The Effect of Activated Protein C on Attenuation of Ischemia-Reperfusion Injury in a Rat Muscle Flap Model

Zhang, Elizabeth W.; Fang, Taolin; Arnold, Peter; Songcharoen, Somjade J.; Lineaweaver, William C.; Zhang, Feng

doi:10.1097/sap.0000000000000118

Cited by 14 publications

(3 citation statements)

References 48 publications

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“…In orthopedics and plastic surgery, flap transplantation is a common method for repairing large-scale skin wounds (26,27). Factors affecting the quality of flap survival include arterial blood supply (28), venous return (29), tissue damage (30) and ischemia-reperfusion injury (31). Among these, ischemic injury is the key factor leading to flap necrosis following surgery (32).…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV improves angiogenesis under hypoxic conditions by enhancing hypoxia‑inducible factor‑1α SUMOylation

Wang

Chu

et al. 2021

Mol Med Rep

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Improving angiogenic capacity under hypoxic conditions is essential for improving the survival of skin grafts, as they often lack the necessary blood supply. The stable expression levels of hypoxia-inducible factor-1α (HIF-1α) in the nucleus directly affect the downstream vascular endothelial growth factor (VEGF) signaling pathway and regulate angiogenesis in a hypoxic environment. Astragaloside IV (AS-IV), an active component isolated from Astragalus membranaceus , has multiple biological effects including antioxidant and anti-diabetic effects, and the ability to provide protection from cardiovascular damage. However, the mechanisms underlying these effects have not previously been elucidated. The present study investigated whether AS-IV promotes angiogenesis via affecting the balance between ubiquitination and small ubiquitin-related modifier (SUMO) modification of HIF-1α. The results demonstrated that persistent hypoxia induces changes in expression levels of HIF-1α protein and significantly increases the proportion of dysplastic blood vessels. Further western blotting experiments showed that rapid attenuation and delayed compensation of SUMO1 activity is one of the reasons for the initial increase then decrease in HIF-1α levels. SUMO1 overexpression stabilized the presence of HIF-1α in the nucleus and decreased the extent of abnormal blood vessel morphology observed following hypoxia. AS-IV induces vascular endothelial cells to continuously produce SUMO1, stabilizes the HIF-1α/VEGF pathway and improves angiogenesis in hypoxic conditions. In summary, the present study confirmed that AS-IV stimulates vascular endothelial cells to continuously resupply SUMO1, stabilizes the presence of HIF-1α protein and improves angiogenesis in adverse hypoxic conditions, which may improve the success rate of flap graft surgery following trauma or burn.

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Section: Discussionmentioning

confidence: 99%

Astragaloside IV improves angiogenesis under hypoxic conditions by enhancing hypoxia‑inducible factor‑1α SUMOylation

Wang

Chu

et al. 2021

Mol Med Rep

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“…Given its dynamic property, the innervated gracilis muscle is used extensively to restore various muscle deficiencies and chronic muscle denervation. 20 , 21 Thus, unlike the autologous cartilage graft, the gracilis muscle can change its volume voluntarily and directionally. When the penile erection is initiated, the influx of blood into the corporal spaces is triggered and the length and stiffness of the penile shaft increase significantly.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Penile Corpora Cavernosa Reconstruction Using Bilateral Innervated Gracilis Muscles: A Preclinical Investigation

