The air-blood barrier is well designed to accomplish the matching of gas diffusion with blood flow. This function is achieved by maintaining its thickness at ∼0.5 µm, a feature implying to keep extravascular lung water to the minimum. Exposure to hypobaric hypoxia, especially when associated with exercise, is a condition potentially leading to the development of the so-called high-altitude pulmonary edema (HAPE). This article presents a view of the physiopathology of HAPE by merging available data in humans exposed to high altitude with data from animal experimental approaches. A model is also presented to characterize HAPE nonsusceptible versus susceptible individuals based on the efficiency of alveolar-capillary oxygen uptake and estimated morphology of the air-blood barrier.
{"title":"Physiopathology of High-Altitude Pulmonary Edema.","authors":"Giuseppe Miserocchi","doi":"10.1089/ham.2024.0037","DOIUrl":"https://doi.org/10.1089/ham.2024.0037","url":null,"abstract":"<p><p>The air-blood barrier is well designed to accomplish the matching of gas diffusion with blood flow. This function is achieved by maintaining its thickness at ∼0.5 µm, a feature implying to keep extravascular lung water to the minimum. Exposure to hypobaric hypoxia, especially when associated with exercise, is a condition potentially leading to the development of the so-called high-altitude pulmonary edema (HAPE). This article presents a view of the physiopathology of HAPE by merging available data in humans exposed to high altitude with data from animal experimental approaches. A model is also presented to characterize HAPE nonsusceptible versus susceptible individuals based on the efficiency of alveolar-capillary oxygen uptake and estimated morphology of the air-blood barrier.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tom Citherlet, Antoine Raberin, Giorgio Manferdelli, Nicolas Bourdillon, Grégoire P Millet
Citherlet, Tom, Antoine Raberin, Giorgio Manferdelli, Nicolas Bourdillon, and Grégoire P Millet. Impact of the menstrual cycle (MC) on the cardiovascular and ventilatory responses during exercise in normoxia and hypoxia. High Alt Med Biol. 00:00-00, 2024. Introduction: Ovarian hormones influence several physiological functions in women. This study investigated how the hormonal variations across the menstrual cycle (MC) impact cardiovascular and ventilatory responses during rest and moderate exercise in normobaric hypoxia. Methods: Thirteen eumenorrheic women were tested during the early follicular (Fol1), late follicular (Fol2), and mid-luteal (Lut3) phases with measurement of hormonal levels. Heart rate (HR) variability, blood pressure, and baroreflex sensitivity (BRS) were evaluated at rest in normoxia. Ventilation (VE), peripheral oxygen saturation, and HR were monitored at rest and during moderate-intensity cycling exercise in hypoxia (FiO2 = 14%). Results: Despite expected hormone level variations, no significant changes were observed across the MC in HR variability (root mean square of successive differences; 64 (95% confidence interval [47, 81]) at Fol1, 54 [42, 66] at Fol2, 60 [44, 77] ms at Lut3), blood pressure (mean blood pressure; 85 [79, 90]), 87 [81, 93]), 84 [77, 92] mmHg), BRS (26 [17, 36], 28 [20, 35], 23 [17, 29] ms/mmHg), VE (rest: 8.9 [7.9, 9.8], 9.5 [9.0, 9.9], 9.0 [8.1, 9.9]; exercise: 53 [41, 66], 51.1 [36.4, 65.7], 54.4 [34.0, 74.8] l/min), peripheral oxygen saturation (rest: 89.8 [87.4, 92.1], 91.9 [88.7, 95.0], 90.2 [87.8, 92.6]; exercise: 80.5 [77.4, 83.5], 84.4 [80.4, 88.3], 81.9 [78.3, 85.4] %) HR (rest: 69.7 [60.2, 79.1], 70.8 [63.2, 78.3], 70.5 [64.0, 77.0]; exercise: 148 [136, 160], 146 [132, 161], 146 [132, 160] bpm), and cycling efficiency (0.17 [0.16, 0.18], 0.17 [0.13, 0.21], 0.16 [0.15, 0.18] %) (all p > 0.05). Discussion: From a practical point of view, there is no strong evidence of any usefulness of monitoring hormonal variations and the MC phases for women exercising in hypoxia.
