title: Controlled moderate hypovolaemia in healthy volunteers is not associated with the development of oxidative stress assessed by plasma F2-isoprostanes and isofurans.
abstract: Hypovolaemia can be associated with substantial morbidity, particularly when it occurs in the setting of trauma and in patients with comorbid diseases. Hypovolaemia and inflammation such as occur in the setting of trauma and surgery, are associated with systemic oxidative stress and free-radical injury. Free-radical injury that results from hypovolaemia-induced organ reperfusion may further augment inflammatory processes. It is unknown exactly what proportion of free-radical injury is associated with isolated hypovolaemia as opposed to the contribution from inflammation from surgery or trauma. In the first human study of its kind, we exposed 8 adult male volunteers to venesection-induced hypovolaemia in progressive aliquots of 5% of total blood volume until 20% had been removed. This blood was subsequently reinfused. Plasma F2-isoprostanes and isofurans, markers of in vivo lipid oxidation, were measured by gas chromatography-mass spectrometry at each 5% aliquot venesected and at each 5% reinfused. Between baseline and maximal blood loss there was a minor fall in haemoglobin concentration from 143.9g/l to 138.8g/l (p=0.004, 95% CI 2.2, 8.0g/L). No significant change from baseline occurred in the concentrations of either plasma F2-isoprostanes or isofurans during venesection (p=0.116 and p=0.152, respectively) or blood reinfusion (p=0.553 and p=0.736, respectively). We can conclude that in healthy adult volunteers, isolated hypovolaemia to 20% total blood volume loss is not associated with detectable systemic oxidative stress. The free-radical injury identified in surgical and trauma patients may represent the effects of tissue damage and inflammation, with an uncertain contribution from tissue ischemia as may occur with hypovolaemia.
authors.affiliation: Department of Anaesthesia & Pain Medicine, Royal Perth Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Tomas B
authors.initials: TB
authors.lastname: Corcoran
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mas
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia. Electronic address: anne.barden@uwa.edu.au.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Barden
authors.affiliation: Dept of Pharmacology, Vanderbilt University, Nashville, USA.
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia; Department of Anaesthesia, Fremantle Hospital, Fremantle, Western Australia, Australia.
authors.forename: Edmond
authors.initials: E
authors.lastname: O'Loughlin
mesh_terms: D000328:Adult; D028441:F2-Isoprostanes / Q000097:blood*; D005609:Free Radicals / Q000097:blood; D005663:Furans / Q000097:blood; D064368:Healthy Volunteers; D006801:Humans; D020896:Hypovolemia / Q000097:blood* / Q000209:etiology / Q000473:pathology; D007249:Inflammation / Q000097:blood* / Q000473:pathology; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D018384:Oxidative Stress; D018962:Phlebotomy / Q000009:adverse effects; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications / Q000601:surgery
chemical_list: D028441:F2-Isoprostanes; D005609:Free Radicals; D005663:Furans; C039281:furan
keywords: Human; Injury; Lipid peroxidation; Surgery; Venesection