AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay

Gersch, Robert P.; Fourman, Mitchell S.; Phillips, Brett T.; Nasser, Ahmed; McClain, Steve A.; Khan, Sami U.; Dagum, Alexander B.; Bui, Duc T.

doi:10.1097/gox.0000000000000453

Cited by 5 publications

(1 citation statement)

References 25 publications

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“…Future efforts to improve tissue viability and achieve maximal clinical benefits may include the combination of BSD with pharmacological intervention 21 – 24 and/or gene therapy intervention. 25 – 27 …”

Section: Discussionmentioning

confidence: 99%

The Delay Phenomenon: Is One Surgical Delay Technique Superior?

Gersch

Fourman

Dracea

et al. 2017

Plastic and Reconstructive Surgery - Global Open

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Background:Surgical delay remains a common method for improving flap survival. However, the optimal surgical technique has not been determined. In this article, we compare flap perfusion, viable surface area, and flap contraction of 2 surgical delay techniques.Methods:Male Sprague-Dawley rats were divided into 3 groups. In the incisional surgical delay group (n = 9), a 9 × 3 cm dorsal flap was incised on 3 sides without undermining, leaving a cranial pedicle. In the bipedicle surgical delay group (BSD, n = 9), a 9 × 3 cm dorsal flap was incised laterally and undermined, leaving cranial and caudal pedicles. Control group (n = 16) animals did not undergo a delay procedure. Ten days following surgical delay, all flaps for all groups were raised, leaving a cranial pedicle. A silicone sheet separated the flap and the wound bed. On postoperative day (POD) 7, viable surface area was determined clinically. Contraction compared to POD 0 was measured with ImageJ software. Perfusion was measured with Laser Doppler Imaging. The Kruskal-Wallis with Dunn’s multiple comparisons test was performed for group comparisons.Results:BSD preserved significantly more viable surface area on POD 7 (13.7 ± 4.5 cm2) than Control (8.7 ± 1.8 cm2; P = 0.01). BSD also showed significantly less contraction (21.0% ± 13.5%) than Control (45.9% ± 19.7%; P = 0.0045). BSD and incisional surgical delay showed significantly increased perfusion compared with Control on POD 0 (P = 0.02 and 0.049, respectively), which persisted on POD 3. This trend resolved by POD 7.Conclusion:BSD showed improved early perfusion, increased viable surface area, and reduced contraction compared to control, suggesting that BSD is the superior flap design for preclinical modeling.

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Section: Discussionmentioning

confidence: 99%

The Delay Phenomenon: Is One Surgical Delay Technique Superior?

Gersch

Fourman

Dracea

et al. 2017

Plastic and Reconstructive Surgery - Global Open

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Perioperative Treatment with a Prolyl Hydroxylase Inhibitor Reduces Necrosis in a Rat Ischemic Skin Flap Model

