Abstract
Multiterritory perforator flap survival is commonly applied in surgical tissue reconstructions and covering of large skin defects. However, multiple risk factors such as ischemia, reperfusion injury, and apoptosis after reconstructive surgeries cause necrosis in distal parts with outcomes ranging from poor aesthetic appearance to reconstructive failure. A few studies have reported that sitagliptin (Sit) promotes angiogenesis and inhibits apoptosis. However, little is known about Sit-induced autophagy especially on the flap model. Therefore, our study investigated the effect of Sit and its induced autophagy on the perforator flap survival. Ninety male Sprague-Dawley rats were randomly separated into control, Sit, and Sit+3-methyladenine group. Results revealed that Sit significantly promoted flap survival by enhancing angiogenesis, reducing oxidative stress, and attenuating apoptosis. In addition, flap survival was further improved after co-administration with 3-methyladenine to inhibit autophagy. Overall, our results established that Sit has positive effects in promoting survival of multiterritory perforator flap. Sit-induced autophagy was detrimental for flap survival and its inhibition may further improve flap survival.
Highlights
Multiterritory perforator flap have been widely used in clinics for a long time to repair skin defects such as congenital disorders, trauma, tumor ablation, and diabetic foot ulcer (Cheng et al, 2017)
Blood supply from the pedicle is consumed after crossing the first choke zone, which results in the failure of blood flow to continue to cross the Sitagliptin Promotes Flap Survival second choke zone, leading to ischemia in the potential territory in early stage (Wang et al, 2017b)
Tissue water content on the 7th postoperative days (PODs) was significantly higher in the control group than in the Sit group, with the lowest tissue water content recorded in the Sit +3MA group (Figures S2A, B)
Summary
Multiterritory perforator flap have been widely used in clinics for a long time to repair skin defects such as congenital disorders, trauma, tumor ablation, and diabetic foot ulcer (Cheng et al, 2017). Previous studies have revealed that necrosis usually occurs away from the boundary between potential and dynamic territory (Taylor et al, 1992; Fichter et al, 2016). Blood supply from the pedicle is consumed after crossing the first choke zone, which results in the failure of blood flow to continue to cross the Sitagliptin Promotes Flap Survival second choke zone, leading to ischemia in the potential territory in early stage (Wang et al, 2017b). Angiogenesis and choke vessel's dilation in the second choke zone causing the reperfusion injury in the potential territory. Ischemia-reperfusion (I/R) brings a burst of reactive oxygen species (ROS) aggregated and cell apoptosis increased (Suzuki et al, 2008; Sies et al, 2017). It's necessary to find an effective way to enhance multiterritory perforator flap survival
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