scholarly journals Heterogeneous Perfusion in COVID-19 and High Altitude Pulmonary Edema: A Review of Two Cases Followed by Implications for Hypoxic Pulmonary Vasoconstriction, Thrombosis Development, Ventilation Perfusion Mismatch and Emergence of Treatment Approaches

Cureus ◽  
2020 ◽  
Author(s):  
Isaac Solaimanzadeh
Keyword(s):  
Pulmonary Edema ◽  
High Altitude ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Treatment Approaches ◽  
Pulmonary Vasoconstriction ◽  
High Altitude Pulmonary Edema

Physiological aspects of high-altitude pulmonary edema

2005 ◽  
Vol 98 (3) ◽  
pp. 1101-1110 ◽  
Author(s):  
Peter Bärtsch ◽  
Heimo Mairbäurl ◽  
Marco Maggiorini ◽  
Erik R. Swenson
Keyword(s):  
Pulmonary Edema ◽  
High Altitude ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Right Heart Catheterization ◽  
Lung Edema ◽  
Heart Catheterization ◽  
Edema Formation ◽  
Pulmonary Vasoconstriction ◽  
Large Molecular Weight ◽  
High Altitude Pulmonary Edema

High-altitude pulmonary edema (HAPE) develops in rapidly ascending nonacclimatized healthy individuals at altitudes above 3,000 m. An excessive rise in pulmonary artery pressure (PAP) preceding edema formation is the crucial pathophysiological factor because drugs that lower PAP prevent HAPE. Measurements of nitric oxide (NO) in exhaled air, of nitrites and nitrates in bronchoalveolar lavage (BAL) fluid, and forearm NO-dependent endothelial function all point to a reduced NO availability in hypoxia as a major cause of the excessive hypoxic PAP rise in HAPE-susceptible individuals. Studies using right heart catheterization or BAL in incipient HAPE have demonstrated that edema is caused by an increased microvascular hydrostatic pressure in the presence of normal left atrial pressure, resulting in leakage of large-molecular-weight proteins and erythrocytes across the alveolarcapillary barrier in the absence of any evidence of inflammation. These studies confirm in humans that high capillary pressure induces a high-permeability-type lung edema in the absence of inflammation, a concept first introduced under the term “stress failure.” Recent studies using microspheres in swine and magnetic resonance imaging in humans strongly support the concept and primacy of nonuniform hypoxic arteriolar vasoconstriction to explain how hypoxic pulmonary vasoconstriction occurring predominantly at the arteriolar level can cause leakage. This compelling but as yet unproven mechanism predicts that edema occurs in areas of high blood flow due to lesser vasoconstriction. The combination of high flow at higher pressure results in pressures, which exceed the structural and dynamic capacity of the alveolar capillary barrier to maintain normal alveolar fluid balance.

Exaggerated Hypoxic Pulmonary Vasoconstriction Without Susceptibility to High Altitude Pulmonary Edema

2015 ◽  
Vol 16 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Christoph Dehnert ◽  
Derliz Mereles ◽  
Sebastian Greiner ◽  
Dagmar Albers ◽  
Fabian Scheurlen ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
High Altitude ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vasoconstriction ◽  
High Altitude Pulmonary Edema

scholarly journals Susceptibility to high-altitude pulmonary edema is associated with a more uniform distribution of regional specific ventilation

2017 ◽  
Vol 122 (4) ◽  
pp. 844-852 ◽  
Author(s):  
Michael D. Patz ◽  
Rui C. Sá ◽  
Chantal Darquenne ◽  
Ann R. Elliott ◽  
Amran K. Asadi ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
High Altitude ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Relative Dispersion ◽  
Pulmonary Vasoconstriction ◽  
High Altitude Pulmonary Edema ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
History Of ◽  
Magnetic Resonance Imaging Mri