Sergesketter

Cason

Ibrahim

et al. 2019

Plastic &Amp; Reconstructive Surgery

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Background: The hypoxia-inducible factor (HIF) pathway, regulated by prolyl hydroxylase, is central to tissue adaptation to ischemia. The authors tested whether the prolyl hydroxylase inhibitor dimethyloxalylglycine reduces skin flap necrosis. Methods: Dorsal skin flaps were raised on hairless rats, with dimethyloxalylglycine delivered intraperitoneally and/or topically for 7 days before and after surgery. After 14 treatment days, percentage of flap necrosis was compared grossly and tissue perfusion compared with an in vivo imaging system. Angiogenesis was compared using immunohistochemical CD31 staining and enzyme-linked immunosorbent assay for tissue vascular endothelial growth factor. Expression levels of HIF-1α and terminal deoxynucleotidyl transferase-mediated dUDP end-labeling were compared using immunohistochemical staining. Complete blood counts and gross necropsy specimens were obtained to assess systemic toxicity. Results: Dimethyloxalylglycine administration significantly improved postoperative flap viability, with combined topical and intraperitoneal dimethyloxalylglycine administration leading to reduced necrosis on postsurgical day 7 at 6 mg/kg/day, 12 mg/kg/day, 24 mg/kg/day, and 48 mg/kg/day versus controls (all p < 0.05). Compared with controls (unperfused, 39.9 ± 3.8 percent), dimethyloxalylglycine treatment led to a dose-dependent decrease in unperfused tissue at 6 mg/kg/day (11.4 ± 1.7 percent), 12 mg/kg/day (9.4 ± 4.2 percent), 24 mg/kg/day (4.7 ± 2.6 percent), and 48 mg/kg/day (1.4 ± 0.9 percent) (all p < 0.001). Topical dimethyloxalylglycine application alone administered at 48 mg/kg/day was sufficient to improve flap viability (p = 0.005). Dimethyloxalylglycine-treated flaps exhibited higher CD31 staining (p = 0.004), tissue vascular endothelial growth factor (p = 0.007), HIF-1α staining (p < 0.001), and reduced terminal deoxynucleotidyl transferase-mediated dUDP end-labeling staining (p = 0.045). There were no differences in hematocrit or macroscopic organ changes on gross necropsy. Conclusion: Topical and systemic targeting of the HIF-1 pathway may be a promising therapeutic approach to improve flap resistance to ischemia.

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Hypoxia-Inducible Factor-1α Potentiates Multiterritory Perforator Flap Survival by Augmenting Vascular Endothelial Growth Factor Expression in the Choke II Zone

Zeng,

Xie,

Guo

et al. 2024

Ann Plast Surg

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Background Hypoxia-inducible factor-1α (HIF-1α), regulated by prolyl hydroxylase, plays a central role in tissue adaptation to ischemia. This study investigates the impact of HIF-1α on angiogenesis in the Choke II zone of multiterritory perforator flaps. Methods Ninety male Wistar rats were allocated into 3 groups, with 30 rats in each group: the dimethyloxalylglycine (DMOG) group, the 3-(5-hydroxymethyl-2-furyl)-1-benzylindazole (YC-1) group, and the normal saline (NS) group. All rats underwent multiterritory perforator flap surgeries on their dorsal side. Subsequently, they received intraperitoneal injections of DMOG (40 mg/kg), YC-1 (10 mg/kg), and normal saline on postoperative days 1, 2, and 3, respectively. After treatment, angiogenesis in the Choke II zone of the flap on day 7 was observed through transillumination tests and lead oxide/gelatin x-ray angiography. Histological features were determined using hematoxylin and eosin staining, and the expression of HIF-1α and vascular endothelial growth factor (VEGF) in the Choke II region of the flap was assessed via immunohistochemistry and western blotting. Results Compared to the YC-1 and NS groups, the DMOG group exhibited significant angiogenesis, resulting in a denser vascular network in the Choke II zone of the flap. The DMOG group showed significantly higher microvessel density in the Choke II zone than the YC-1 and NS groups (7.10 ± 0.99 vs 24.30 ± 3.65; 14.30 ± 2.40 vs 24.30 ± 3.65, both P<0.05). Additionally, the DMOG group demonstrated higher expression of VEGF and HIF-1α in the flaps than the other groups (P < 0.05). Conclusions In summary, HIF-1α enhances the expression of VEGF, promoting angiogenesis in the Choke II zone of the multiterritory perforator flap, thus increasing the survival area.

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AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay

Cited by 5 publications

References 25 publications

The Delay Phenomenon: Is One Surgical Delay Technique Superior?

The Delay Phenomenon: Is One Surgical Delay Technique Superior?

Perioperative Treatment with a Prolyl Hydroxylase Inhibitor Reduces Necrosis in a Rat Ischemic Skin Flap Model

Hypoxia-Inducible Factor-1α Potentiates Multiterritory Perforator Flap Survival by Augmenting Vascular Endothelial Growth Factor Expression in the Choke II Zone

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