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

Kamat P, Juon B, Jossen B, Gajanayake T, Rieben R, Vögelin E - J Inflamm (Lond) (2012)

Bottom Line: A tourniquet was placed on the upper arm and inflated to 250 mmHg for 116 ± 16 min, during which the surgery was performed.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Research, University of Bern, Murtenstrasse 50 3008, Bern, Switzerland. robert.rieben@dkf.unibe.ch.

ABSTRACT

Background: Activation 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.

Methods: Ten 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.

Results: Markers 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.

Conclusions: In 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.

No MeSH data available.


Related in: MedlinePlus

Plasma levels of creatine kinase MM. CK-MM was measured by ELISA and found to be significantly higher at the end of ischemia (0 min reperfusion) as compared to baseline. Levels dropped again during the reperfusion phase, but were still higher than baseline after 10 min reperfusion (as shown by Bonferroni’s post test for Repeated Measures ANOVA), n = 10.
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Figure 7: Plasma levels of creatine kinase MM. CK-MM was measured by ELISA and found to be significantly higher at the end of ischemia (0 min reperfusion) as compared to baseline. Levels dropped again during the reperfusion phase, but were still higher than baseline after 10 min reperfusion (as shown by Bonferroni’s post test for Repeated Measures ANOVA), n = 10.

Mentions: Creatine kinase-MM was measured in plasma samples as a marker for skeletal muscle injury. Figure 7 shows each patient as an individual dot and the mean represented by a dash at every time point. The values given below are mean ± standard deviation. CK-MM values increased significantly from 2066 ± 1122 U/L at baseline to 5908 ± 1843 U/L at 0 min reperfusion (p < 0.001). At 2 min reperfusion the levels significantly dropped from 0 min reperfusion to 3504 ± 1855 U/L (p < 0.001). However, at 10 min reperfusion, CK-MM levels (4296 ± 1894 U/L) were still higher than at baseline (p < 0.01).


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

Kamat P, Juon B, Jossen B, Gajanayake T, Rieben R, Vögelin E - J Inflamm (Lond) (2012)

Plasma levels of creatine kinase MM. CK-MM was measured by ELISA and found to be significantly higher at the end of ischemia (0 min reperfusion) as compared to baseline. Levels dropped again during the reperfusion phase, but were still higher than baseline after 10 min reperfusion (as shown by Bonferroni’s post test for Repeated Measures ANOVA), n = 10.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3404016&req=5

Figure 7: Plasma levels of creatine kinase MM. CK-MM was measured by ELISA and found to be significantly higher at the end of ischemia (0 min reperfusion) as compared to baseline. Levels dropped again during the reperfusion phase, but were still higher than baseline after 10 min reperfusion (as shown by Bonferroni’s post test for Repeated Measures ANOVA), n = 10.
Mentions: Creatine kinase-MM was measured in plasma samples as a marker for skeletal muscle injury. Figure 7 shows each patient as an individual dot and the mean represented by a dash at every time point. The values given below are mean ± standard deviation. CK-MM values increased significantly from 2066 ± 1122 U/L at baseline to 5908 ± 1843 U/L at 0 min reperfusion (p < 0.001). At 2 min reperfusion the levels significantly dropped from 0 min reperfusion to 3504 ± 1855 U/L (p < 0.001). However, at 10 min reperfusion, CK-MM levels (4296 ± 1894 U/L) were still higher than at baseline (p < 0.01).

Bottom Line: A tourniquet was placed on the upper arm and inflated to 250 mmHg for 116 ± 16 min, during which the surgery was performed.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Research, University of Bern, Murtenstrasse 50 3008, Bern, Switzerland. robert.rieben@dkf.unibe.ch.

ABSTRACT

Background: Activation 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.

Methods: Ten 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.

Results: Markers 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.

Conclusions: In 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.

No MeSH data available.


Related in: MedlinePlus