Prolonged Cold Ischemic Time Results in Increased Acute Rejection in a Rat Allotransplantation Model

Bo, Xiaochen; Xia, Wei; Zhang, Jin; Liu, Bei; Guo, Shuzhong

doi:10.1016/j.jss.2010.08.012

Cited by 16 publications

(12 citation statements)

References 31 publications

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“…There is strong evidence that IRI, an unavoidable complication in the process of Tx, can strongly impact graft quality 15 , augment graft allogenicity 8 , and strengthen the subsequent adaptive immune reaction 6–8 . In this study, we first demonstrated that complement plays an important role in IRI to VC allografts.…”

Section: Discussionmentioning

confidence: 99%

“…However, our knowledge on the influence of IRI in graft rejection has been gained in studies on solid organ Tx, and it has been proposed that composite tissue allografts are more susceptible to IRI than solid organs because of the heterogenous tissue types that all exhibit different immunogenicity 5 . Little is known about how IRI modulates longer-term outcomes after VCA, but increased ischemia times are associated with more frequent and more severe acute rejections with increased anti-donor lymphocyte proliferation following VCA 6–8 . Although acute rejection episodes can usually be successfully controlled, the number and severity of these episodes are associated with chronic rejection.…”

Section: Introductionmentioning

confidence: 99%

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Targeted Complement Inhibition Protects Vascularized Composite Allografts From Acute Graft Injury and Prolongs Graft Survival When Combined With Subtherapeutic Cyclosporine A Therapy

et al. 2017

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Background Recipients of vascularized composite allografts require aggressive and life-long immunosuppression, and since the surgery is usually performed in nonlife threatening situations, the development of strategies to minimize immunosuppression is especially pertinent for this procedure. We investigated how complement affects acute graft injury, alloimmunity, and immunosuppressive therapy. Methods Vascularized composite allografts were transplanted from Balb/C to C57BL/6 mice that were complement deficient (C3 or double C3a Receptor (R)/C5aR), or treated with a targeted complement inhibitor (CR2-Crry). Allografts were analyzed for acute inflammation and injury, subacute T cell response, and survival in the absence and presence of CsA therapy. Results Allografts in C3-deficient or CR2-Crry treated recipients were protected from skin and muscle ischemia reperfusion injury (IRI). C3aR/C5aR deficient recipients were more modestly protected. IgM and C3d colocalized within allografts from wild type and C3aR/C5aR-deficient recipients indicating IgM-mediated complement activation, and C3d deposition was almost absent in allografts from C3-deficient and CR2-Crry treated recipients. Inflammatory cell infiltration and P-selectin expression was also significantly reduced in C3-deficient and CR2-Crry treated recipients. Acute treatment with CR2-Crry or with 3 mg/kg/day cyclosporine A (CsA) modestly, but significantly increased median allograft survival from 5.8 to 7.4 and 7.2 days, respectively. However, combined acute CR2-Crry treatment and CsA therapy increased mean graft survival to 17.2 days. Protection was associated with significantly reduced T cell infiltration of allografts and Tc1 cells in recipient spleens. Conclusions Complement-mediated IRI augments graft allogenicity, and appropriate complement inhibition ameliorates IRI, decreases alloimmune priming and allows more immune-sparing CsA dosing.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeted Complement Inhibition Protects Vascularized Composite Allografts From Acute Graft Injury and Prolongs Graft Survival When Combined With Subtherapeutic Cyclosporine A Therapy

et al. 2017

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“…A histological analysis of biopsies in flaps with brief or prolonged ischemia (24 h) revealed no difference in the early onset of acute rejections, but demonstrated an accelerated inflammation in grafts with a prolonged ischemia. [69] Other experiments have also shown that prolonged ischemia in models of VCA-augmented adaptive immunity and increased rates of acute rejections. [70] Tolerable clinical ischemic times are currently not defined and clinical practice has aimed for brief periods of ischemia.…”

Section: Vascularized Composite Tissue Allotransplantation (Vca) — Rementioning

confidence: 99%

Current status of vascularized composite tissue allotransplantation

Edtinger¹,

Yang²,

Uehara³

et al. 2014

Burn Trauma

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Vascularized composite tissue allotransplantation (VCA) offers treatment options of complex functional deficiencies that cannot be repaired with conventional reconstructive methods. VCAs consist of blocks of functional units comprising different tissue types such as skin, bone, muscle, nerves, blood vessels, tendons, ligaments and others, and are thus substantially different from the composition of organ transplants. The field of VCA has made fascinating progresses in the recent past. Among other VCAs, numerous successful hand, face and limb transplants have been performed in the world. At the same time, specific questions in regard to innate and adaptive immunity, consequences of ischemia/reperfusion injury, immunosuppression, preservation, and regenerative capacity remain. In spite of this, the field is poised to make significant advances in the near future.

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“…Одной из актуальных проблем в трансплантологии остается ишемически-реперфузионное повреждение (ИРП) трансплантата, приводящее к развитию осложнений в раннем послеоперационном периоде [1]. Методом, способным ликвидировать любые формы кислородной задолженности, признана гипербарическая оксигенация (ГБО), которая осуществляет доставку кислорода к органам и тканям за счет растворения его в жидких средах организма [2,3].…”

Section: Introductionunclassified

Hyperbaric oxygenation in transplantology

Левина¹,

Евсеев²,

Хубутия³

et al. 2020

Transplantologiâ (Mosk.)

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The ability to eliminate any form of oxygen debt by transporting oxygen to organs and tissues, by dissolving it in body fluids, brings hyperbaric oxygenation to a new level of application in transplantology. The review discusses the pathophysiological aspects of hyperbaric oxygenation during ischemia and reinfusion, especially when used in transplantology, and also investigations on the use of hyperbaric oxygenation in model experiments and in clinical practice. Analysis of the efficacy of hyperbaric oxygenation therapy at various stages of the transplantation process (preconditioning, donation, organ storage, in the early and late post-transplant periods) allows us to conclude that this method should be more widely involved in transplantation practice.Authors declare no conflict of interest.

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Prolonged Cold Ischemic Time Results in Increased Acute Rejection in a Rat Allotransplantation Model

Cited by 16 publications

References 31 publications

Targeted Complement Inhibition Protects Vascularized Composite Allografts From Acute Graft Injury and Prolongs Graft Survival When Combined With Subtherapeutic Cyclosporine A Therapy

Targeted Complement Inhibition Protects Vascularized Composite Allografts From Acute Graft Injury and Prolongs Graft Survival When Combined With Subtherapeutic Cyclosporine A Therapy

Current status of vascularized composite tissue allotransplantation

Hyperbaric oxygenation in transplantology

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