Pulmonary hemodynamic response to exercise in subjects with prior high-altitude pulmonary edema

Individuals with a prior history of (susceptible to high altitude pulmonary edema (HAPE-S) have high resting pulmonary arterial pressures, but little data are available on their vascular response to exercise. We studied the pulmonary vascular response to exercise in seven HAPE-S and nine control subjects at sea level and at 3,810 m altitude. At each location, both normoxic (inspired PO2 = 148 Torr) and hypoxic (inspired PO2 = 91 Torr) studies were conducted. Pulmonary hemodynamic measurements included pulmonary arterial and pulmonary arterial occlusion pressures. A multiple regression analysis demonstrated that the pulmonary arterial pressure reactivity to exercise was significantly greater in the HAPE-S group. This reactivity was not influenced by altitude or oxygenation, implying that the response was intrinsic to the pulmonary circulation. Pulmonary arterial occlusion pressure reactivity to exercise was also greater in the HAPE-S group, increasing with altitude but independent of oxygenation. These findings suggest an augmented flow-dependent pulmonary vasoconstriction and/or a reduced vascular cross-sectional area in HAPE-S subjects.

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Pulmonary arterial systolic pressure and susceptibility to high altitude pulmonary edema

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2011.09.011 ◽

2011 ◽

Vol 179 (2-3) ◽

pp. 294-299 ◽

Cited By ~ 5

Author(s):

Rémi Mounier ◽

Aimé Amonchot ◽

Nicolas Caillot ◽

Cécile Gladine ◽

Bernard Citron ◽

...

Keyword(s):

Pulmonary Edema ◽

High Altitude ◽

Systolic Pressure ◽

Arterial Systolic Pressure ◽

Pulmonary Arterial Systolic Pressure ◽

High Altitude Pulmonary Edema ◽

Pulmonary Arterial

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P458Changes of pulmonary vasoactive factors and its relation with pulmonary arterial hypertension in patients with high altitude pulmonary edema

Cardiovascular Research ◽

10.1093/cvr/cvu091.136 ◽

2014 ◽

Vol 103 (suppl 1) ◽

pp. S84.2-S84

Author(s):

Q Zhou

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Pulmonary Edema ◽

High Altitude ◽

Vasoactive Factors ◽

High Altitude Pulmonary Edema ◽

Pulmonary Arterial

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Increased hepcidin levels in high-altitude pulmonary edema

Journal of Applied Physiology ◽

10.1152/japplphysiol.00940.2014 ◽

2015 ◽

Vol 118 (3) ◽

pp. 292-298 ◽

Cited By ~ 9

Author(s):

Sandro Altamura ◽

Peter Bärtsch ◽

Christoph Dehnert ◽

Marco Maggiorini ◽

Günter Weiss ◽

...

Keyword(s):

Pulmonary Edema ◽

High Altitude ◽

Serum Iron ◽

Hypoxic Pulmonary Vasoconstriction ◽

Iron Availability ◽

Hepcidin Expression ◽

High Altitude Pulmonary Edema ◽

Pulmonary Arterial ◽

Short Time ◽

Inappropriate Expression

Low iron availability enhances hypoxic pulmonary vasoconstriction (HPV). Considering that reduced serum iron is caused by increased erythropoiesis, insufficient reabsorption, or elevated hepcidin levels, one might speculate that exaggerated HPV in high-altitude pulmonary edema (HAPE) is related to low serum iron. To test this notion we measured serum iron and hepcidin in blood samples obtained in previously published studies at low altitude and during 2 days at 4,559 m (HA1, HA2) from controls, individuals with HAPE, and HAPE-susceptible individuals where prophylactic dexamethasone and tadalafil prevented HAPE. As reported, at 4,559 m pulmonary arterial pressure was increased in healthy volunteers but reached higher levels in HAPE. Serum iron levels were reduced in all groups at HA2. Hepcidin levels were reduced in all groups at HA1 and HA2 except in HAPE, where hepcidin was decreased at HA1 but unexpectedly high at HA2. Elevated hepcidin in HAPE correlated with increased IL-6 at HA2, suggesting that an inflammatory response related to HAPE contributes to increased hepcidin. Likewise, platelet-derived growth factor, a regulator of hepcidin, was increased at HA1 and HA2 in controls but not in HAPE, suggesting that hypoxia-controlled factors that regulate serum iron are inappropriately expressed in HAPE. In summary, we found that HAPE is associated with inappropriate expression of hepcidin without inducing expected changes in serum iron within 2 days at HA, likely due to too short time. Although hepcidin expression is uncoupled from serum iron availability and hypoxia in individuals developing HAPE, our findings indicate that serum iron is not related with exaggerated HPV.

