Hypoxia and Inflammation: Insights From High-Altitude Physiology

Pham, Kathy; Parikh, Keval; Heinrich, Erica C.

doi:10.3389/fphys.2021.676782

Cited by 115 publications

(84 citation statements)

References 169 publications

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“…Hypoxia-induced inflammation impacts on the immune function and causes chronic disease and high-altitude illnesses [ 5 ]. In the same vein, redox homeostasis has been widely studied as disrupted by hypoxia conditioning [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

OxInflammation at High Altitudes: A Proof of Concept from the Himalayas

et al. 2022

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High-altitude locations are fascinating for investigating biological and physiological responses in humans. In this work, we studied the high-altitude response in the plasma and urine of six healthy adult trekkers, who participated in a trek in Nepal that covered 300 km in 19 days along a route in the Kanchenjunga Mountain and up to a maximum altitude of 5140 m. Post-trek results showed an unbalance in redox status, with an upregulation of ROS (+19%), NOx (+28%), neopterin (+50%), and pro-inflammatory prostanoids, such as PGE2 (+120%) and 15-deoxy-delta12,14-PGJ2 (+233%). The isoprostane 15-F2t-IsoP was associated with low levels of TAC (−18%), amino-thiols, omega-3 PUFAs, and anti-inflammatory CYP450 EPA-derived mediators, such as DiHETEs. The deterioration of antioxidant systems paves the way to the overload of redox and inflammative markers, as triggered by the combined physical and hypoxic stressors. Our data underline the link between oxidative stress and inflammation, which is related to the concept of OxInflammation into the altitude hypoxia fashion.

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Section: Introductionmentioning

confidence: 99%

OxInflammation at High Altitudes: A Proof of Concept from the Himalayas

et al. 2022

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“…This prompts the development of alternative interventions to prevent and/or reduce uncontrolled inflammatory response. Although low-intensity, short-term physical activity does not cause significant changes in immunological and physiological responses [9], studies dealing with the role of exercise [10][11][12][13] and relative hypoxic stress exposure [14] demonstrated that muscle-damaging exercise triggers a delayed systemic, predominantly anti-inflammatory, acute cytokine response.…”

Section: Introductionmentioning

confidence: 99%

Hypoxic and Hyperoxic Breathing as a Complement to Low-Intensity Physical Exercise Programs: A Proof-of-Principle Study

Balestra

Lambrechts

Mrakic‐Sposta

et al. 2021

IJMS

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Inflammation is an adaptive response to both external and internal stimuli including infection, trauma, surgery, ischemia-reperfusion, or malignancy. A number of studies indicate that physical activity is an effective means of reducing acute systemic and low-level inflammation occurring in different pathological conditions and in the recovery phase after disease. As a proof-of-principle, we hypothesized that low-intensity workout performed under modified oxygen supply would elicit a “metabolic exercise” inducing a hormetic response, increasing the metabolic load and oxidative stress with the same overall effect expected after a higher intensity or charge exercise. Herein, we report the effect of a 5-week low-intensity, non-training, exercise program in a group of young healthy subjects in combination with the exposure to hyperoxia (30% and 100% pO2, respectively) or light hypoxia (15% pO2) during workout sessions on several inflammation and oxidative stress parameters, namely hemoglobin (Hb), redox state, nitric oxide metabolite (NOx), inducible nitric oxide synthase (iNOS), inflammatory cytokine expression (TNF-α, interleukin (IL)-6, IL-10), and renal functional biomarkers (creatinine, neopterin, and urates). We confirmed our previous reports demonstrating that intermittent hyperoxia induces the normobaric oxygen paradox (NOP), a response overlapping the exposure to hypoxia. Our data also suggest that the administration of modified air composition is an expedient complement to a light physical exercise program to achieve a significant modulation of inflammatory and immune parameters, including cytokines expression, iNOS activity, and oxidative stress parameters. This strategy can be of pivotal interest in all those conditions characterized by the inability to achieve a sufficient workload intensity, such as severe cardiovascular alterations and articular injuries failing to effectively gain a significant improvement of physical capacity.

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“…When population reaches the plateau, the cardiomyocytes are subjected to prolonged hypoxic stimulation. Hypoxia will result in the disorder of energy metabolism in cardiomyocytes, accompanied by the accumulation of oxygen free radicals, thus destroying membranous permeability ( 7 ). On the other hand, ventricular hypertrophy is also a distinguishing feature of high-altitude heart disease ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Neutrophil to Lymphocyte Ratio and Myocardial Injury in Population Exposed to High Altitude

He¹,

He²,

Yang³

et al. 2021

Front. Cardiovasc. Med.

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Objective: Myocardial injury is a severe complication in population exposed to high altitude. As a new biomarker for inflammatory response, neutrophil to lymphocyte ratio (NLR) has been widely used to predict the prognosis of various diseases. In this study, we intend to explore the risk factors for myocardial injury at high altitude and examine the relationship between NLR level and development of myocardial injury.Methods: Consecutive patients admitted to a secondary general hospital at high altitude from June 2019 to May 2020 were selected into this retrospective study. Clinical and biochemical data were collected. According to the results of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzymes (CK-MB), and aspartate amino transferase (AST), patients were divided into myocardial injury group and normal group.Results: A total of 476 patients were enrolled in this study. Myocardial injury occurred in 158 patients (33.2%). We found that altitude, NLR, hemoglobin, total bilirubin, total cholesterol, and lipoprotein A in myocardial injury group were significantly higher than that in normal group (P < 0.05), while platelet count in myocardial injury group was significantly lower than that in normal group (P < 0.05). Logistic multivariate regression analysis revealed that there was an independent relationship between myocardial injury and smoke, NLR, hemoglobin (P < 0.05). By using Spearman correlation analysis, NLR was proved to have a significant positive correlation with LDH, CK, and CK-MB (P < 0.05) instead of AST. A receiver operating characteristic (ROC) curve was drawn to demonstrate that NLR could significantly predict the occurrence of myocardial injury with an area under the curve (AUC) of 0.594 (95% CI: 0.537–0.650, P < 0.05), and the level of 2.967 (sensitivity = 38.0%, specificity = 83.6%) was optimal cutoff value.Conclusion: The incidence of myocardial injury is high in population at high altitude. Smoke, hemoglobin, and NLR are independent factors related to myocardial injury. As a convenient and efficient marker, NLR is found to be closely associated with myocardial enzymes and have a predict role in the occurrence of myocardial injury. This study will provide a theoretical basis on NLR for the early diagnosis of myocardial injury at high altitude.

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Hypoxia and Inflammation: Insights From High-Altitude Physiology

Cited by 115 publications

References 169 publications

OxInflammation at High Altitudes: A Proof of Concept from the Himalayas

OxInflammation at High Altitudes: A Proof of Concept from the Himalayas

Hypoxic and Hyperoxic Breathing as a Complement to Low-Intensity Physical Exercise Programs: A Proof-of-Principle Study

Correlation Between Neutrophil to Lymphocyte Ratio and Myocardial Injury in Population Exposed to High Altitude

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