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Updated: Jun 2, 2026
Ischemic Tissue Injury in the Dorsal Skinfold Chamber of the Mouse: A Skin Flap Model to Investigate Acute Persistent Ischemia
Published on: November 17, 2014
Monitoring molecular changes induced by ischemia/reperfusion in human free muscle flap tissue samples
Steffen U Eisenhardt1, Yvonne Schmidt, Gezim Karaxha
1Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Freiburg, Germany. steffen.eisenhardt@uniklinik-freiburg.de
Background:
Our current knowledge of the pathophysiological sequelae of ischemia or reperfusion (I/R) injury in free tissue transfer in reconstructive surgery is based on data obtained in animal experiments. In this study, we investigated the histologic and molecular changes after 11 free microsurgical muscle transfers in human muscle tissue.
Methods:
Biopsies of free muscle flap tissue were taken immediately before clipping of the pedicle and 5 days after ischemia and successful microanastomosis and restoration of the blood flow. Samples were analyzed histologically for edema formation and by immunohistochemistry for infiltration of inflammatory cells and angiogenesis. Expression levels of the inflammatory marker proteins interleukin-1β and tumor necrosis factor α and of complement component 3 as a major mediator of I/R injury were analyzed by real-time polymerase chain reaction. A TUNEL (terminal desoxynucleotidyl transferase-mediated-dUTP-nick-end-labeling) assay was used to assess apoptosis levels within the human muscle tissue.
Results:
I/R injury leads to a significant up-regulation of inflammatory parameters, infiltration of inflammatory cells, and angiogenesis. Increased complement component 3 deposition and apoptosis of cells were accompanied by interstitial edema as indication for a pronounced postischemic inflammatory reaction within the muscle tissue after free tissue transfer.
Conclusions:
Our findings of molecular changes induced by I/R injury in human striated muscle tissue validate data obtained in animal models of I/R injury. The parameters and inflammatory patterns defined in this study will allow for the monitoring of the success of novel pharmaceutical strategies in the future and will help to transfer data obtained in animal work to the in vivo setting in human beings.