汤姆-西瑟莱、安托万-拉贝兰、乔治-曼费德利、尼古拉斯-布尔迪隆和格雷瓜尔-P-米莱。月经周期(MC)对常氧和低氧运动时心血管和通气反应的影响。00:00-00, 2024.引言:卵巢激素影响女性的多种生理功能。本研究探讨了整个月经周期(MC)中的激素变化如何影响女性在常压低氧条件下进行静息和适度运动时的心血管和换气反应。研究方法在卵泡早期(Fol1)、卵泡晚期(Fol2)和黄体中期(Lut3)对 13 名月经过多的女性进行测试,测量她们的激素水平。在常氧静息状态下评估心率(HR)变异性、血压和气压反射敏感性(BRS)。在低氧状态下(FiO2 = 14%),监测静息时和中等强度骑车运动时的通气量(VE)、外周血氧饱和度和心率。结果:尽管预期激素水平会有变化,但在各 MC 中未观察到心率变异性的显著变化(连续差异的均方根;89.8[87.4,92.1],91.9[88.7,95.0],90.2[87.8,92.6];运动:80.5[77.4,83.5],84.4[80.4,88.3],81.9[78.3,85.4]%)心率(静息时:69.7[60.2,60.3];运动时:69.7[60.2,60.3]):69.7[60.2,79.1],70.8[63.2,78.3],70.5[64.0,77.0];运动:148[136,160],146[132,161],146[132,160] bpm)和骑行效率(0.17[0.16,0.18],0.17[0.13,0.21],0.16[0.15,0.18]%)(所有 p > 0.05)。讨论从实用角度来看,没有强有力的证据表明监测激素变化和 MC 阶段对在缺氧环境中锻炼的女性有任何帮助。
{"title":"Impact of the Menstrual Cycle on the Cardiovascular and Ventilatory Responses During Exercise in Normoxia and Hypoxia.","authors":"Tom Citherlet, Antoine Raberin, Giorgio Manferdelli, Nicolas Bourdillon, Grégoire P Millet","doi":"10.1089/ham.2024.0048","DOIUrl":"10.1089/ham.2024.0048","url":null,"abstract":"<p><p>Citherlet, Tom, Antoine Raberin, Giorgio Manferdelli, Nicolas Bourdillon, and Grégoire P Millet. Impact of the menstrual cycle (MC) on the cardiovascular and ventilatory responses during exercise in normoxia and hypoxia. <i>High Alt Med Biol.</i> 00:00-00, 2024. <b><i>Introduction:</i></b> Ovarian hormones influence several physiological functions in women. This study investigated how the hormonal variations across the menstrual cycle (MC) impact cardiovascular and ventilatory responses during rest and moderate exercise in normobaric hypoxia. <b><i>Methods:</i></b> Thirteen eumenorrheic women were tested during the early follicular (Fol1), late follicular (Fol2), and mid-luteal (Lut3) phases with measurement of hormonal levels. Heart rate (HR) variability, blood pressure, and baroreflex sensitivity (BRS) were evaluated at rest in normoxia. Ventilation (VE), peripheral oxygen saturation, and HR were monitored at rest and during moderate-intensity cycling exercise in hypoxia (F<sub>i</sub>O<sub>2</sub> = 14%). <b><i>Results:</i></b> Despite expected hormone level variations, no significant changes were observed across the MC in HR variability (root mean square of successive differences; 64 (95% confidence interval [47, 81]) at Fol1, 54 [42, 66] at Fol2, 60 [44, 77] ms at Lut3), blood pressure (mean blood pressure; 85 [79, 90]), 87 [81, 93]), 84 [77, 92] mmHg), BRS (26 [17, 36], 28 [20, 35], 23 [17, 29] ms/mmHg), VE (rest: 8.9 [7.9, 9.8], 9.5 [9.0, 9.9], 9.0 [8.1, 9.9]; exercise: 53 [41, 66], 51.1 [36.4, 65.7], 54.4 [34.0, 74.8] l/min), peripheral oxygen saturation (rest: 89.8 [87.4, 92.1], 91.9 [88.7, 95.0], 90.2 [87.8, 92.6]; exercise: 80.5 [77.4, 83.5], 84.4 [80.4, 88.3], 81.9 [78.3, 85.4] %) HR (rest: 69.7 [60.2, 79.1], 70.8 [63.2, 78.3], 70.5 [64.0, 77.0]; exercise: 148 [136, 160], 146 [132, 161], 146 [132, 160] bpm), and cycling efficiency (0.17 [0.16, 0.18], 0.17 [0.13, 0.21], 0.16 [0.15, 0.18] %) (all <i>p</i> > 0.05). <b><i>Discussion:</i></b> From a practical point of view, there is no strong evidence of any usefulness of monitoring hormonal variations and the MC phases for women exercising in hypoxia.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-04-29DOI: 10.1089/ham.2023.0081
Shiqiang Xiong, Jun Hou, Haixia Yang, Meiting Gong, Xin Ma, Xuhu Yang, Hongyang Zhang, Yao Ma, Liang Gao, Haifeng Pei
Xiong, Shiqiang, Jun Hou, Haixia Yang, Meiting Gong, Xin Ma, Xuhu Yang, Hongyang Zhang, Yao Ma, Liang Gao, and Haifeng Pei. The profiles of venous thromboembolism at different high altitudes High Alt Med Biol. 25:223-225, 2024.-This study investigated the incidence of venous thromboembolism (VTE) in high altitude (HA) and very HA areas. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) diagnosed between 2004 and 2022 in Yecheng, China, were retrospectively analyzed. The results showed that patients with PE at very HA had a higher risk of lower extremity DVT (OR 16.3 [95% CI 1.2-223.2], p = 0.036), than those at HA, especially in the early stages of very HA entry, and the harsh environment of very HA further exacerbated the risk of VTE. These findings emphasize the higher risk of PE development in very HA and the need for enhanced prevention and treatment in this area.
