Detrimental Effect of Sitagliptin Induced Autophagy on Multiterritory Perforator Flap Survival.

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.

Nobiletin enhances the survival of random pattern skin flaps: Involvement of enhancing angiogenesis and inhibiting oxidative stress.

Random-pattern flap necrosis is a serious challenge for plastic surgeons. Nobiletin (NOB) is a polymethoxylated flavonoid extracted from citrus fruits reported to have antioxidant, anti-inflammatory and anti-apoptotic effects. Our experiment evaluated the impact of NOB on the viability of random flaps. Thirty six male "McFarlane flap" rat models were separated into two equal groups: a control group and an experimental group treated with 10 mg/kg of NOB. After 7 days, the range of necrosis was calculated, and a histological analysis was performed on tissue specimens. Immunohistochemical staining, lead oxide-gelatin angiography, and a Laser Doppler perfusion imager were used to assess angiogenesis and measure oxidative stress, as indicated by superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels. The average survival area of flap was greater in the NOB-treated group than that in the control group. The NOB-treated group mitigated oxidative stress via augmented SOD, reduced MDA, and enhanced vascular endothelial growth factor (VEGF) expression. Hematoxylin and eosin staining indicated that NOB increased blood flow and had anti-inflammatory effects. Our findings revealed that NOB improved random skin flap survival.

Trehalose promotes the survival of random-pattern skin flaps by TFEB mediated autophagy enhancement.

Random-pattern skin flaps are commonly used and valuable tools in reconstructive surgery, however, post-operative random skin flap necrosis remains a major and common complication. Previous studies have suggested that activating autophagy, a major pathway for degradation of intracellular waste, may improve flap survival. In this study, we investigated whether trehalose, a novel and potent autophagy activator, improves random skin flap viability. Our results demonstrated that trehalose significantly improves viability, augments blood flow, and decreases tissue edema. Furthermore, we found that trehalose leads to increased angiogenesis, decreased apoptosis, and reduced oxidative stress. Using immunohistochestry and western blot, we demonstrated that trehalose augments autophagy, and that inhibition of autophagy augmentation using 3MA significantly blunted the aforementioned benefits of trehalose therapy. Mechanistically, we showed that trehalose's autophagy augmentation is mediated by activation and nuclear translocation of TFEB, which may be due to inhibition of Akt and activation of the AMPK-SKP2-CARM1 signaling pathway. Altogether, our results established that trehalose is a potent agent capable for significantly increasing random-pattern skin flap survival by augmenting autophagy and subsequently promoting angiogenesis, reducing oxidative stress, and inhibiting cell death.

Allogenic endothelial progenitor cell transplantation increases flap survival through an upregulation of eNOs and VEGF on venous flap survival in rabbits.

BACKGROUND: Endothelial progenitor cells (EPCs) are one type of bone marrow hematopoietic stromal cells which play a vital role in neovascularization and tissue repair. In this study, we investigated whether EPCs promote flap survival in a rabbit venous model. MATERIALS AND METHODS: EPCs were customized from CHI Scientific, Inc, China. Thirty-six rabbits were randomly assigned to either the sham group (n = 12), the control group (n = 12) or the EPC transplantation group (n = 12). A 10 × 6 cm venous flap was created on the rabbit abdomen. Both the EPC transplantation and control groups had the same volume of EPCs-PBS (phosphate buffered saline) and PBS on postoperative day 1. Flap survival, blood flow, histopathology, expression of endothelial nitric oxide synthase (eNOs) and Vascular Endothelial Growth Factor (VEGF) were detected on postoperative day 10. RESULTS: Cellular immunofluorescence assay positively confirmed that the EPCs were undergoing differentiation. The survival rate of the flap in the EPC transplantation group was 58.4 ± 7.1%, which was significantly higher than that of the control group (4.8 ± 3.4%) (p<0.01). Histological examination revealed that the EPC transplantation group had higher microvessel density, fewer inflammatory cells, and a higher expression of eNOs and VEGF. Significantly increased blood flow perfusion was seen in the EPC transplantation group using laser Doppler imaging. The Western Blot technique revealed that the expression of eNOs and VEGF in the EPC transplantation group were both significantly higher than those in the control group. CONCLUSION: This study demonstrated that EPC transplantation improved venous flap survival in rabbits. The present findings may provide insight into the promotion of venous flap survival in clinical practice in the future.

Effects of pedicle torsion on dynamic perforasome survival in a multiterritory perforator flap model: An experimental study.

BACKGROUND: Necrosis of propeller flaps is a problem in clinical practice. This study was performed to investigate the effects of pedicle torsion on dynamic perforasome survival using a multiterritory perforator flap model in rats. METHODS: Intercostal artery perforator flaps (IC flaps) containing two adjacent dynamic perforasomes were applied to both sides of the dorsum in 15 rats. The IC vessels were dissected carefully under 10 × magnification. A 360° arc of pedicle torsion was applied to the right IC flaps, which comprised the rotary group. Left IC flaps were used as controls. Flap perfusion, viability, and angiography were compared between the two groups. RESULTS: Sodium fluorescein angiography showed that there was blood supply to the flap in both groups on postoperative day (POD) 1, and laser Doppler images indicated that flap perfusion increased daily after surgery. The differences in perfusion of dynamic perforasomes between the two groups were not significant. The mean survival rate of the rotary group was not significantly different from that of the control group (98.94 ±â€¯1.24% versus 99.03 ±â€¯1.86%, respectively, p > 0.05) on POD 7. Angiography showed that dilated choke vessels connected the three perforasomes in both groups. CONCLUSIONS: The 360° arc of pedicle torsion had no detrimental effect on dynamic perforasome perfusion or survival in a multiterritory perforator flap model after meticulous surgical dissection of the pedicle in this study. The dilated choke vessel connected adjacent perforasomes, and the dynamic perforasome survival still adhered to the perforasome theory after pedicle torsion.