Hemoglobin Changes After Long-Term Intermittent Work at High Altitude

Akunov, Almaz; Sydykov, Akylbek; Toktash, Turgun; Doolotova, Anara; Sarybaev, Akpay

doi:10.3389/fphys.2018.01552

Cited by 30 publications

(23 citation statements)

References 49 publications

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“…Because NO is mainly degraded by the blood, we expected that changing hematologic properties such as free hemoglobin (Hgb) or hematocrit (Hct) would alter NO-mediated signaling. Hematocrit varies with sex [165], and can be elevated by drugs [89,166] or prolonged exposure to high altitude [167,168]. While NO is typically degraded by hemoglobin (Hgb) in RBCs, free Hgb in the plasma can scavenge NO up to 1,000-fold faster than within RBCs [125,143].…”

Section: Influence Of Plasma Free Hemoglobin and Hematocrit On Vasodymentioning

confidence: 99%

Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics

2020

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Nitric oxide (NO) is a gaseous signaling molecule that plays an important role in neurovascular coupling. NO produced by neurons diffuses into the smooth muscle surrounding cerebral arterioles, driving vasodilation. However, the rate of NO degradation in hemoglobin is orders of magnitude higher than in brain tissue, though how this might impact NO signaling dynamics is not completely understood. We used simulations to investigate how the spatial and temporal patterns of NO generation and degradation impacted dilation of a penetrating arteriole in cortex. We found that the spatial location of NO production and the size of the vessel both played an important role in determining its responsiveness to NO. The much higher rate of NO degradation and scavenging of NO in the blood relative to the tissue drove emergent vascular dynamics. Large vasodilation events could be followed by post-stimulus constrictions driven by the increased degradation of NO by the blood, and vasomotion-like 0.1-0.3 Hz oscillations could also be generated. We found that these dynamics could be enhanced by elevation of free hemoglobin in the plasma, which occurs in diseases such as malaria and sickle cell anemia, or following blood transfusions. Finally, we show that changes in blood flow during hypoxia or hyperoxia could be explained by altered NO degradation in the parenchyma. Our simulations suggest that many common vascular dynamics may be emergent phenomena generated by NO degradation by the blood or parenchyma.

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Section: Influence Of Plasma Free Hemoglobin and Hematocrit On Vasodymentioning

confidence: 99%

Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics

2020

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“…Because NO is mainly degraded by the blood, we expected that changing hematologic properties such as free hemoglobin (Hgb) or hematocrit (Hct) would alter NO-mediated signaling. Hematocrit varies with sex 140 , and can be elevated by drugs 84, 141 or prolonged exposure to high altitude 142, 143 . While NO is typically degraded by hemoglobin (Hgb) in RBCs, free Hgb in the plasma can scavenge NO up to 1,000-fold faster than in the RBC membrane 144, 145 .…”