et al. 2018

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IntroductionProsthesis-assisted penile reconstruction has been performed extensively to restore a cosmetically acceptable phallus. However, a large number of patients will undergo revision surgery for various prosthesis-related complications.AimTo develop a 1-stage prosthesis-free dynamic cavernosa reconstruction method using bilateral innervated gracilis muscles and to investigate the feasibility and reliability of the surgical design.Methods10 fresh cadavers were dissected to assess the availability of bilateral gracilis muscles for functional cavernosa rebuilding. 11 mongrel female dogs were involved in the penile reconstruction surgery. The neophallus consisted of bilateral gracilis muscles as the neo-cavernosa, a right gracilis skin flap as the neourethra, and a lower abdominal flap with an anterior rectus sheath as the skin envelope and neo-tunica albuginea. The function and structure of the neo-phalli were assessed 7 months postoperatively.Main Outcome MeasuresThe neurovascular pedicle length of the gracilis muscles and the volume of the gracilis venter musculi were measured in the cadaveric investigation. The average dimensions of the canine neo-phalli at rest and during electrostimulated erection were obtained and the muscular fatigue-resistant curve was drawn. Histologic evaluations also were performed.ResultsThe neurovascular pedicle length and volume of the gracilis muscles were sufficient to yield a nearly normal appearance of the neo-cavernosa in the cadaveric and animal studies. The muscular fatigue-resistant curve demonstrated adequate length, stiffness, and duration of erection of the neo-phalli to accomplish normal coitus. Histologic evaluations showed an intact neourethra and nearly normal muscle structure in the inner layer of the canine neo-cavernosa, except for significantly increased amount of collagen fibers and type I/III collagen ratio in the outer layer of the neo-cavernosa. The percentage of type II (fatigue-prone) muscle fibers did not change significantly.ConclusionOur preclinical investigation proves that corpora cavernosa reconstruction using bilateral innervated gracilis muscles is technically feasible and functionally efficacious.Yin Z, Liu L, Xue B, et al. Dynamic Penile Corpora Cavernosa Reconstruction Using Bilateral Innervated Gracilis Muscles: A Preclinical Investigation. Sex Med 2018;6:162–170.

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“…The severance of blood supply from neighboring angiosomes during surgery induces ischemia and ischemic tissue damage 4 , 5 , which triggers inflammation, but also, as a compensatory response, angiogenesis and vascular collateralization from the principle artery, called arteriogenesis 3 , 6 . Arteriogenesis occurs through the primary remodeling of small, preexisting arteries into large conductance vessels capable of maintaining or restoring perfusion 7 .…”

Section: Introductionmentioning

confidence: 99%

A new fasciocutaneous flap model identifies a critical role for endothelial Notch signaling in wound healing and flap survival

Dastagir

Gamrekelashvili

Dastagir

et al. 2023

Sci Rep

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Flap surgery is a common treatment for severe wounds and a major determinant of surgical outcome. Flap survival and healing depends on adaptation of the local flap vasculature. Using a novel and defined model of fasciocutaneous flap surgery, we demonstrate that the Notch ligand Delta-like 1 (Dll1), expressed in vascular endothelial cells, regulates flap arteriogenesis, inflammation and flap survival. Utilizing the stereotyped anatomy of dorsal skin arteries, ligation of the major vascular pedicle induced strong collateral vessel development by end-to-end anastomosis in wildtype mice, which supported flap perfusion recovery over time. In mice with heterozygous deletion of Dll1, collateral vessel formation was strongly impaired, resulting in aberrant vascularization and subsequent necrosis of the tissue. Furthermore, Dll1 deficient mice showed severe inflammation in the flap dominated by monocytes and macrophages. This process is controlled by endothelial Dll1 in vivo, since the results were recapitulated in mice with endothelial-specific deletion of Dll1. Thus, our model provides a platform to study vascular adaptation to flap surgery and molecular and cellular regulators influencing flap healing and survival.

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The Effect of Activated Protein C on Attenuation of Ischemia-Reperfusion Injury in a Rat Muscle Flap Model

Cited by 14 publications

References 48 publications

Astragaloside IV improves angiogenesis under hypoxic conditions by enhancing hypoxia‑inducible factor‑1α SUMOylation

Astragaloside IV improves angiogenesis under hypoxic conditions by enhancing hypoxia‑inducible factor‑1α SUMOylation

Dynamic Penile Corpora Cavernosa Reconstruction Using Bilateral Innervated Gracilis Muscles: A Preclinical Investigation

A new fasciocutaneous flap model identifies a critical role for endothelial Notch signaling in wound healing and flap survival

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