Ischemia-Reperfusion Injury Leads to Significant Tissue Damage in Free Flap Surgery

Abstract

Sir:FigureWe read with great interest the article entitled “Expression of HIF-1α in Ischemia and Reperfusion in Human Microsurgical Free Muscle Tissue Transfer” by Dragu et al. (Plast Reconstr Surg. 2011;127:2293–2300). We agree that our current knowledge of the mechanisms of ischemia-reperfusion injury in reconstructive microsurgery is based mainly on animal models, and the evaluation of the related mechanisms in human tissue is a long-neglected necessity. The hypothesis that hypoxia-inducible factor (HIF)-1α levels could be elevated in ischemia-reperfusion in human free flap tissue and could be of pathophysiologic consequence is reasonable, especially considering the regulation of HIF-1α by reactive oxygen species1 that play a pivotal role in ischemia-reperfusion injury.2 Therefore, the results of this well-executed study, at least with regard to the immunohistologic data, are unexpected but will add to our understanding of the ischemia-reperfusion–related molecular changes in free flap surgery that occur at early stages of ischemia-reperfusion injury. However, the data presented by the authors do not allow for the conclusion “that the accepted times of ischemia, generally up to 90 minutes, are not sufficient to induce pathophysiologic processes, which can ultimately lead to flap loss,” which is rebutted by our own data. We showed in our recent work that ischemia-reperfusion injury in human free flap tissue leads not only to significant infiltration of leukocytic cells and expression of the proinflammatory parameters tumor necrosis factor-α and interleukin-1β, but also to a significant increase in interstitial edema and apoptosis,3 thereby opposing the conclusion of Dragu et al. In contrast to the work of Dragu et al., who examined the effects of ischemia-reperfusion on free flap tissue 77 ± 22 minutes after ischemia-reperfusion, we examined free flap tissue before ischemia and 5 days after ischemia-reperfusion to allow enough time for the most relevant morphologic and molecular tissue changes to occur. Interestingly, the authors previously reported no changes of apoptotic parameters in free flap tissue when biopsy specimens were obtained intraoperatively after ischemia-reperfusion4 in an approach very similar to the one presented in the article under discussion. These major differences in our work seem to be related to the different time points of biopsy, and it remains doubtful whether all ischemia-reperfusion–relevant molecular changes can be detected within the short period allowed by Dragu et al. This could potentially also apply to the results obtained for HIF-1α levels and should be taken into account when interpreting the results presented in this elegant study. Yvonne Schmidt, M.D. Holger Bannasch, M.D. Steffen U. Eisenhardt, M.D. Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Freiburg, Germany