Assessment of endothelium and inflammatory response at the onset of reperfusion injury in hand surgery

Abstract

BackgroundActivation of the endothelium, complement activation and generation of cytokines are known events during ischemia-reperfusion (I/R) that mediate tissue injury. Our aim was to elucidate their respective participation at the onset of the reperfusion phase. Tourniquet application in hand surgery causes short-term ischemia, followed by reperfusion and was therefore used as the model in this study.MethodsTen patients were included in the study after obtaining informed consent. A tourniquet was placed on the upper arm and inflated to 250 mmHg for 116 ± 16 min, during which the surgery was performed. Venous blood and tissue samples from the surgical area were taken at baseline as well as 0, 2, and 10 min after reperfusion and analyzed for the following parameters: Endothelial integrity and/or activation were analyzed by measuring heparan sulfate and syndecan-1 in serum, and vWF, heparan sulfate proteoglycan as well as CD31on tissue. Complement activation was determined by C3a and C4d levels in plasma, levels of C1-inhibitor in serum, and IgG, IgM, C3b/c, and C4b/c deposition on tissue. Cytokines and growth factors IL-5, IL-6, IL-7, IL-8, IL-10, IL-17, G-CSF, GM-CSF, MCP-1, TNFα, VEGF, and PDGF bb were measured in the serum. Finally, CK-MM levels were determined in plasma as a measure for muscle necrosis.ResultsMarkers for endothelial activation and/or integrity as well as complement activation showed no significant changes until 10 min reperfusion. Among the measured cytokines, IL-6, IL-7, IL-17, TNFα, GM-CSF, VEGF, and PDGF bb were significantly increased at 10 min reperfusion with respect to baseline. CK-MM showed a rise from baseline at the onset of reperfusion (p < 0.001) and dropped again at 2 min (p < 0.01) reperfusion, suggesting ischemic muscle damage.ConclusionsIn this clinical model of I/R injury no damage to the endothelium, antibody deposition or complement activation were observed during early reperfusion. However, an increase of pro-inflammatory cytokines and growth factors was shown, suggesting a contribution of these molecules in the early stages of I/R injury.

Revascularization and muscle adaptation to limb demand ischemia in diet-induced obese mice

“…The biological significance of IL-7 increase in demand ischemia is not clear. However, in humans, enhanced IL-7 release was reported after hand surgery [34]. A major role for IL-7 has been described in lymphocytes maintenance [35].…”

Tourniquet-induced ischemia-reperfusion injuries during extremity surgery at children's age: impact of anesthetic chemical structure

“…Mechanisms underlying IR injury have been studied extensively and are known to engage a spectrum of pathways. 1 Since surgical trauma not only intensifies the oxidative stress by generating reactive oxygen species (ROS), but also weakens the biological defense system against ROS attack, the effects of anesthesia techniques on IR injury are of considerable scientific and clinical interest because anesthetics with anti-oxidant properties or free radical-scavenging activity could offer considerable protection and benefits in this setting. 2 Propofol anesthesia seems to enhance the antioxidant capacity against tourniquet-induced IR injury.…”

<p>MicroRNA-579-3p Exerts Neuroprotective Effects Against Ischemic Stroke via Anti-Inflammation and Anti-Apoptosis</p>

“…Another important mechanism, which leads to toxic enzyme activation, free radical overload, etc., causes a series of tissue lesions. 11, Therefore, it is speculated that in the treatment of cerebral I/R injury, intervention anti-apoptosis and anti-inflammatory may be a potentially effective measure.…”