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Effects of CB-VEGF-A Injection in Rat Flap Models for Improved Survival

Akimoto, Minekatsu M.D., Ph.D.; Takeda, Akira M.D., Ph.D.

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Plastic and Reconstructive Surgery: March 2014 - Volume 133 - Issue 3 - p 424e-425e
doi: 10.1097/01.prs.0000438467.44334.fc
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We thank Dr. William C. Lineaweaver and Dr. Feng Zhang for their comments regarding our study, entitled “Effects of CB-VEGF-A Injection in Rat Flap Models for Improved Survival.”1

A large body of work studying the effects of vascular endothelial growth factor (VEGF) on flap survival has been reported and was recently reviewed by Fang et al.2 Various flaps (e.g., epigastric,3,4 dorsal,5 groin,6 and so on) were studied, and VEGF resulted in good results against necrosis of the flaps. Most of the single-flap studies used local administration of recombinant VEGF and various dose concentrations, total doses, and flap sizes; therefore, we think the comparison of those studies with ours of side-by-side double dorsal flaps is difficult, if not impossible, and would, therefore, be meaningless. In the double-flap studies, local and systemic administrations were compared in the same rat.7

We want to investigate and confirm the effect of local administration in the rat’s small body and deny the systemic effect by using the double flap. The difference in the rate of necrosis in the flap in the body of the same individual is most likely due to the effect of the local administration, and this model is the first step toward showing the effect of the Clostridium-derived collagen-binding domain and recombinant VEGF-A164 (CB-VEGF-A) on the flap. We will show the effect of CB-VEGF-A compared with recombinant VEGF in a single-flap model, as has previously been reported by other investigators. We are currently conducting studies using epigastric flaps.

With regard to reporting the effect of CB-VEGF-A for collagen anchoring and angiogenesis for flap survival, we did not think it meaningful to compare this new fusion protein with previous studies. It would be difficult, and maybe even meaningless, to compare these therapies. It was not that we ignored or neglected the recombinant VEGF therapy as reported in previous studies.

Our data showed the angiogenesis and vascular permeability similarity between VEGF and CB-VEGF-A; however, we are currently verifying the data of sustained release to be elucidated in future studies.


The authors have no financial interest to declare in relation to the content of this communication.

Minekatsu Akimoto, M.D., Ph.D.

Akira Takeda, M.D., Ph.D.

Department of Plastic and Aesthetic Surgery

Kitasato University School of Medicine

Kanagawa, Japan


1. Akimito M, Takeda A, Matsushita O, et al. Effects of CB-VEGF-A injection in rat flap models for improved survival. Plast Reconstr Surg. 2013;131:717–725
2. Fang T, Lineaweaver W, Chen M, Kisner C, Zhang F. Effects of vascular endothelial growth factor on survival of surgical flaps: A review of experimental studies. J Reconstr Microsurg. 2014;30:1–14
3. Seify H, Bulky U, Jones G. Effect of vascular endothelial growth factor-induced angiogenesis on TRAM flap harvesting after abdominoplasty. Plast Reconstr Surg. 2003;111:1212–1216
4. Padubidri A, Browne E Jr. Effect of vascular endothelial growth factor (VEGF) on survival of random extension of axial pattern skin flaps in the rat. Ann Plast Surg. 1996;37:604–611
5. Khan A, Ashrafpour H, Huang N, et al. Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: Efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol. 2004;287:R1219–R1229
6. Zhang F, Brooks D, Chen W, Mustain W, Chen MB, Lineaweaver WC. Improvement of venous flap survival by application of vascular endothelial growth factor in a rat model. Ann Plast Surg. 2006;56:670–673
7. Scalise A, Tucci MG, Lucarini G, et al. Local rh-VEGF administration enhances skin flap survival more than other types of rh-VEGF administration: A clinical, morphological and immunohistochemical study. Exp Dermatol. 2004;13:682–690


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