Clinical iron deficiency disturbs normal human responses to hypoxia

摘要: BACKGROUND. Iron bioavailability has been identified as a factor that influences cellular hypoxia sensing, putatively via an action on the hypoxia-inducible (HIF) pathway. We therefore hypothesized clinical iron deficiency would disturb integrated human responses to hypoxia. METHODS. performed prospective, controlled, observational study of effects status hypoxic pulmonary hypertension. Individuals with absolute (ID) and iron-replete (IR) control group were exposed two 6-hour periods isocapnic hypoxia. The second exposure was preceded by i.v. infusion iron. Pulmonary artery systolic pressure (PASP) serially assessed Doppler echocardiography. RESULTS. Thirteen ID individuals completed age- sex-matched controls. PASP did not differ or day before each exposure. During first exposure, rise in 6.2 mmHg greater (absolute rises 16.1 10.7 mmHg, respectively; 95% CI for difference, 2.7–9.7 P = 0.001). Intravenous attenuated both groups; however, effect participants than controls reductions 11.1 6.8 difference change, –8.3 –0.3 0.035). Serum erythropoietin also differed between groups. CONCLUSION. Clinical disturbs normal hypoxia, evidenced exaggerated hypertension is reversed subsequent administration. Disturbed sensing signaling provides mechanism through which may be detrimental health. TRIAL REGISTRATION. ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT01847352","term_id":"NCT01847352"}}NCT01847352). FUNDING. M.C. Frise recipient British Heart Foundation Research Training Fellowship (FS/14/48/30828). K.L. Dorrington supported Dunhill Medical Trust (R178/1110). D.J. Roberts R&D funding from National Health Service (NHS) Blood Transplant Institute (NIHR) Programme grant (RP-PG-0310-1004). This research funded NIHR Oxford Biomedical Centre Programme.