Lower limb ischaemia and reperfusion injury in healthy volunteers measured by oxidative and inflammatory biomarkers.
OBJECTIVE
Ischaemia-reperfusion (IR) injury is partly caused by the release of reactive oxygen species and cytokines and may result in remote organ injury. Surgical patients are exposed to surgical stress and anaesthesia, both of which can influence the IR response. An IR model without these interfering factors of surgery is, therefore, useful to test the potential of antioxidant and cytokine-modulatory treatments. The aim of this study was to characterize a human ischaemia-reperfusion model with respect to oxidative and inflammatory biomarkers.


METHODS
Ten male volunteers were exposed to 20 minutes of lower limb ischaemia. Muscle biopsies and blood samples were taken at baseline and 5, 15, 30, 60 and 90 minutes after tourniquet release and analysed for malondialdehyde (MDA), ascorbic acid, dehydroascorbic acid, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-10, TNF-receptor (TNF-R)I, TNF-RII and YKL-40.


RESULTS
We found no significant increase in MDA in the muscle biopsies after reperfusion. Plasma levels of oxidative and pro- and anti-inflammatory parameters showed no significant differences between baseline and after reperfusion at any sampling time.


CONCLUSIONS
Twenty minutes of lower limb ischaemia does not result in an ischaemia-reperfusion injury in healthy volunteers, measurable by oxidative and pro- and anti-inflammatory biomarkers in muscle biopsies and in the systemic circulation.
Department of Surgery, Herlev Hospital, University of Copenhagen, Herlev, Denmark nathoel@yahoo.dk.
N L
NL
Halladin
Department of Surgery, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
S
S
Ekeløf
Department of Surgery, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
M
M
Alamili
Institute for Inflammation Research, Copenhagen University Hospital, Copenhagen Ø, Denmark.
K
K
Bendtzen
Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
J
J
Lykkesfeldt
Department of Surgery, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
J
J
Rosenberg
Department of Surgery, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
I
I
Gögenur
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007511:Ischemia / Q000150:complications* / Q000503:physiopathology; D035002:Lower Extremity / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018482:Muscle, Skeletal / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000097:blood*; D015424:Reperfusion / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D055815:Young Adult
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D008315:Malondialdehyde
cytokines; inflammatory markers; ischaemia-reperfusion; oxidative stress; pneumatic tourniquet