Ex-vivo perfusion as a successful strategy for reduction of ischemia-reperfusion injury in prolonged muscle flap preservation – A gene expression study

Kruit, Anne Sophie; Smits, Laura; Pouwels, A.J.E.M.; Schreinemachers, Marie-Claire J.M.; Hummelink, Stefan; Ulrich, Dietmar

doi:10.1016/j.gene.2019.03.021

Cited by 17 publications

(13 citation statements)

References 47 publications

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“…A bladder catheter was inserted and continuous arterial blood pressure monitoring was possible through a femoral artery line. This experiment followed a mid‐thermic perfusion protocol and used a commercially available acellular solution (University of Wisconsin machine perfusion solution; UW‐mp), based on positive results in previous experiments with musculocutaneous flap replantation [18,19]. Primary outcomes were muscle contraction upon nerve stimulation and muscle histology.…”

Section: Methodsmentioning

confidence: 99%

Successful 18‐h acellular extracorporeal perfusion and replantation of porcine limbs ‐ Histology versus nerve stimulation

et al. 2021

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Summary The current standard for composite tissue preservation is static cold storage (SCS) and is limited to 6 h until irreversible muscle damage occurs. Extracorporeal perfusion (ECP) is a promising technique for prolonged preservation, however, functional results have been scarcely researched. This article assessed neuromuscular function and compared results to histological alterations to predict muscle damage after ECP. Forelimbs of twelve Dutch landrace pigs were amputated and preserved by 4 h SCS at 4–6 °C (n = 6) or 18 h mid‐thermic ECP with University of Wisconsin solution (n = 6). Limbs were replanted and observed for 12 h. Sham surgery was performed on contralateral forelimbs (n = 12). Histology analysis scored four subgroups representing different alterations (higher score equals more damage). Muscle contraction after median nerve stimulation was comparable between ECP, SCS, and sham limbs (P = 0.193). Histology scores were higher in ECP limbs compared to SCS limbs (4.8 vs. 1.5, P = 0.013). This was mainly based on more oedema in these limbs. In‐vivo muscle contraction was well preserved after 18 h ECP compared to short SCS, although histology seemed inferior in this group. Histology, therefore, did not correlate to muscle function at 12 h after replantation. This leads to the question whether histology or neuromuscular function is the best predictor for transplant success.

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Section: Methodsmentioning

confidence: 99%

Successful 18‐h acellular extracorporeal perfusion and replantation of porcine limbs ‐ Histology versus nerve stimulation

et al. 2021

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“…As this novel approach offers a successful preservation in SOT, recent studies have explored its putative benefit in VCA [13,14]. For instance, ex-vivo hypothermic oxygenated perfusion was shown to prolong preservation time in a porcine limb transplant model [15]; as well as to delay acute rejection and reduce proinflammatory/apoptotic gene expression profile in a porcine free-muscle flap model [16]. Of note, human limb transplant appeared viable for up to 24 h of normothermic ex-vivo perfusion [11].…”

Section: Key Pointsmentioning

confidence: 99%

Vascularized composite allotransplantation versus solid organ transplantation: innate-adaptive immune interphase

Kadono¹,

Gruszynski

Azari³

et al. 2019

Current Opinion in Organ Transplantation

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Purpose of reviewVascularized composite allotransplantation (VCA), a life-enhancing treatment for patients with complex tissue defects, trauma or illness, expounds upon the foundation of solid organ transplantation (SOT), the gold standard in end-stage organ failure. As innate and adaptive immunity remain the fundamental concern, this review highlights divergent immunobiology responses in VCA and SOT recipients. Recent findingsHost innate immune activation drives peritransplant tissue ischemia-reperfusion injury (IRI). Despite the direct relationship between ischemia-reperfusion (IR)-stress and cell-mediated acute rejection, the mechanism of how IRI may affect VCA loss needs investigation. With skin grafts being highly immunogenic, the incidence of cell-mediated rejection is higher in VCA than SOT; whereas ex-vivo perfusion may exert cytoprotection against IRI in VCA and SOT. New treatment concepts, such as topical immunosuppression or cell-based tolerogenic therapies, may avoid systemic immunosuppression in VCA. Although antibody-mediated rejection is relatively rare in VCA and its disease seems to be distinct from that in SOT, little is known as to whether and how IRI may influence humoral immune rejection cascade in VCA or SOT.

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“…In the current study, it is hypothesised that prolonged ECP is also possible in free flaps consisting almost entirely of skeletal muscle. Skeletal muscle is an important tissue to preserve in composite grafts since it is highly ischemia-sensitive and accounts for graft function [5,15,16]. Based on clinical appearance and gene expression patterns in previous experiments that assessed 36 h of ECP in musculocutaneous flaps, the maximum period of 18 h ECP was chosen.…”

Section: Introductionmentioning

confidence: 99%

“…Based on clinical appearance and gene expression patterns in previous experiments that assessed 36 h of ECP in musculocutaneous flaps, the maximum period of 18 h ECP was chosen. Outcomes after prolonged ECP were compared to a negative control group, consisting of flaps preserved by 4 h SCS [15,16].…”

Section: Introductionmentioning

confidence: 99%

Rectus Abdominis Flap Replantation after 18 h Hypothermic Extracorporeal Perfusion—A Porcine Model

Kruit

Midden

Schreinemachers

et al. 2021

JCM

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Cold storage remains the clinical standard for composite tissue preservation but is time-limited. A long ischemia time during surgery will adversely affect postoperative outcomes due to ischemia-reperfusion injury. Extracorporeal perfusion (ECP) seems to be a promising alternative for prolonged preservation, but more evidence is needed to support its use and to identify optimal perfusion fluids. This article assessed musculocutaneous flap vitality after prolonged ECP and compared outcomes after replantation to short static cold storage (SCS). Unilateral musculocutaneous rectus abdominis flaps were raised from 15 pigs and preserved by 4 h SCS (n = 5), 18 h mid-thermic ECP with Histidine–Tryptophan–Ketoglutarate (HTK, n = 5) or University of Wisconsin solution (UW, n = 5). Flaps were replanted and observed for 12 h. Skeletal muscle histology was assessed (score 0–12; high scores equal more damage), blood and perfusate samples were collected and weight was recorded as a marker for oedema. Mean histological scores were 4.0 after HTK preservation, 5.6 after UW perfusion and 5.0 after SCS (p = 0.366). Creatinine kinase (CK) was higher after ECP compared to SCS (p < 0.001). No weight increase was observed during UW perfusion, but increased 56% during HTK perfusion. Following 12 h reperfusion, mean weight gain reduced 39% in the HTK group and increased 24% in the UW group and 17% in the SCS group. To conclude, skeletal muscle seemed well preserved after 18 h ECP with HTK or UW perfusion, with comparable histological results to 4 h SCS upon short reperfusion. The high oedema rate during HTK perfusion remains a challenge that needs to be further addressed.

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Ex-vivo perfusion as a successful strategy for reduction of ischemia-reperfusion injury in prolonged muscle flap preservation – A gene expression study

Cited by 17 publications

References 47 publications

Successful 18‐h acellular extracorporeal perfusion and replantation of porcine limbs ‐ Histology versus nerve stimulation

Successful 18‐h acellular extracorporeal perfusion and replantation of porcine limbs ‐ Histology versus nerve stimulation

Vascularized composite allotransplantation versus solid organ transplantation: innate-adaptive immune interphase

Rectus Abdominis Flap Replantation after 18 h Hypothermic Extracorporeal Perfusion—A Porcine Model

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