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      Orthostatic Resiliency During Successive Hypoxic, Hypoxic Orthostatic Challenge: Successful vs. Unsuccessful Cardiovascular and Oxygenation Strategies

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          Abstract

          Introduction: Rapid environmental changes, such as successive hypoxic-hypoxic orthostatic challenges (SHHOC) occur in the aerospace environment, and the ability to remain orthostatically resilient (OR) relies upon orchestration of physiological counter-responses. Counter-responses adjusting for hypoxia may conflict with orthostatic responses, and a misorchestration can lead to orthostatic intolerance (OI). The goal of this study was to pinpoint specific cardiovascular and oxygenation factors associated with OR during a simulated SHHOC.

          Methods: Thirty one men underwent a simulated SHHOC consisting of baseline (P0), normobaric hypoxia (Fi02 = 12%, P1), and max 60 s of hypoxic lower body negative pressure (LBNP, P2). Alongside anthropometric variables, non-invasive cardiovascular, central and peripheral tissue oxygenation parameters, were recorded. OI was defined as hemodynamic collapse during SHHOC. Comparison of anthropometric, cardiovascular, and oxygenation parameters between OR and OI was performed via Student’s t-test. Within groups, a repeated measures ANOVA test with Holm-Sidak post hoc test was performed. Performance diagnostics were performed to assess factors associated with OR/OI (sensitivity, specificity, positive predictive value PPV, and odd’s ratio OR).

          Results: Only 9/31 were OR, and 22/31 were OI. OR had significantly greater body mass index (BMI), weight, peripheral Sp02, longer R-R Interval (RRI) and lower heart rate (HR) at P0. During P1 OR exhibited significantly higher cardiac index (CI), stroke volume index (SVI), and lower systemic vascular resistance index (SVRI) than OI. Both groups exhibited a significant decrease in cerebral oxygenation (TOIc) with an increase in cerebral deoxygenated hemoglobin (dHbc), while the OI group showed a significant decrease in cerebral oxygenated hemoglobin (02Hbc) and peripheral oxygenation (TOIp) with an increase in peripheral deoxygenated hemoglobin (dHbp). During P2, OR maintained significantly greater CI, systolic, mean, and diastolic pressure (SAP, MAP, DAP), with a shortened RRI compared to the OI group, while central and peripheral oxygenation were not different. Body weight and BMI both showed high sensitivity (0.95), low specificity (0.33), a PPV of 0.78, with an OR of 0.92, and 0.61. P0 RRI showed a sensitivity of 0.95, specificity of 0.22, PPV 0.75, and OR of 0.99. Delta SVI had the highest performance diagnostics during P1 (sensitivity 0.91, specificity 0.44, PPV 0.79, and OR 0.8). Delta SAP had the highest overall performance diagnostics for P2 (sensitivity 0.95, specificity 0.67, PPV 0.87, and OR 0.9).

          Discussion: Maintaining OR during SHHOC is reliant upon greater BMI, body weight, longer RRI, and lower HR at baseline, while increasing CI and SVI, minimizing peripheral 02 utilization and decreasing SVRI during hypoxia. During hypoxic LBNP, the ability to remain OR is dependent upon maintaining SAP, via CI increases rather than SVRI. Cerebral oxygenation parameters, beyond 02Hbc during P1 did not differ between groups, suggesting that the during acute hypoxia, an increase in cerebral 02 consumption, coupled with increased peripheral 02 utilization does seem to play a role in OI risk during SHHOC. However, cardiovascular factors such as SVI are of more value in assessing OR/OI risk. The results can be used to implement effective aerospace crew physiological monitoring strategies.

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          Most cited references52

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          Hypoxemia, oxygen content, and the regulation of cerebral blood flow.

          This review highlights the influence of oxygen (O2) availability on cerebral blood flow (CBF). Evidence for reductions in O2 content (CaO2 ) rather than arterial O2 tension (PaO2 ) as the chief regulator of cerebral vasodilation, with deoxyhemoglobin as the primary O2 sensor and upstream response effector, is discussed. We review in vitro and in vivo data to summarize the molecular mechanisms underpinning CBF responses during changes in CaO2 . We surmise that 1) during hypoxemic hypoxia in healthy humans (e.g., conditions of acute and chronic exposure to normobaric and hypobaric hypoxia), elevations in CBF compensate for reductions in CaO2 and thus maintain cerebral O2 delivery; 2) evidence from studies implementing iso- and hypervolumic hemodilution, anemia, and polycythemia indicate that CaO2 has an independent influence on CBF; however, the increase in CBF does not fully compensate for the lower CaO2 during hemodilution, and delivery is reduced; and 3) the mechanisms underpinning CBF regulation during changes in O2 content are multifactorial, involving deoxyhemoglobin-mediated release of nitric oxide metabolites and ATP, deoxyhemoglobin nitrite reductase activity, and the downstream interplay of several vasoactive factors including adenosine and epoxyeicosatrienoic acids. The emerging picture supports the role of deoxyhemoglobin (associated with changes in CaO2 ) as the primary biological regulator of CBF. The mechanisms for vasodilation therefore appear more robust during hypoxemic hypoxia than during changes in CaO2 via hemodilution. Clinical implications (e.g., disorders associated with anemia and polycythemia) and future study directions are considered.
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            Does size matter? Clinical applications of scaling cardiac size and function for body size.

