Effect of Endothelial Growth Factor on Flap Surgical Delay.

Abstract

Sir: We read with great interest the article by Jiang et al. entitled “Effect of Endogenous Vascular Endothelial Growth Factor on Flap Surgical Delay in a Rat Flap Model.”1 This article reported increasing endogenous vascular endothelial growth factor (VEGF) concentration in the choke zones with improved choke vessel dilation and neovascularization in surgical delay phenomenon. Although the endogenous VEGF was decreased by its inhibitor, the survival area of the delayed flaps did not improve. In conclusion, endogenous VEGF was an initiating factor in the surgical delay by regulating choke vessel dilation and neovascularization within the choke zones. Inspired by the authors, we would like to express our considerations on this study. First, when evaluating the VEGF inhibition efficiency in a delayed flap, the authors divided the rats into only the delay group and the VEGF inhibition group. In the VEGF inhibition group, regardless of the pharmacologic effect of axitinib, the procedure of subcutaneous injection should be considered as an independent experimental intervention and potentially disturbed the choke vessel dilation and concentration of endogenous VEGF. Therefore, an additional blank group should be set to control this confounding factor. Second, when the endogenous VEGF was decreased by its inhibitor, the expression of downstream signaling proteins (e.g., p-Akt, Bcl-2, HIF-1α, and Bax) was detected with Western blot assay. However, the alteration of the expression of proteins just partially demonstrated the situation. The change of relative mRNA expression and quantification of different histologic cells with positive expression of those proteins can also be included. Besides, previous studies have proved that downstream proteins, such as HIF-1α, played a double-acting role in the regulation of cell apoptosis. In a mild hypoxic environment, HIF-1α can inhibit apoptosis by reducing the ratio of Bax/Bcl-2 and caspase-3 activity.2,3 Although the tissue undergoes severe hypoxia, HIF-1α can promote cell apoptosis by means of the p53 pathway. Therefore, the ratio of Bax to Bcl-2 and caspase-3 activity can also be included to elaborate a potential mechanism of VEGF in a surgical delayed flap. Third, the number of transverse vessels across the choke zone was counted in the postmortem arteriograph to assess the choke vessel dilation. Nevertheless, the postmortem arteriograph was still quite different from the situation in vivo after perfusion with lead oxide gelatin. The previous study of Zhuang et al. may provide a good reference for the choke vessel observation in vivo.4 They documented a novel skinfold chamber technique for the study of choke anastomotic vessels in a rat skin flap model. Through the skinfold chamber, the morphologic alteration of choke vessels can be observed dynamically, and measurements of vessel diameter, dilation, and blood flow velocity can be performed up to 8 days with the stereomicroscope. ACKNOWLEDGMENTS Grants from the Capital Foundation of Medical Development (2016-2-4-41) and CAMS Initiative for Innovative Medicine (CAMS-12M) were received for this article. DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication. Yiye Ouyang, M.D.Chengcheng Li, M.D.Xingyi Du, M.D.Chunjun Liu, M.D.Plastic Surgery Hospital (Institute)Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijing, People’s Republic of China