Section: Resultsmentioning

confidence: 99%

Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics

Haselden

Kedarasetti

Drew

2019

Preprint

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Nitric oxide (NO) is a gaseous signaling molecule that plays an important role 1 in neurovascular coupling. NO produced by neurons diffuses into the smooth muscle 2 surrounding cerebral arterioles, driving vasodilation.However, the rate of NO 3 degradation in hemoglobin is orders of magnitude higher than in brain tissue, though how 4 this might impact NO signaling dynamics is not completely understood. We used 5 simulations to investigate how the spatial and temporal patterns of NO generation and 6 degradation impacted dilation of a penetrating arteriole in cortex. We found that the 7 spatial location of NO production and the size of the vessel both played an important role 8 in determining its responsiveness to NO. The much higher rate of NO degradation and 9 scavenging of NO in the blood relative to the tissue drove emergent vascular dynamics. 10Large vasodilation events could be followed by post-stimulus constrictions driven by the 11 increased degradation of NO by the blood, and vasomotion-like 0.1-0.3 Hz oscillations 12 could also be generated. We found that these dynamics could be enhanced by elevation 13 of free hemoglobin in the plasma, which occurs in diseases such as malaria and sickle 14 cell anemia, or following blood transfusions. Finally, we show that changes in blood flow 15 during hypoxia or hyperoxia could be explained by altered NO degradation in the 16 parenchyma. Our simulations suggest that many common vascular dynamics may be 17 emergent phenomenon generated by NO degradation by the blood or parenchyma. 18 19 20 21 22 23 fold faster than the surrounding tissue 73,75-78 . Because NO reacts with hemoglobin at 70 much higher rates than the tissue, the hemoglobin present inside a vessel plays an 71 appreciable role in shaping NO concentrations at the smooth muscle where it acts. Under 72 normal conditions, most hemoglobin in the blood in confined to red blood cells, with low 73 levels in the plasma. Due to fluid dynamics 79-81 , red blood cells will be excluded from the 74 few micrometer-thick cell free layer next to the endothelial cells, providing a measure of 75 spatial separation between the region of high NO degradation and the smooth muscles. 76However, if hemoglobin levels in the plasma rise (due to pathology or other processes) 82-77 89 , this will greatly increase the degradation rate of NO in the plasma, leading to decreased 78 NO levels in the smooth muscle 83,[90][91][92] . NO's diffusive properties and known reaction 79 rates lend themselves to computational approaches to understanding NO 80 signaling 38,59,75,78,[93][94][95][96][97][98] . While there have been detailed and informative models of NO 81 signaling from endothelial cells 59,91,96,99,100 showing that the size of the arteriole 75 and 82properties of the blood 96 are vital components to understanding NO signaling, the insight 83 from these models that the spatial location of blood plays an important role in the 84 degradation of NO has not been applied to neurovascular coupling or in a dynamic setting. 85 Intriguingly, in...

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“…This type of hypoxic exposure is hereafter termed as 'irregular short-term intermittent hypoxia'. Additionally, four prospective, [32][33][34][35] four cross-sectional, [36][37][38][39] two longitudinal 40 41 and four observational studies [42][43][44][45] were included (table 2). Eleven of these studies investigated repeated exposure of 4-14 days to hypoxia, 32 36-45 while two studies investigated repeated hypoxic exposure lasting 3-4 weeks.…”

Section: General Overviewmentioning

confidence: 99%

Does intermittent exposure to high altitude increase the risk of cardiovascular disease in workers? A systematic narrative review

et al. 2020

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ObjectiveSeveral working groups (eg, miners, flight crews and soldiers) are subjected to chronic intermittent hypoxic exposure. The cardiovascular implications have been studied but not systematically reviewed with focus on possible negative health implications. The aim of the present review was to systematically evaluate the hypothesis that intermittent hypoxic exposure causes cardiovascular stress detrimental to health in workers.DesignSystematic review.Data sourcesElectronic database search of PubMed, Scopus and Web of Science up to April 2020.Eligibility criteriaStudies of workers ≥18 years repeatedly subjected to months to years of irregular intermittent hypoxia, lasting from a few hours (eg, flight crews), one or a few days (eg, soldiers), or several days to weeks (eg, miners working at high altitude), written in English and evaluating the effect of intermittent hypoxia on cardiovascular disease were included. Animal studies, books, book chapters, personal communication and abstracts were excluded. The primary outcome measure was changes in standardised mortality ratio.Data extraction and synthesisTwo independent reviewers extracted data and assessed risk of bias using the Cochrane Collaboration’s tool.Results119 articles were identified initially, 31 of which met the inclusion criteria. Of these, 17 were retrospective cohort mortality studies (irregular short-term intermittent hypoxia), and 14 studies were observational (long-term intermittent hypoxia). The population of irregular short-term intermittent hypoxia users (flight crew) showed a lower mortality by cardiovascular disease. Long-term intermittent hypoxia over several years such as in miners or soldiers may produce increased levels of cardiac disorders (12 studies), though this is probably confounded by factors such as obesity and socioeconomic status.ConclusionThis systematic narrative review found that cardiovascular disease mortality in flight crews is lower than average, whereas miners and soldiers exposed to intermittent hypoxia experience increased risks of cardiovascular diseases. The impact of socioeconomic status and lifestyle appears of importance.PROSPERO registry numberCRD42020171301.

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Hemoglobin Changes After Long-Term Intermittent Work at High Altitude

Cited by 30 publications

References 49 publications

Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics

Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics

Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics

Does intermittent exposure to high altitude increase the risk of cardiovascular disease in workers? A systematic narrative review

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