熊世强、侯军、杨海霞、龚梅婷、马昕、杨旭虎、张红阳、马瑶、高亮、裴海峰。00:000-000, 2024.本研究调查了高海拔地区和极高海拔地区静脉血栓栓塞症(VTE)的发病率。研究人员对中国叶城 2004 年至 2022 年期间确诊的深静脉血栓(DVT)或肺栓塞(PE)患者进行了回顾性分析。结果显示,在非常HA地区的PE患者发生下肢深静脉血栓的风险(OR 16.3 [95% CI 1.2-223.2],p = 0.036)高于在HA地区的患者,尤其是在进入非常HA地区的早期,非常HA地区的恶劣环境进一步加剧了VTE的风险。这些发现强调了在非常HA发生 PE 的风险较高,需要加强这方面的预防和治疗。
{"title":"The Profiles of Venous Thromboembolism at Different High Altitudes.","authors":"Shiqiang Xiong, Jun Hou, Haixia Yang, Meiting Gong, Xin Ma, Xuhu Yang, Hongyang Zhang, Yao Ma, Liang Gao, Haifeng Pei","doi":"10.1089/ham.2023.0081","DOIUrl":"10.1089/ham.2023.0081","url":null,"abstract":"<p><p>Xiong, Shiqiang, Jun Hou, Haixia Yang, Meiting Gong, Xin Ma, Xuhu Yang, Hongyang Zhang, Yao Ma, Liang Gao, and Haifeng Pei. The profiles of venous thromboembolism at different high altitudes <i>High Alt Med Biol.</i> 25:223-225, 2024.-This study investigated the incidence of venous thromboembolism (VTE) in high altitude (HA) and very HA areas. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) diagnosed between 2004 and 2022 in Yecheng, China, were retrospectively analyzed. The results showed that patients with PE at very HA had a higher risk of lower extremity DVT (OR 16.3 [95% CI 1.2-223.2], <i>p</i> = 0.036), than those at HA, especially in the early stages of very HA entry, and the harsh environment of very HA further exacerbated the risk of VTE. These findings emphasize the higher risk of PE development in very HA and the need for enhanced prevention and treatment in this area.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"223-225"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-13DOI: 10.1089/ham.2023.0106
Alexandre Fossati, Aleid C J Ruijs
Fossati, Alexandre, and Aleid C. J. Ruijs. Changes in fingertip cold-induced vasodilatation (hunting reaction) on acute exposure to altitude. High Alt Med Biol. 25:212-217, 2024. Objective: Cold-induced vasodilation (CIVD) of the extremities is an interesting part of human physiology. Although the physiology of the CIVD reaction remains unknown, there are indications that hypoxia influences our CIVD reaction. The objective of this study is to measure the influence of acute hypoxia on the CIVD reaction of the fingertips. Methods: The CIVD reaction was measured using immersion of one hand in a water bath of 0°C in 12 healthy volunteers at low (1,235 m) and high (3,800 m) altitude during 35 minutes. High altitude was reached by a 20-minute cable car ride. Testing was performed indoors (room temperature, 22-25°C) at both altitudes. Data analysis was performed measuring the parameters of the CIVD reaction. Differences were found using the paired Student's t-test. Results: There was no significant difference in baseline finger temperature, onset time, peak time, and frequency of the CIVD reaction. However, at high altitude, maximum temperature and amplitude were significantly higher, slope was steeper, and minimum temperature was lower. Conclusion: We did not find evidence for a diminished CIVD reaction at high altitude due to hypoxia.