            Extensive evidence is available that cardiovascular structure and function, along with other biological properties that span the range of organism size and speciation, scale with body size. Although appreciation of such factors is commonplace in pediatrics, cardiovascular measurements in the adult population, with similarly wide variation in body size, are rarely corrected for body size. In this review, we describe the critical role of body size measurements in cardiovascular medicine. Using examples, we illustrate the confounding effects of body size. Current cardiovascular scaling practices are reviewed, as are limitations and alternative relationships between body and cardiovascular dimensions. The experimental evidence, theoretical basis, and clinical application of scaling of various functional parameters are presented. Appropriately scaled parameters aid diagnostic and therapeutic decision making in specific disease states such as hypertrophic cardiomyopathy and congestive heart failure. Large-scale studies in clinical populations are needed to define normative relationships for this purpose. Lack of appropriate consideration of body size in the evaluation of cardiovascular structure and function may adversely affect recognition and treatment of cardiovascular disease states in the adult patient.
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              Cerebral artery dilatation maintains cerebral oxygenation at extreme altitude and in acute hypoxia—an ultrasound and MRI study

              Transcranial Doppler is a widely used noninvasive technique for assessing cerebral artery blood flow. All previous high altitude studies assessing cerebral blood flow (CBF) in the field that have used Doppler to measure arterial blood velocity have assumed vessel diameter to not alter. Here, we report two studies that demonstrate this is not the case. First, we report the highest recorded study of CBF (7,950 m on Everest) and demonstrate that above 5,300 m, middle cerebral artery (MCA) diameter increases (n=24 at 5,300 m, 14 at 6,400 m, and 5 at 7,950 m). Mean MCA diameter at sea level was 5.30 mm, at 5,300 m was 5.23 mm, at 6,400 m was 6.66 mm, and at 7,950 m was 9.34 mm (P<0.001 for change between 5,300 and 7,950 m). The dilatation at 7,950 m reversed with oxygen. Second, we confirm this dilatation by demonstrating the same effect (and correlating it with ultrasound) during hypoxia (FiO2=12% for 3 hours) in a 3-T magnetic resonance imaging study at sea level (n=7). From these results, we conclude that it cannot be assumed that cerebral artery diameter is constant, especially during alterations of inspired oxygen partial pressure, and that transcranial 2D ultrasound is a technique that can be used at the bedside or in the remote setting to assess MCA caliber.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                27 October 2021
                2021
                : 12
                : 712422
                Affiliations
                [1] 1Department of Anaesthesiology and Intensive Care Medicine, Berlin Institute of Health, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin , Berlin, Germany
                [2] 2Center for Space Medicine and Extreme Environments Berlin, Berlin Institute of Health, Institute of Physiology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin , Berlin, Germany
                [3] 3Military University Hospital, Institute of Aviation Medicine , Prague, Czechia
                Author notes

                Edited by: Ronan Padraic Murphy, Dublin City University, Ireland

                Reviewed by: Martin Burtscher, University of Innsbruck, Austria; Richard D. Boyle, National Aeronautics and Space Administration (NASA), United States

                *Correspondence: Michael Nordine, michael.nordine@ 123456charite.de

                This article was submitted to Environmental, Aviation and Space Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2021.712422
                8578448
                2dc41a65-9af7-4f9a-ad7f-03beb80e39cf
                Copyright © 2021 Nordine, Treskatsch, Habazettl, Gunga, Brauns, Dosel, Petricek and Opatz.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 May 2021
                : 06 October 2021
                Page count
                Figures: 2, Tables: 5, Equations: 0, References: 52, Pages: 11, Words: 9674
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                lbnp,hypoxia,cardiovascular,oxygenation,aerospace
                Anatomy & Physiology
                lbnp, hypoxia, cardiovascular, oxygenation, aerospace

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