title: Reperfusion injury in the human forearm is mild and not attenuated by short-term ischaemic preconditioning.
abstract: 1. Ischaemia-reperfusion (IR) injury is an important contributor to tissue damage and has been shown to be attenuated by preconditioning (PC) in some animal models. A recent report has suggested that the forearm can be used for the study of this phenomenon in humans. We aimed to reproduce and further characterize this model. 2. Healthy young adult volunteers (mean (+/-SEM) age 32+/-6 years) were studied on two occasions. During one visit, IR alone was induced by 10 min of upper arm cuff occlusion, whereas on another occasion a PC stimulus (three 3 min cuff inflations) preceded IR. Endothelial function in the ischaemic arm was assessed by measuring arterial flow-mediated dilatation (FMD) and by calculation of forearm blood flow at baseline and 15 and 60 min after IR. Systemic venous blood was sampled from the non-ischaemic arm at baseline, after PC and at 2, 15 and 30 min after IR to assess neutrophil/leucocyte (CD11b) and platelet (bound glycoprotein IIb/IIIa and fibrinogen) activation, as well as numbers of platelet-leucocyte complexes, which were determined by flow cytometry. Because of a lack of measurable effects, the IR experiment was repeated with 20 min ischaemia in six subjects. 3. Five females and eight males completed the study. Flow-mediated dilatation was significantly impaired 30 min after IR (4.1 vs 6.2% at baseline; P<0.05);however, this was not significantly attenuated by ischaemic PC (FMD reduction at 30 min compared with baseline was 2.1+/-0.5% with IR alone and 2.6+/-1.4% with IR after PC; NS). No significant effect was seen on the number of platelet-leucocyte aggregates or on white cell or platelet activation after IR alone or after IR with PC (P>0.6 for all comparisons). Similar results were obtained in six subjects studied subjected to 20 min ischaemia. 4. In conclusion, in healthy young adults, brief periods of skeletal muscle ischaemia lead to arterial endothelial dysfunction, but no significant platelet or white cell activation. Preconditioning does not attenuate this effect on the endothelium. Further experiments with longer ischaemia times and varying PC stimuli may be necessary to produce measurable effects; however, this may prove difficult in conscious human subjects.
authors.affiliation: The Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors.forename: J G
authors.initials: JG
authors.lastname: Kilian
authors.forename: S
authors.initials: S
authors.lastname: Nakhla
authors.forename: K
authors.initials: K
authors.lastname: Griffith
authors.forename: J
authors.initials: J
authors.lastname: Harmer
authors.forename: M
authors.initials: M
authors.lastname: Skilton
authors.forename: D S
authors.initials: DS
authors.lastname: Celermajer
mesh_terms: D000328:Adult; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D005542:Forearm / Q000098:blood supply* / Q000503:physiopathology*; D006801:Humans; D019194:Ischemic Preconditioning; D007962:Leukocytes / Q000502:physiology; D008262:Macrophage Activation / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control*; D014664:Vasodilation / Q000502:physiology