{"title":"Changes in Fingertip Cold-Induced Vasodilatation (Hunting Reaction) on Acute Exposure to Altitude.","authors":"Alexandre Fossati, Aleid C J Ruijs","doi":"10.1089/ham.2023.0106","DOIUrl":"10.1089/ham.2023.0106","url":null,"abstract":"<p><p>Fossati, Alexandre, and Aleid C. J. Ruijs. Changes in fingertip cold-induced vasodilatation (hunting reaction) on acute exposure to altitude. <i>High Alt Med Biol</i>. 25:212-217, 2024. <b><i>Objective:</i></b> Cold-induced vasodilation (CIVD) of the extremities is an interesting part of human physiology. Although the physiology of the CIVD reaction remains unknown, there are indications that hypoxia influences our CIVD reaction. The objective of this study is to measure the influence of acute hypoxia on the CIVD reaction of the fingertips. <b><i>Methods:</i></b> The CIVD reaction was measured using immersion of one hand in a water bath of 0°C in 12 healthy volunteers at low (1,235 m) and high (3,800 m) altitude during 35 minutes. High altitude was reached by a 20-minute cable car ride. Testing was performed indoors (room temperature, 22-25°C) at both altitudes. Data analysis was performed measuring the parameters of the CIVD reaction. Differences were found using the paired Student's <i>t-test</i>. <b><i>Results:</i></b> There was no significant difference in baseline finger temperature, onset time, peak time, and frequency of the CIVD reaction. However, at high altitude, maximum temperature and amplitude were significantly higher, slope was steeper, and minimum temperature was lower. <b><i>Conclusion:</i></b> We did not find evidence for a diminished CIVD reaction at high altitude due to hypoxia.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"212-217"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-17DOI: 10.1089/ham.2023.0117
Fei Han, Tao Luo, Xudong Wen, Wei Jiang, Yan Wu, Yubo Li, Pan Long
{"title":"<i>Letter to the Editor:</i> When Mountain Sickness Meets COVID-19 Infection: A Rare Ocular Cotton-Wool Spot Presentation.","authors":"Fei Han, Tao Luo, Xudong Wen, Wei Jiang, Yan Wu, Yubo Li, Pan Long","doi":"10.1089/ham.2023.0117","DOIUrl":"10.1089/ham.2023.0117","url":null,"abstract":"","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"251-253"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-04-29DOI: 10.1089/ham.2024.0024
Andrew M Luks, Colin K Grissom
Luks AM, Grissom CK. Evaluation and Management of the Individual with Recurrent HAPE. High Alt Med Biol. 25:238-246, 2024. Individuals with a history of acute altitude illness often seek recommendations from medical providers on how to prevent such problems on future ascents to high elevation. Although many of these cases can be managed with pharmacologic prophylaxis and counseling about the appropriate rate of ascent alone, there are some situations in which further diagnostic evaluation may also be warranted. One such situation is the individual with recurrent episodes of high altitude pulmonary edema (HAPE), as one of several predisposing factors may be present that warrants additional interventions beyond pharmacologic prophylaxis and slow ascent and may even preclude future travel to high altitude. This review considers this situation in greater detail. Structured around the case of an otherwise healthy 27-year-old individual with recurrent episodes of HAPE who would like to climb Denali (6,190 m), the review examines the known risk factors for disease and then provides guidance regarding when and how to evaluate such individuals and appropriate steps to prevent HAPE on further ascents to high elevation. Except in rare circumstances, a history of recurrent HAPE does not preclude further ascent to high elevation, as a multipronged approach including pharmacologic prophylaxis, careful planning about the rate of ascent, and the degree of physical effort and other strategies, such as preacclimatization, staged ascent, and use of hypoxic tents, can be employed to reduce the risk of recurrence with future travel.
