Empirically-derived relationship between haemoglobin concentration (Hb) and arterial partial pressure of oxygen (Pa in Andean men

From (used with permission). The average Hb of young high-altitude natives is represented by an empirical equation that expresses Hb as a function of Pa This equation was derived using data collated from several studies, which investigated approximately 200 healthy men aged 18–45 years. Measurements were largely made in members of the native Quechua population at altitudes ranging from sea level to 4860 m, and Pa was calculated from arterial haemoglobin oxygen saturation. Pa is primarily determined by the altitude of residence, and for a given altitude, a Hb of more than two standard deviations above average is considered excessive ().<p><b>Copyright information:</b></p><p>Taken from "The human side of hypoxia-inducible factor"</p><p></p><p>British Journal of Haematology 2008;141(3):325-334.</p><p>Published online Jan 2008</p><p>PMCID:PMC2408651.</p><p>© 2008 The Authors Journal compilation © 2008 Blackwell Publishing Ltd</p

Sensitivity of VHL-1–Regulated Genes to Defects in Extracellular Matrix-Associated Proteins

<div><p>RNase protection assays showing altered expression of VHL-1–regulated genes that are HIF-1 independent (upper six panels) and HIF-1 dependent (F22B5.4) in worms bearing mutations affecting (A) procollagen prolyl and lysyl hydroxylases and (B) other extracellular matrix-associated proteins. A common pattern of upregulation is observed in <i>hif-1; vhl-1, vhl-1, dpy-18, let-268, gon-1, mig-17,</i> and <i>unc-6</i> worms but not other mutants. This contrasts with the HIF-1–dependent gene F22B5.4, which is upregulated in <i>vhl-1</i> worms but none of the other mutants.</p> <p>(C) RNase protection assay for C01B4.9 illustrating DPY-18–mediated changes in expression that are independent of HIF-1.</p></div

Responses of VHL-1–Dependent, HIF-1–Independent Genes to <i>egl-9</i> Inactivation, Hypoxia, and 2-Oxoglutarate Dioxygenase Inhibitors

<p>RNase protection assays showing regulation of VHL-1–dependent, HIF-1–independent genes by (A) EGL-9 and hypoxia and (B) pharmacological inhibitors of 2-oxoglutarate dioxygenases: DIP and DMOG. None of the genes is regulated by EGL-9, but two genes (C01B4.7 and C01B4.8) show modest induction by hypoxia, DIP, and DMOG.</p

Sensitivities to Hypoxia for Individual Participants

<p>Results are shown in terms of the number of (normal control group) standard deviations by which each participant's response differed from the mean response of the normal control participants. The patients with CP were significantly different from the normal control group in their ventilatory and pulmonary vascular responses to both mild and moderate hypoxia, and in their heart rate responses to mild hypoxia. BP, blood pressure.</p

Systemic Vascular Responses to Mild and Moderate Hypoxia

<div><p>(A and B) Heart rate. Mild hypoxia provoked a rise of 11.7 beats/min in the CP patient group, compared with 3.6 beats/min in normal control participants ( <i>p</i> < 0.05). No other statistically significant differences in systemic vascular responses were detected between these two groups. </p> <p>(C and D) Blood pressure, showing systolic pressure (upper plot) and diastolic pressure (lower plot).</p> <p>(E and F) Cardiac output, assessed non-invasively using Doppler echocardiography.</p> <p>All responses are shown during mild (A, C, and E) and moderate (B, D, and F) hypoxia. Values are mean ± standard error of the mean.</p></div

Aldolase C and <i>VEGF</i> mRNA Expression at Different Oxygen Tensions

<p>Lymphocytes were isolated from venous blood taken from CP patients and normal control participants, and incubated at eight different levels of oxygen tension prior to RNA isolation. Gene expression is shown relative to a standard calibrator sample. Basal gene expression at 20% oxygen was significantly higher in CP patients for both <i>Aldolase C</i> (A) and <i>VEGF</i> (B) ( <i>p</i> < 0.05). Both genes were induced by hypoxia, and at the lowest oxygen tension (0.1%) expression was no longer significantly different for either gene. Values are mean ± standard error of the mean. Asterisks indicate <i>p</i> < 0.05 (unpaired <i>t</i>-test). </p

End-Tidal Gas Control, Ventilatory, and Pulmonary Vascular Responses to Mild and Moderate Hypoxia

<div><p>(A and B) End-tidal gas control. </p><p>Pet_O₂</p> and Pet_CO₂ were well controlled. <p>Pet_O₂</p> was well matched between all groups. Pet_CO₂ was lower in the CP patient group, reflecting this group's lower baseline air-breathing Pet_CO₂. <p></p> <p>(C and D) Ventilation, given at body temperature and pressure, saturated with water vapour. Mild hypoxia provoked an increase in ventilation of 4.4 l/min in the CP patients versus 1.6 l/min in normal controls ( <i>p</i> < 0.05), while moderate hypoxia induced increases of 24.5 versus 10.0 l/min in these two groups, respectively ( <i>p</i> < 0.05). </p> <p>(E and F) Pulmonary vascular tone. This was assessed using Doppler echocardiography to determine ΔP_max, a standard non-invasive index of pulmonary vascular tone. With mild hypoxia, ΔP_max increased by 11.5 mm Hg in the CP patient group compared with only 1.1 mm Hg in the normal control group ( <i>p</i> < 0.05). Moderate hypoxia stimulated a rise in ΔP_max of 35.3 mm Hg compared with 6.1 mm Hg in these two groups, respectively ( <i>p</i> < 0.001). </p> <p>All responses are shown during mild (A, C, and E) and moderate (B, D, and F) hypoxia. Values are mean ± standard error of the mean.</p></div