmonary Hypertension

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Jan Grimminger ◽  
Manuel Richter ◽  
Khodr Tello ◽  
Natascha Sommer ◽  
Henning Gall ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
High Altitude ◽  
Hypobaric Hypoxia ◽  
Current Knowledge ◽  
Treatment Options ◽  
Acute Response ◽  
Mechanisms Of Adaptation ◽  
Mountain Sickness

With rising altitude the partial pressure of oxygen falls. This phenomenon leads to hypobaric hypoxia at high altitude. Since more than 140 million people permanently live at heights above 2500 m and more than 35 million travel to these heights each year, understanding the mechanisms resulting in acute or chronic maladaptation of the human body to these circumstances is crucial. This review summarizes current knowledge of the body’s acute response to these circumstances, possible complications and their treatment, and health care issues resulting from long-term exposure to high altitude. It furthermore describes the characteristic mechanisms of adaptation to life in hypobaric hypoxia expressed by the three major ethnic groups permanently dwelling at high altitude. We additionally summarize current knowledge regarding possible treatment options for hypoxia-induced pulmonary hypertension by reviewing in vitro, rodent, and human studies in this area of research.

scholarly journals Association of Genes of the NO Pathway with Altitude Disease and Hypoxic Pulmonary Hypertension

2021 ◽  
Vol 10 (24) ◽  
pp. 5761
Author(s):  
Juliane Hannemann ◽  
Patricia Siques ◽  
Lena Schmidt-Hutten ◽  
Julia Zummack ◽  
Julio Brito ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
High Altitude ◽  
Intermittent Hypoxia ◽  
Acute Mountain Sickness ◽  
Genomic Variation ◽  
Chronic Intermittent Hypoxia ◽  
Plasma Adma ◽  
Major Allele ◽  
Mountain Sickness

Chronic intermittent hypoxia leads to high-altitude pulmonary hypertension, which is associated with high asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis. Therefore, we aimed to understand the relation of single nucleotide polymorphisms in this pathway to high-altitude pulmonary hypertension (HAPH). We genotyped 69 healthy male Chileans subjected to chronic intermittent hypoxia. Acclimatization to altitude was determined using the Lake Louise Score and the presence of acute mountain sickness. Echocardiography was performed after six months in 24 individuals to estimate pulmonary arterial pressure. The minor allele of dimethylarginine dimethylaminohydrolase (DDAH)1 rs233112 was associated with high-baseline plasma ADMA concentration, while individuals homozygous for the major allele of DDAH2 rs805304 had a significantly greater increase in ADMA during chronic intermittent hypoxia. The major allele of alanine glyoxylate aminotransferase-2 (AGXT2) rs37369 was associated with a greater reduction of plasma symmetric dimethylarginine (SDMA). Several genes were associated with high-altitude pulmonary hypertension, and the nitric oxide synthase (NOS)3 and DDAH2 genes were related to acute mountain sickness. In conclusion, DDAH1 determines baseline plasma ADMA, while DDAH2 modulates ADMA increase in hypoxia. AGXT2 may be up-regulated in hypoxia. Genomic variation in the dimethylarginine pathway affects the development of HAPH and altitude acclimatization.

Role of sex hormones in development of chronic mountain sickness in rats

1994 ◽  
Vol 77 (1) ◽  
pp. 427-433 ◽  
Author(s):  
L. C. Ou ◽  
G. L. Sardella ◽  
J. C. Leiter ◽  
T. Brinck-Johnsen ◽  
R. P. Smith
Keyword(s):  
Gender Differences ◽  
Pulmonary Hypertension ◽  
High Altitude ◽  
Sex Hormones ◽  
Systolic Pressure ◽  
Female Rats ◽  
Hypoxic Exposure ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness

After chronic exposure to hypoxia, Hilltop Sprague-Dawley rats developed excessive polycythemia and severe pulmonary hypertension and right ventricular (RV) hypertrophy, signs consistent with human chronic mountain sickness; however, there were gender differences in the magnitude of the polycythemia and susceptibility to the fatal consequence of chronic mountain sickness. Orchiectomy and ovariectomy were performed to evaluate the role of sex hormones in the gender differences in these hypoxic responses. After 40 days of exposure to simulated high altitude (5,500 m; barometric pressure of 370 Torr and inspired Po2 of 73 Torr), both sham-gonadectomized male and female rats developed polycythemia and had increased RV peak systolic pressure and RV hypertrophy. The hematocrit was slightly but significantly higher in males than in females. Orchiectomy did not affect these hypoxic responses, although total ventricular weight was less in the castrated high-altitude rats. At high altitude, the mortality rates were 67% in the sham-operated male rats and 50% in the castrated animals. In contrast, ovariectomy aggravated the high-altitude-associated polycythemia and increased RV peak systolic pressure and RV weight compared with the sham-operated high-altitude female rats. Both sham-operated control and ovariectomized females suffered negligible mortality at high altitude. The present study demonstrated that 1) the male sex hormones play no role in the development of the excessive polycythemia, pulmonary hypertension, and RV hypertrophy during chronic hypoxic exposure or in the associated high mortality and 2) the female sex hormones suppressed both the polycythemic and cardiopulmonary responses in vivo during chronic hypoxic exposure.

scholarly journals Reversal of Pulmonary Hypertension in a Patient with Chronic Mountain Sickness after Relocation to Low Altitude

2021 ◽  
Author(s):  
Abdirashit Maripov ◽  
Kubatbek Muratali Uulu ◽  
Samatbek Satybaldyev ◽  
Nadira Kushubakova ◽  
Akpay Sarybaev
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricle ◽  
Complete Resolution ◽  
Laboratory Examination ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness ◽  
Low Altitude ◽  
Pulmonary Artery Diameter

Long-term high altitude residence can be complicated by development of Chronic Mountain Sickness (CMS) characterised by excessive erythrocytosis and neurological symptoms. In some patients, CMS may be associated with various degrees of Pulmonary Hypertension (PH). There have been no reports on changes in the pulmonary circulation and Right Ventricular (RV) structure following translocation to low altitude of patients with CMS. Here the authors report a case of 56 years old female patient, resident of Sary Mogol (3,000 m, Kyrgyzstan), diagnosed of CMS on clinical and laboratory examination. Transthoracic echocardiography revealed slightly dilated Right ventricle and significantly enlarged Pulmonary Artery diameter was found. The patient undergone complete resolution of symptoms and alleviation of PH within three years of residence at low altitude. Thus, relocation to low altitude cures CMS and reverses PH.

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