{"title":"Evaluation and Management of the Individual with Recurrent High Altitude Pulmonary Edema.","authors":"Andrew M Luks, Colin K Grissom","doi":"10.1089/ham.2024.0024","DOIUrl":"10.1089/ham.2024.0024","url":null,"abstract":"<p><p>Luks AM, Grissom CK. Evaluation and Management of the Individual with Recurrent HAPE. <i>High Alt Med Biol.</i> 25:238-246, 2024. Individuals with a history of acute altitude illness often seek recommendations from medical providers on how to prevent such problems on future ascents to high elevation. Although many of these cases can be managed with pharmacologic prophylaxis and counseling about the appropriate rate of ascent alone, there are some situations in which further diagnostic evaluation may also be warranted. One such situation is the individual with recurrent episodes of high altitude pulmonary edema (HAPE), as one of several predisposing factors may be present that warrants additional interventions beyond pharmacologic prophylaxis and slow ascent and may even preclude future travel to high altitude. This review considers this situation in greater detail. Structured around the case of an otherwise healthy 27-year-old individual with recurrent episodes of HAPE who would like to climb Denali (6,190 m), the review examines the known risk factors for disease and then provides guidance regarding when and how to evaluate such individuals and appropriate steps to prevent HAPE on further ascents to high elevation. Except in rare circumstances, a history of recurrent HAPE does not preclude further ascent to high elevation, as a multipronged approach including pharmacologic prophylaxis, careful planning about the rate of ascent, and the degree of physical effort and other strategies, such as preacclimatization, staged ascent, and use of hypoxic tents, can be employed to reduce the risk of recurrence with future travel.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"238-246"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. High Alt Med Biol. 25:174-185, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system in vivo remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O2 affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO2%) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO2% difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In ex vivo experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94β-His146β in nitrosyl -Hb(NO-Hb), NO-HbβCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.
周晓颖、苏文婷、鲍全伟、崔宇、李晓旭、杨一东、杨承忠、王成元、焦莉、陈德伟和黄健。一氧化氮通过调节血红蛋白的氧运输改善小鼠缺氧的影响缺氧是缺血、癌症和剧烈运动中常见的病理和生理现象。一氧化氮(NO)在缺氧性血管扩张中充当内皮源性松弛因子,并充当血红蛋白(Hb)的异位调节因子。然而,NO 对体内血液系统的最终影响仍然未知,尤其是在极端缺氧的环境中。NO 对 Hb 结构的调节是否能改善氧的运输仍不清楚。因此,我们研究了 NO 是否会改变 Hb 的氧亲和力(Hb-O2 亲和力)以保护极度缺氧的小鼠。将小鼠暴露于不同浓度的 NO 的严重缺氧环境中,记录小鼠的存活时间、运动能力和其他身体指标。与 0 ppm 组(4.98 ± 1.23 分钟)相比,5 ppm NO 组(6.09 ± 1.29 分钟)和 10 ppm NO 组(6.39 ± 1.58 分钟)的存活时间延长。当小鼠吸入 20 ppm NO 时,脑缺氧得到缓解,运动耗竭时间延长(24.70 ± 6.87 分钟 vs. 20.23 ± 6.51 分钟)。此外,动脉血氧饱和度(SO2%)差异(49.64 ± 7.29% vs. 42.90 ± 4.30%)和动静脉 SO2% 差异(25.14 ± 8.95% vs. 18.10 ± 6.90%)明显增加。在体内外实验中,氧平衡曲线(OEC)左移,P50 从 43.77 ± 2.49 mmHg(0 ppm NO)下降到 40.97 ± 1.40 mmHg(100 ppm NO)和 38.36 ± 2.78 mmHg(200 ppm NO)。此外,引入 200 ppm NO 后,Hb 的玻尔效应增强(-0.72 ± 0.062 vs. -0.65 ± 0.051),这可能使 Hb 更容易在较低 pH 值下卸载组织中的氧气。晶体结构显示,在亚硝基-Hb(NO-Hb)、NO-HbβCSO93 和 S-亚硝基Hb(SNO-Hb)中,Asp94β-His146β 之间的距离比正常 Hb(T-Hb,分别为 3.7 Å、4.3 Å 和 5.8 Å,而 T-Hb 为 3.5 Å)要大。此外,氢键不太可能形成,这是弛缓 Hb(R-Hb)的一个关键局限。NO 与 Hb 相互作用时,氢键和盐桥的形成较少,从而促进了弛豫。我们推测,NO 通过促进红细胞在肺中的氧负荷和组织中的氧卸载,改善了小鼠缺氧的影响。
{"title":"Nitric Oxide Ameliorates the Effects of Hypoxia in Mice by Regulating Oxygen Transport by Hemoglobin.","authors":"Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, Jian Huang","doi":"10.1089/ham.2023.0044","DOIUrl":"10.1089/ham.2023.0044","url":null,"abstract":"<p><p>Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. <i>High Alt Med Biol</i>. 25:174-185, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system <i>in vivo</i> remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O<sub>2</sub> affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO<sub>2</sub>%) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO<sub>2</sub>% difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In <i>ex vivo</i> experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94β-His146β in nitrosyl -Hb(NO-Hb), NO-HbβCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"174-185"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Pulmonary hypertension (PH) is a prevalent adverse cardiovascular event at high-altitude environments. Prolonged exposure to high altitudes may result in myocardial injury, which is associated with poor clinical outcomes. This study aims to investigate the clinical characteristics of myocardial injury in patients with PH at high altitude. Methods: Consecutive patients admitted to a general tertiary hospital at the altitude of 3,650 m were selected into this retrospective study. Clinical and biochemical data were collected, as well as based on cardiac troponin I (cTnI) and echocardiography, patients were divided into myocardial injury group and non-myocardial injury group. Results: A total of 231 patients were enrolled, among whom 29 (12.6%) had myocardial injury. We found that body mass index, left ventricular end-diastolic dimension, and serum level of creatine kinase-MB (CK-MB) in myocardial injury group were significantly higher than non-myocardial injury group. Spearman correlation analysis revealed that cTnI has a significant positive correlation with CK-MB and lactic dehydrogenase instead of aspartate aminotransferase. A receiver operating characteristic curve was drawn to demonstrate that CK-MB could significantly predict the occurrence of myocardial injury with an area under the curve of 0.749, and a level of 3.035 (sensitivity = 59.3%, specificity = 90.5%) was optimal cutoff value. Conclusion: The incidence of myocardial injury in highlanders with PH is significant. CK-MB, as a convenient and efficient marker, has been found to be closely associated with cTnI and plays a predictive role in the occurrence of myocardial injury with PH in individuals exposed to high altitude.
{"title":"Clinical Analysis of Myocardial Injury in Highlanders with Pulmonary Hypertension.","authors":"Maolin Zhao, Qianjin Wu, Wangsheng Duanmu, Junxian Shen, Weixin Yuan, Yingbin Sun, Xu Zhang, Jinbao Zhang, Siyi He","doi":"10.1089/ham.2023.0075","DOIUrl":"10.1089/ham.2023.0075","url":null,"abstract":"<p><p><b><i>Background:</i></b> Pulmonary hypertension (PH) is a prevalent adverse cardiovascular event at high-altitude environments. Prolonged exposure to high altitudes may result in myocardial injury, which is associated with poor clinical outcomes. This study aims to investigate the clinical characteristics of myocardial injury in patients with PH at high altitude. <b><i>Methods:</i></b> Consecutive patients admitted to a general tertiary hospital at the altitude of 3,650 m were selected into this retrospective study. Clinical and biochemical data were collected, as well as based on cardiac troponin I (cTnI) and echocardiography, patients were divided into myocardial injury group and non-myocardial injury group. <b><i>Results:</i></b> A total of 231 patients were enrolled, among whom 29 (12.6%) had myocardial injury. We found that body mass index, left ventricular end-diastolic dimension, and serum level of creatine kinase-MB (CK-MB) in myocardial injury group were significantly higher than non-myocardial injury group. Spearman correlation analysis revealed that cTnI has a significant positive correlation with CK-MB and lactic dehydrogenase instead of aspartate aminotransferase. A receiver operating characteristic curve was drawn to demonstrate that CK-MB could significantly predict the occurrence of myocardial injury with an area under the curve of 0.749, and a level of 3.035 (sensitivity = 59.3%, specificity = 90.5%) was optimal cutoff value. <b><i>Conclusion:</i></b> The incidence of myocardial injury in highlanders with PH is significant. CK-MB, as a convenient and efficient marker, has been found to be closely associated with cTnI and plays a predictive role in the occurrence of myocardial injury with PH in individuals exposed to high altitude.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"205-211"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-04-29DOI: 10.1089/ham.2023.0065
Eric Hermand, Léo Lesaint, Laura Denis, Jean-Paul Richalet, François J Lhuissier
Hermand, Eric, Léo Lesaint, Laura Denis, Jean-Paul Richalet, and François J. Lhuissier. A step test to evaluate the susceptibility to severe high-altitude illness in field conditions. High Alt Med Biol. 25:158-163, 2024.-A laboratory-based hypoxic exercise test, performed on a cycle ergometer, can be used to predict susceptibility to severe high-altitude illness (SHAI) through the calculation of a clinicophysiological SHAI score. Our objective was to design a field-condition test and compare its derived SHAI score and various physiological parameters, such as peripheral oxygen saturation (SpO2), and cardiac and ventilatory responses to hypoxia during exercise (HCRe and HVRe, respectively), to the laboratory test. A group of 43 healthy subjects (15 females and 28 males), with no prior experience at high altitude, performed a hypoxic cycle ergometer test (simulated altitude of 4,800 m) and step tests (20 cm high step) at 3,000, 4,000, and 4,800 m simulated altitudes. According to tested altitudes, differences were observed in O2 desaturation, heart rate, and minute ventilation (p < 0.001), whereas the computed HCRe and HVRe were not different (p = 0.075 and p = 0.203, respectively). From the linear relationships between the step test and SHAI scores, we defined a risk zone, allowing us to evaluate the risk of developing SHAI and take adequate preventive measures in field conditions, from the calculated step test score for the given altitude. The predictive value of this new field test remains to be validated in real high-altitude conditions.
