Pulmonary Hypertension on Exertion in Normal Man Living at 10,150 Feet (Leadville, Colorado)

Vogel, John H.K.; Weaver, Walt F.; Rose, Raymond L.; Blount, S. Gilbert; Grover, Robert F.

doi:10.1159/000192254

Cited by 39 publications

(7 citation statements)

References 10 publications

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“…Although the average PAP levels in the high altitude populations are higher than those in sea level residents, there is marked variability in PAP values among highlanders [17,185,197,198], suggesting that not all individuals are prone to PAP elevation at high altitude. Thus, while most highlanders display mild-to-moderate PAP elevation, some high altitude dwellers may have PAP values that are not different from those in sea level residents, and others may develop severe pulmonary hypertension.…”

Section: Pulmonary Circulation In Healthy High Altitude Residentsmentioning

confidence: 90%

“…A significant variation in the pulmonary vascular response to acute hypoxia has been demonstrated both between and within species [6,15]. In humans, the individual acute HPV also varies significantly [15][16][17].…”

Section: Hypoxic Pulmonary Vasoconstrictionmentioning

confidence: 99%

“…This dependence is not linear and applicable to many other high altitude populations [5]. PAP levels remain unchanged below 2000 m [7] and slightly increase up to 3000 m [17,[193][194][195]. Above 3000 m, PAP increases more markedly with altitude [192].…”

Section: Pulmonary Circulation In Healthy High Altitude Residentsmentioning

confidence: 99%

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Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

Sydykov

Mamazhakypov

Maripov

et al. 2021

IJERPH

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Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring at high altitudes in non-acclimatized healthy individuals. Despite a strong physiologic rationale for using vasodilators for prevention and treatment of HAPE, no systematic studies of their efficacy have been conducted to date. Calcium-channel blockers are currently recommended for drug prophylaxis in high-risk individuals with a clear history of recurrent HAPE based on the extensive clinical experience with nifedipine in HAPE prevention in susceptible individuals. Chronic exposure to hypoxia induces pulmonary vascular remodeling and development of pulmonary hypertension, which places an increased pressure load on the right ventricle leading to right heart failure. Further, pulmonary hypertension along with excessive erythrocytosis may complicate chronic mountain sickness, another high altitude maladaptation disorder. Importantly, other causes than hypoxia may potentially underlie and/or contribute to pulmonary hypertension at high altitude, such as chronic heart and lung diseases, thrombotic or embolic diseases. Extensive clinical experience with drugs in patients with pulmonary arterial hypertension suggests their potential for treatment of high altitude pulmonary hypertension. Small studies have demonstrated their efficacy in reducing pulmonary artery pressure in high altitude residents. However, no drugs have been approved to date for the therapy of chronic high altitude pulmonary hypertension. This work provides a literature review on the role of pulmonary hypertension in the pathogenesis of acute and chronic high altitude maladaptation disorders and summarizes current knowledge regarding potential treatment options.

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Section: Pulmonary Circulation In Healthy High Altitude Residentsmentioning

confidence: 90%

Section: Hypoxic Pulmonary Vasoconstrictionmentioning

confidence: 99%

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Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

Sydykov

Mamazhakypov

Maripov

et al. 2021

IJERPH

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“…Also notable was that, with exercise, many of the subjects had significant increases in mPAP that were exaggerated in comparison to subjects at sea level. 25 Interestingly, one of the subjects with particularly severe PH in this study relocated to sea level, and after 11 months underwent repeat right heart catheterization, demonstrating normalization of resting Ppa . 26 This reversibility was further studied by the South American group, where Sime et al 27 studied the effects of relocating high-altitude natives to Lima.…”

Section: Parallel Science In the Rocky Mountainsmentioning

confidence: 66%

From the Andes to the Rocky Mountains: A Historical View of High-Altitude Pulmonary Hypertension

Chang

Robinson

2020

Advances in Pulmonary Hypertension

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The current understanding of high-altitude pulmonary hypertension (HAPH) is largely attributable to the work of a small cadre of international scientists. The present article discusses the discovery and early investigations into HAPH that now serve as the foundation of our modern understanding of the disease. Further, though HAPH is clearly a distinct entity, we highlight how this early work led to a broader understanding of pulmonary vascular disease—including pulmonary arterial hypertension (PAH)—through the development of translational clinical models of disease, elucidation of hypoxic signaling, and therapeutics applicable to PAH.

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“…These adaptive responses are related to increased expression of erythropoietin (EPO) and Cu-uptake transporter1 (CTR1) genes, respectively. The chronic upregulation of such genes can, then, favor the development of pulmonary hypertension (155)(156)(157). Other maladaptive conditions are seen in newborns where birthweight is inversely related to the altitude (the higher the altitude, lower the birthweight), and the higher prevalence of maternal hypertension and preeclampsia in highlanders (158)(159)(160).…”

Section: Chronic Hypoxic Statesmentioning

confidence: 99%

Hypoxia Inducible Factors as Central Players in the Pathogenesis and Pathophysiology of Cardiovascular Diseases

Rojas

Villanueva

Bond

2021

Front. Cardiovasc. Med.

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Cardiovascular (CV) diseases are the major cause of death in industrialized countries. The main function of the CV system is to deliver nutrients and oxygen to all tissues. During most CV pathologies, oxygen and nutrient delivery is decreased or completely halted. Several mechanisms, including increased oxygen transport and delivery, as well as increased blood flow are triggered to compensate for the hypoxic state. If the compensatory mechanisms fail to sufficiently correct the hypoxia, irreversible damage can occur. Thus, hypoxia plays a central role in the pathogenesis and pathophysiology of CV diseases. Hypoxia inducible factors (HIFs) orchestrate the gene transcription for hundreds of proteins involved in erythropoiesis, glucose transport, angiogenesis, glycolytic metabolism, reactive oxygen species (ROS) handling, cell proliferation and survival, among others. The overall regulation of the expression of HIF-dependent genes depends on the severity, duration, and location of hypoxia. In the present review, common CV diseases were selected to illustrate that HIFs, and proteins derived directly or indirectly from their stabilization and activation, are related to the development and perpetuation of hypoxia in these pathologies. We further classify CV diseases into acute and chronic hypoxic states to better understand the temporal relevance of HIFs in the pathogenesis, disease progression and clinical outcomes of these diseases. We conclude that HIFs and their derived factors are fundamental in the genesis and progression of CV diseases. Understanding these mechanisms will lead to more effective treatment strategies leading to reduced morbidity and mortality.

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Pulmonary Hypertension on Exertion in Normal Man Living at 10,150 Feet (Leadville, Colorado)

Cited by 39 publications

References 10 publications

Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

From the Andes to the Rocky Mountains: A Historical View of High-Altitude Pulmonary Hypertension

Hypoxia Inducible Factors as Central Players in the Pathogenesis and Pathophysiology of Cardiovascular Diseases

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