Inhibition of autophagy after perforator flap surgery increases flap survival and angiogenesis

J Surg Res. 2018 Nov:231:83-93. doi: 10.1016/j.jss.2018.05.018. Epub 2018 Jun 12.

Abstract

Background: The survival ratio of multiterritory perforator flap is variable. Therefore, surviving mechanisms are increasingly explored to identify novel therapeutics. The condition of the choke zone is essential for perforator flap survival. In this study, we investigated autophagy in the choke zone after flap surgery.

Materials and methods: The flap model involved a perforator flap with three territories that was located on the right dorsal side of a rat. A total of 36 rats were divided into six groups, including the control, 0 d postoperative (PO), 1, 3, 5, and 7 d PO groups. In addition, 72 rats were divided into three groups, including a control group, a 3-methyladenine (3-MA) group, and a rapamycin group. Skin tissue of rats was used for measuring autophagy proteins, vascular endothelial growth factor (VEGF) expression, and histological examination. On day 7 after surgery, the survival ratio of each flap was determined.

Results: The expression of autophagy and VEGF in the second choke zone (choke II) was increased after flap surgery. Among the three groups, the survival ratio of flaps in the 3-MA group was the highest. Furthermore, the angiogenesis level in the 3-MA group in choke II was the highest among the three groups.

Conclusions: Autophagy was initiated by surgery in choke II, and VEGF expression in choke II was increased after flap surgery. Inhibiting autophagy after perforator flap surgery is beneficial for flap survival and for promoting angiogenesis in choke II.

Keywords: 3-Methyladenine; CD34; Choke vessel; Plastic reconstructive surgery; Rapamycin; Trauma; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Animals
  • Autophagy*
  • Drug Evaluation, Preclinical
  • Graft Survival / drug effects*
  • Male
  • Microvessels
  • Neovascularization, Physiologic
  • Perforator Flap / blood supply*
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Vascular Endothelial Growth Factor A
  • 3-methyladenine
  • Adenine