{"title":"A Step Test to Evaluate the Susceptibility to Severe High-Altitude Illness in Field Conditions.","authors":"Eric Hermand, Léo Lesaint, Laura Denis, Jean-Paul Richalet, François J Lhuissier","doi":"10.1089/ham.2023.0065","DOIUrl":"10.1089/ham.2023.0065","url":null,"abstract":"<p><p>Hermand, Eric, Léo Lesaint, Laura Denis, Jean-Paul Richalet, and François J. Lhuissier. A step test to evaluate the susceptibility to severe high-altitude illness in field conditions. <i>High Alt Med Biol.</i> 25:158-163, 2024.-A laboratory-based hypoxic exercise test, performed on a cycle ergometer, can be used to predict susceptibility to severe high-altitude illness (SHAI) through the calculation of a clinicophysiological SHAI score. Our objective was to design a field-condition test and compare its derived SHAI score and various physiological parameters, such as peripheral oxygen saturation (SpO<sub>2</sub>), and cardiac and ventilatory responses to hypoxia during exercise (HCRe and HVRe, respectively), to the laboratory test. A group of 43 healthy subjects (15 females and 28 males), with no prior experience at high altitude, performed a hypoxic cycle ergometer test (simulated altitude of 4,800 m) and step tests (20 cm high step) at 3,000, 4,000, and 4,800 m simulated altitudes. According to tested altitudes, differences were observed in O<sub>2</sub> desaturation, heart rate, and minute ventilation (<i>p</i> < 0.001), whereas the computed HCRe and HVRe were not different (<i>p</i> = 0.075 and <i>p</i> = 0.203, respectively). From the linear relationships between the step test and SHAI scores, we defined a risk zone, allowing us to evaluate the risk of developing SHAI and take adequate preventive measures in field conditions, from the calculated step test score for the given altitude. The predictive value of this new field test remains to be validated in real high-altitude conditions.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"158-163"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2021-07-01DOI: 10.1089/ham.2021.0020
Benoit Champigneulle, Ivan Hancco, Richard Renan, Stéphane Doutreleau, Emeric Stauffer, Aurélien Pichon, Julien V Brugniaux, Hélène Péré, Pierre Bouzat, David Veyer, Samuel Verges
Champigneulle, Benoit, Ivan Hancco, Richard Renan, Stéphane Doutreleau, Emeric Stauffer, Aurélien Pichon, Julien V. Brugniaux, Hélène Péré, Pierre Bouzat, David Veyer, and Samuel Verges. High-altitude environment and COVID-19: SARS-CoV-2 seropositivity in the highest city in the world. High Alt Med Biol. 22: 000-000, 2021. Background: A reduced coronavirus disease 2019 (COVID-19) diffusion has been suggested in high-altitude areas but remained questionable. Aims of this study were to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity as well as the risk factors associated in La Rinconada, the highest city in the world (5,100-5,300 m), a gold-mining town located in southeastern Peru where >50,000 dwellers live in precarious sanitary conditions. Materials and Methods: We performed a cross-sectional study during a 1-week period in October 2020, using point-of-care lateral flow serological assays allowing detection of antibodies directed against SARS-CoV-2 among voluntary dwellers in La Rinconada. Participants were also questioned about potential occupational and environmental risk factors of COVID-19 occurrence. Results: In a sample of 159 dwellers tested in La Rinconada, 48.4% [95% confidence interval, CI: 40.5-56.4] were seropositive for the SARS-CoV-2. Occurrence of at least one symptom compatible with the COVID-19 over the past 6 months remained the only significant factor associated with SARS-CoV-2 seropositivity (adjusted odds ratio: 3.27; [95% CI: 1.70-6.44]; p < 0.001). Conclusions: The high rate of SARS-CoV-2 seropositivity observed in this small sample of highlanders does not support a protective effect of high-altitude against the COVID-19 spread and demonstrates its large dissemination in vulnerable populations. Clinical Trial Registration number: NCT04604249.