High-altitude pulmonary edema (HAPE) is a potentially fatal condition affecting high-altitude sojourners. The biggest predictor of HAPE development is a history of prior HAPE. Magnetic resonance imaging (MRI) shows that HAPE-susceptible (with a history of HAPE), but not HAPE-resistant (with a history of repeated ascents without illness) individuals develop greater heterogeneity of regional pulmonary perfusion breathing hypoxic gas (O2 = 12.5%), consistent with uneven hypoxic pulmonary vasoconstriction (HPV). Why HPV is uneven in HAPE-susceptible individuals is unknown but may arise from regionally heterogeneous ventilation resulting in an uneven stimulus to HPV. We tested the hypothesis that ventilation is more heterogeneous in HAPE-susceptible subjects ( n = 6) compared with HAPE-resistant controls ( n = 7). MRI specific ventilation imaging (SVI) was used to measure regional specific ventilation and the relative dispersion (SD/mean) of SVI used to quantify baseline heterogeneity. Ventilation heterogeneity from conductive and respiratory airways was measured in normoxia and hypoxia (O2 = 12.5%) using multiple-breath washout and heterogeneity quantified from the indexes Scond and Sacin, respectively. Contrary to our hypothesis, HAPE-susceptible subjects had significantly lower relative dispersion of specific ventilation than the HAPE-resistant controls [susceptible = 1.33 ± 0.67 (SD), resistant = 2.36 ± 0.98, P = 0.05], and Sacin tended to be more uniform (susceptible = 0.085 ± 0.009, resistant = 0.113 ± 0.030, P = 0.07). Scond was not significantly different between groups (susceptible = 0.019 ± 0.007, resistant = 0.020 ± 0.004, P = 0.67). Sacin and Scond did not change significantly in hypoxia ( P = 0.56 and 0.19, respectively). In conclusion, ventilation heterogeneity does not change with short-term hypoxia irrespective of HAPE susceptibility, and lesser rather than greater ventilation heterogeneity is observed in HAPE-susceptible subjects. This suggests that the basis for uneven HPV in HAPE involves vascular phenomena. NEW & NOTEWORTHY Uneven hypoxic pulmonary vasoconstriction (HPV) is thought to incite high-altitude pulmonary edema (HAPE). We evaluated whether greater heterogeneity of ventilation is also a feature of HAPE-susceptible subjects compared with HAPE-resistant subjects. Contrary to our hypothesis, ventilation heterogeneity was less in HAPE-susceptible subjects and unaffected by hypoxia, suggesting a vascular basis for uneven HPV.

Increased hepcidin levels in high-altitude pulmonary edema

2015 ◽  
Vol 118 (3) ◽  
pp. 292-298 ◽  
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.

Early hours in the development of high-altitude pulmonary edema: time course and mechanisms

2020 ◽  
Vol 128 (6) ◽  
pp. 1539-1546 ◽  
Author(s):  
Erik R. Swenson
Keyword(s):  
Pulmonary Edema ◽  
High Altitude ◽  
Time Course ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Alveolar Epithelium ◽  
Physical Exertion ◽  
Second Phase ◽  
Fluid Reabsorption ◽  
High Altitude Pulmonary Edema ◽  
Early Rise

Clinically evident high-altitude pulmonary edema (HAPE) is characterized by severe cyanosis, dyspnea, cough, and difficulty with physical exertion. This usually occurs within 1–2 days of ascent often with the additional stresses of any exercise and hypoventilation of sleep. The earliest events in evolving HAPE progress through clinically silent and then minimally recognized problems. The most important of these events involves an exaggerated elevation of pulmonary artery (PA) pressure in response to the ambient hypoxia. Hypoxic pulmonary vasoconstriction (HPV) is a rapid response with several phases. The first phase in both resistance arterioles and venules occurs within 5–10 min. This is followed by a second phase that further raises PA pressure by another 100% over the next 2–8 h. Combined with vasoconstriction and likely an unevenness in the regional strength of HPV, pressures in some microvascular regions with lesser arterial constriction rise to a level that initiates greater filtration of fluid into the interstitium. As pressures continue to rise local lymphatic clearance rates are exceeded and interstitial fluid begins to accumulate. Beyond elevation of transmural pressure gradients there is a dynamic noninjurious relaxation of microvascular and epithelial cell-cell contacts and an increase in transcellular vesicular transport which accelerate leakage. At some point with further pressure elevation, damage occurs with breaks of the barrier and bleeding into the alveolar space, a late-stage situation termed capillary stress failure. Earlier before there is fluid accumulation, alveolar hypoxia and hyperventilation-induced hypocapnia reduce the capacity of the alveolar epithelium to reabsorb sodium and water back into the interstitial space. More modest ascent which slows the rate of rise in PA pressure and allows for adaptive remodeling of the microvasculature, drugs which lower PA pressure, and those that can enhance fluid reabsorption will all forestall the deleterious early rise of microvascular pressures and diminished active alveolar fluid reabsorption that precede and underlie the development of HAPE.

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