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Susceptibility to high-altitude pulmonary edema is associated with increased pulmonary arterial stiffness during exercise

Journal of Applied Physiology ◽

10.1152/japplphysiol.00153.2019 ◽

2020 ◽

Vol 128 (3) ◽

pp. 514-522

Author(s):

A. Mulchrone ◽

H. Moulton ◽

M. W. Eldridge ◽

N. C. Chesler

Keyword(s):

Arterial Stiffness ◽

Pulmonary Edema ◽

High Altitude ◽

Sea Level ◽

Published Data ◽

Control Subjects ◽

High Altitude Pulmonary Edema ◽

Artery Stiffness ◽

Response To Exercise ◽

Distal Artery

High-altitude pulmonary edema (HAPE), a reversible form of capillary leak, is a common consequence of rapid ascension to high altitude and a major cause of death related to high-altitude exposure. Individuals with a prior history of HAPE are more susceptible to future episodes, but the underlying risk factors remain uncertain. Previous studies have shown that HAPE-susceptible subjects have an exaggerated pulmonary vasoreactivity to acute hypoxia, but incomplete data are available regarding their vascular response to exercise. To examine this, seven HAPE-susceptible subjects and nine control subjects (HAPE-resistant) were studied at rest and during incremental exercise at sea level and at 3,810 m altitude. Studies were conducted in both normoxic (inspired Po2 = 148 Torr) and hypoxic (inspired Po2 = 91 Torr) conditions at each location. Here, we report an expanded analysis of previously published data, including a distensible vessel model that showed that HAPE-susceptible subjects had significantly reduced small distal artery distensibility at sea level compared with HAPE-resistant control subjects [0.011 ± 0.001 vs. 0.021 ± 0.002 mmHg−1; P < 0.001). Moreover, HAPE-susceptible subjects demonstrated constant distensibility over all conditions, suggesting that distal arteries are maximally distended at rest. Consistent with having increased distal artery stiffness, HAPE-susceptible subjects had greater increases in pulmonary artery pulse pressure with exercise, which suggests increased proximal artery stiffness. In summary, HAPE-susceptible subjects have exercise-induced increases in proximal artery stiffness and baseline increases in distal artery stiffness, suggesting increased pulsatile load on the right ventricle. NEW & NOTEWORTHY In comparison to subjects who appear resistant to high-altitude pulmonary edema, those previously symptomatic show greater increases in large and small artery stiffness in response to exercise. These differences in arterial stiffness may be a risk factor for the development of high-altitude pulmonary edema or evidence that consequences of high-altitude pulmonary edema are long-lasting after return to sea level.

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Acute Hypoxic Pulmonary Vascular Response Does Not Accompany Plasma Endothelin-1 Elevation in Subjects Susceptible to High Altitude Pulmonary Edema.

Internal Medicine ◽

10.2169/internalmedicine.35.257 ◽

1996 ◽

Vol 35 (4) ◽

pp. 257-260 ◽

Cited By ~ 4

Author(s):

Yunden DROMA ◽

Ge RI-LI ◽

Masao TANAKA ◽

Tomonobu KOIZUMI ◽

Masayuki HANAOKA ◽

...

Keyword(s):

Pulmonary Edema ◽

High Altitude ◽

Vascular Response ◽

Endothelin 1 ◽

High Altitude Pulmonary Edema

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Exercise Responses to Metabolic Function on High Altitude Pulmonary Edema Susceptible Individuals

Defence Life Science Journal ◽

10.14429/dlsj.3.12908 ◽

2018 ◽

Vol 3 (3) ◽

pp. 224

Author(s):

Kaushik Halder ◽

RK Gupta ◽

Anjana Pathak ◽

Montu Saha

Keyword(s):

Pulmonary Edema ◽

High Altitude ◽

Sea Level ◽

Past History ◽

Minute Ventilation ◽

Metabolic Responses ◽

Prior History ◽

High Altitude Pulmonary Edema ◽

History Of ◽

Exercise Induced

The study was aimed to evaluate and compare resting and exercise induced metabolic responses between acclimatized high altitude pulmonary edema (HAPE) susceptible (HAPE-s) and HAPE resistance (HAPE-r) volunteers at sea level. A group of 14 Indian soldiers volunteered for this study, divided into two groups, (i) HAPE-s, with past history of HAPE [n1 = 7; age = 33.3 ± 4.5 (M ± SD)] and (ii) HAPE-r, with prior history of repeated exposure to high altitude and without suffering HAPE [n2 = 7; age = 31.9 ± 4.2 (M ± SD)]. Respiratory frequency (fR), tidal volume (T), minute ventilation (E), oxygen consumption (O2), carbon dioxide output (CO2), heart rate (HR) and respiratory quotient (RQ) were recorded on all the volunteers during resting and exercise conditions. Ventilatory equivalent for oxygen (EqO2) and oxygen pulse (O2P) were calculated. Significant differences were observed between HAPE-s and HAPE-r volunteers in fRrest (25.3% higher), O2Prest (23.7% lower), Emax (50.9% lower) (all P<0.05), fRmax (55.7% lower), O2max (55.5% lower), O2Pmax (34.2% lower) (all P<0.01) and CO2max (42.1% lower, P<0.001). Rest of the parameters did not show any significant differences between the study groups. The study revealed that resting and exercise induced metabolic responses of HAPE-r volunteers was better as compared to acclimatized HAPE-s volunteers at sea level.

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