Champigneulle, Benoit, Ivan Hancco, Richard Renan, Stéphane Doutreleau, Emeric Stauffer, Aurélien Pichon, Julien V. Brugniaux, Hélène Péré, Pierre Bouzat, David Veyer, and Samuel Verges.高海拔环境与 COVID-19:世界海拔最高城市的 SARS-CoV-2 血清阳性反应。22: 000-000, 2021.背景:有人认为冠状病毒疾病2019(COVID-19)在高海拔地区的扩散会减弱,但仍有疑问。本研究的目的是估计拉林科纳达(La Rinconada)的严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)血清阳性率以及相关风险因素。拉林科纳达是世界上海拔最高的城市(海拔 5100-5300 米),位于秘鲁东南部,是一个金矿小镇,超过 50,000 名居民生活在不稳定的卫生条件下。材料与方法我们在 2020 年 10 月进行了一项为期一周的横断面研究,采用的是护理点侧流血清学检测法,可以在拉林科纳达的自愿居民中检测出针对 SARS-CoV-2 的抗体。此外,还询问了参与者有关 COVID-19 发生的潜在职业和环境风险因素。结果在拉林科纳达接受检测的 159 名居民中,48.4%[95% 置信区间:40.5-56.4] 对 SARS-CoV-2 呈血清阳性。在过去 6 个月中至少出现过一种与 COVID-19 相符的症状仍然是与 SARS-CoV-2 血清阳性相关的唯一重要因素(调整后的几率比:3.27;[95% 置信区间:1.70-6.44];P 结论:SARS-CoV-2 血清阳性率较高的原因是在过去 6 个月中至少出现过一种与 COVID-19 相符的症状:在这一高原小样本中观察到的高SARS-CoV-2血清阳性率不支持高海拔对COVID-19传播的保护作用,并证明了它在易感人群中的广泛传播。临床试验注册号:NCT04604249:NCT04604249。
{"title":"High-Altitude Environment and COVID-19: SARS-CoV-2 Seropositivity in the Highest City in the World.","authors":"Benoit Champigneulle, Ivan Hancco, Richard Renan, Stéphane Doutreleau, Emeric Stauffer, Aurélien Pichon, Julien V Brugniaux, Hélène Péré, Pierre Bouzat, David Veyer, Samuel Verges","doi":"10.1089/ham.2021.0020","DOIUrl":"10.1089/ham.2021.0020","url":null,"abstract":"<p><p>Champigneulle, Benoit, Ivan Hancco, Richard Renan, Stéphane Doutreleau, Emeric Stauffer, Aurélien Pichon, Julien V. Brugniaux, Hélène Péré, Pierre Bouzat, David Veyer, and Samuel Verges. High-altitude environment and COVID-19: SARS-CoV-2 seropositivity in the highest city in the world. <i>High Alt Med Biol.</i> 22: 000-000, 2021. <b><i>Background:</i></b> A reduced coronavirus disease 2019 (COVID-19) diffusion has been suggested in high-altitude areas but remained questionable. Aims of this study were to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity as well as the risk factors associated in La Rinconada, the highest city in the world (5,100-5,300 m), a gold-mining town located in southeastern Peru where >50,000 dwellers live in precarious sanitary conditions. <b><i>Materials and Methods:</i></b> We performed a cross-sectional study during a 1-week period in October 2020, using point-of-care lateral flow serological assays allowing detection of antibodies directed against SARS-CoV-2 among voluntary dwellers in La Rinconada. Participants were also questioned about potential occupational and environmental risk factors of COVID-19 occurrence. <b><i>Results:</i></b> In a sample of 159 dwellers tested in La Rinconada, 48.4% [95% confidence interval, CI: 40.5-56.4] were seropositive for the SARS-CoV-2. Occurrence of at least one symptom compatible with the COVID-19 over the past 6 months remained the only significant factor associated with SARS-CoV-2 seropositivity (adjusted odds ratio: 3.27; [95% CI: 1.70-6.44]; <i>p</i> < 0.001). <b><i>Conclusions:</i></b> The high rate of SARS-CoV-2 seropositivity observed in this small sample of highlanders does not support a protective effect of high-altitude against the COVID-19 spread and demonstrates its large dissemination in vulnerable populations. Clinical Trial Registration number: NCT04604249.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"218-222"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39060277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}