Original Contribution Effects of spinal or general anesthesia on F 2 -isoprostanes and isofurans during ischemia/reperfusion of the leg in patients undergoing knee replacement surgery Emilie Mas a,b, ⁎, Anne E. Barden a,b , Tomas B. Corcoran a,b,c , Michael Phillips d , L. Jackson Roberts II e , Trevor A. Mori a,b a School of Medicine and Pharmacology, University of Western Australia, Perth, WA 6000, Australia b Cardiovascular Research Centre, Royal Perth Hospital, Perth, WA 6000, Australia c Department of Anaesthesia & Pain Medicine, Royal Perth Hospital, Perth, WA 6000, Australia d Western Australian Institute for Medical Research, University of Western Australia, Perth, WA 6000, Australia e Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA abstract article info Article history: Received 26 October 2010 Revised 13 January 2011 Accepted 14 January 2011 Available online 22 January 2011 Keywords: Anesthesia Ischemia/reperfusion Isoprostanes Isofurans Free radicals General and spinal anesthesia are used extensively in orthopedic surgery. However, these methods of anesthesia may result in different amounts of oxygen being delivered to the patient. Ischemia/reperfusion injury after release of the tourniquet initiates free radical-mediated oxidative stress. F 2 -isoprostanes are reliable markers of in vivo lipid peroxidation. However, under conditions of high oxygen tension, isofurans are formed. We aimed to compare plasma isofurans and F 2 -isoprostanes in spinal versus general anesthesia in patients undergoing knee-replacement surgery in a randomized, blinded study. Thirty-nine patients were randomized to spinal (SA; n = 19) or general anesthesia (GA; n = 20). Blood was collected before anesthesia, and a tourniquet was then applied to the limb during surgery. After release of the tourniquet, blood samples were collected at 30 min, 2 h, and 24 h for measurement of plasma F 2 -isoprostanes and isofurans by gas chromatography–mass spectrometry. The two groups were comparable in age and body mass index. Plasma F 2 -isoprostanes were significantly lower in the GA patients compared with the SA patients (p = 0.045). In contrast, the GA patients had significantly elevated plasma isofurans (p = 0.032). Increased isofurans during GA compared with SA are likely to reflect increased oxidative stress due to elevated oxygen concentrations during GA. Further studies are required to assess the implications of these findings on perioperative outcomes. © 2011 Elsevier Inc. All rights reserved. Anesthesia can be generally classified into two main techniques: spinal anesthesia (SA), in which drugs are administered directly into the spinal cord or nerves to provide local blockade of afferent and efferent nerves, or general anesthesia (GA), in which gaseous or intravenous drugs act to induce central neurological depression. There is evidence to suggest that SA reduces the risk of postoperative mortality and morbidity [1]. In an overview of randomized controlled trials, SA was found to confer a significant reduction in postoperative vascular events (deep vein thrombosis, pulmonary embolism, and myocardial infarction), bleeding, and infection (pneumonia) as well as a reduced incidence of respiratory depression and renal failure [1]. The improvement in morbidity has been postulated to be due to an alteration in the surgically induced “stress response” during SA [2]. In orthopedic surgery, the application and release of a tourniquet is often used in elective total knee replacement surgery to reduced blood loss and obtain a clearer surgical field. Ischemia/reperfusion injury (IRI) is one of the main pathophysiological phenomena observed in these procedures. The IRI results in well-defined metabolic and hemodynamic responses to the tourniquet release. These produce a local and systemic inflammatory response characterized by oxidant production, comple- ment activation, leukocyte–endothelial cell adhesion, transendothelial leukocyte migration, platelet–leukocyte aggregation, increased micro- vascular permeability, and decreased endothelium-dependent relaxa- tion [3]. Oxidant production leads to formation of toxic reactive oxygen species (ROS), including superoxide anions (O 2 •- ), hydroxyl radicals (OH • ), hypochlorous acid (HOCl), hydrogen peroxide (H 2 O 2 ), and nitric oxide-derived peroxynitrite [4]. Quantification of products of oxidative damage in biological systems is important to understand the role of free radicals in disease states. Lipids, which undergo peroxidation, are major targets of free radical attack. F 2 -isoprostanes (F 2 -IsoP's) are stable oxidation products of lipid peroxidation [5]. They are prosta- glandin F 2α -like compounds, produced in vivo by nonenzymatic free radical peroxidation of arachidonic acid that is esterified in Free Radical Biology & Medicine 50 (2011) 1171–1176 ⁎ Corresponding author at: School of Medicine and Pharmacology, University of Western Australia, Perth, WA 6000, Australia. Fax: + 61 8 9224 0246. E-mail address: emilie.mas@uwa.edu.au (E. Mas). 0891-5849/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.freeradbiomed.2011.01.021 Contents lists available at ScienceDirect Free Radical Biology & Medicine journal homepage: www.elsevier.com/locate/freeradbiomed