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Transplantation,ischemia reperfusion injury

Danh T Tran, Scott Esckilsen, Jennifer Mulligan, Shikhar Mehrotra, Carl Atkinson, Satish N Nadig
BACKGROUND: Microvascular endothelial cells (ECs) are central to an allograft's immunogenicity. Cold ischemia and reperfusion injury associated with static cold storage and warm reperfusion activates ECs and increases the immunogenicity of the allograft. Following reperfusion, mitochondrial permeability transition pore (mPTP) opening contributes to mitochondrial dysfunction in the allograft, which correlates to alloimmune rejection. Current understanding of this relationship, however, centers on the whole allograft instead of ECs...
March 10, 2018: Transplantation
Francesca Maione, Nicholas Gilbo, Silvia Lazzaro, Peter Friend, Giovanni Camussi, Renato Romagnoli, Jacques Pirenne, Ina Jochmans, Diethard Monbaliu
BACKGROUND: Understanding ischemia reperfusion injury (IRI) is essential to further improve outcomes after liver transplantation (LT). Porcine isolated liver perfusion (ILP) is increasingly used to reproduce LT-associated IRI in a strictly controlled environment. However, whether ILP is a reliable substitute of LT was never validated. METHODS: We systematically reviewed the current experimental set-ups for ILP and parameters of interest reflecting IRI. RESULTS: ILP was never compared to transplantation in animals...
March 5, 2018: Transplantation
Felix C F Schmitt, Eduardo Salgado, Janina Friebe, Thomas Schmoch, Florian Uhle, Thomas Fleming, Johanna Zemva, Lars Kihm, Christian Nusshag, Christian Morath, Martin Zeier, Thomas Bruckner, Arianeb Mehrabi, Peter P Nawroth, Markus A Weigand, Stefan Hofer, Thorsten Brenner
BACKGROUND: A prolonged cold ischemia time (CIT) is suspected to be associated with an increased ischemia and reperfusion injury (IRI) resulting in an increased damage to the graft. METHODS: In total, 91 patients were evaluated for a delayed graft function within 7 days after kidney transplantation (48 deceased, 43 living donors). Blood and urine samples were collected before, immediately after the operation, and 1, 3, 5, 7 and 10 days later. Plasma and/or urine levels of total keratin 18 (total K18), caspase-cleaved keratin 18 (cc K18), the soluble receptor for advanced glycation end-products (sRAGE), tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein-7 ([TIMP-2]×[IGFBP7]) were measured...
March 5, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Zhuolun Song, Bostjan Humar, Anurag Gupta, Eleonora Maurizio, Nathalie Borgeaud, Rolf Graf, Pierre-Alain Clavien, Yinghua Tian
Defective regeneration of small-for-size (SFS) liver remnants and partial grafts remains a key limiting factor in the application of liver surgery and transplantation. Exogenous melatonin (MLT) has protective effects on hepatic ischemia reperfusion injury (IRI), but its influence on graft regeneration is unknown. The aim of the study is to investigate the role of MLT in IRI and graft regeneration in settings of partial liver transplantation. We established three mouse models to study hepatic IRI and regeneration associated with partial liver transplantation: (I) IR+PH group: 60 min liver ischemia (IR) plus 2/3 hepatectomy (PH); (II) IR+exPH group: 60 min liver IR plus extended hepatectomy (exPH) associated with the SFS syndrome; (III) SFS-LT group: Arterialized 30% SFS liver transplant...
March 5, 2018: Journal of Pineal Research
Qi Cheng, Kunal Patel, Biao Lei, Lindsay Rucker, D Patterson Allen, Peng Zhu, Chentha Vasu, Paulo N Martins, Martin Goddard, Satish N Nadig, Carl Atkinson
Donor brain death (BD) is an inherent part of lung transplantation (LTx) and a key contributor to ischemia-reperfusion injury (IRI). Complement activation occurs as a consequence of BD in other solid organ Tx and exacerbates IRI, but the role of complement in LTx has not been investigated. Here, we investigate the utility of delivering nebulized C3a receptor antagonist (C3aRA) pre-Transplant to BD donor lungs in order to reduce post-LTx IRI. BD was induced in Balb/c donors, and lungs nebulized with C3aRA or vehicle 30 minutes prior to lung procurement...
March 5, 2018: American Journal of Transplantation
Christopher W White, Simon J Messer, Stephen R Large, Jennifer Conway, Daniel H Kim, Demetrios J Kutsogiannis, Jayan Nagendran, Darren H Freed
Cardiac transplantation has become limited by a critical shortage of suitable organs from brain-dead donors. Reports describing the successful clinical transplantation of hearts donated after circulatory death (DCD) have recently emerged. Hearts from DCD donors suffer significant ischemic injury prior to organ procurement; therefore, the traditional approach to the transplantation of hearts from brain-dead donors is not applicable to the DCD context. Advances in our understanding of ischemic post-conditioning have facilitated the development of DCD heart resuscitation strategies that can be used to minimize ischemia-reperfusion injury at the time of organ procurement...
2018: Frontiers in Cardiovascular Medicine
Rui Miguel Martins, João Soeiro Teodoro, Emanuel Furtado, Anabela Pinto Rolo, Carlos Marques Palmeira, José Guilherme Tralhão
Ischemia/reperfusion (I/R) injury in liver transplantation can disrupt the normal activity of mitochondria in the hepatic parenchyma. This potential dysfunction of mitochondria after I/R injury could be responsible for the initial poor graft function or primary nonfunction observed after liver transplantation. Thus, determining the mechanisms that lead to human hepatic mitochondrial dysfunction might contribute to improving the outcome of liver transplantation. Furthermore, early identification of novel prognostic factors involved in I/R injury could serve as a key endpoint to predict the outcome of liver grafts and also to promote the early adoption of novel strategies that protect against I/R injury...
2018: International Journal of Medical Sciences
Fang Xie, Xiang Fei, Ming-Bo Zhang, Yan Zhang, Hong-Wei Wang, Jie Tang, Wen-Bo Tang, Yu-Kun Luo
The aim of this study was to evaluate microvascular perfusion after liver ischemia-reperfusion injury (IRI) in rabbits using the "flash-replenishment" method of contrast-enhanced ultrasound (CEUS) perfusion imaging. Twenty-eight rabbits underwent either 30, 60 or 90 min of ischemia and 120 min of reperfusion. CEUS perfusion imaging was performed using the "flash-replenishment" model, and hepatic microvascular perfusion parameters, including peak intensity (PI), area under the curve (AUC), and hepatic artery-to-vein transit time (HA-HVTT), were calculated...
February 22, 2018: Ultrasound in Medicine & Biology
Hester van Willigenburg, Peter L J de Keizer, Ron W F de Bruin
Kidney transplants from aged donors are more vulnerable to ischemic injury, suffer more from delayed graft function and have a lower graft survival compared to kidneys from younger donors. On a cellular level, aging results in an increase in cells that are in a permanent cell cycle arrest, termed senescence, which secrete a range of pro-inflammatory cytokines and growth factors. Consequently, these senescent cells negatively influence the local milieu by causing inflammaging, and by reducing the regenerative capacity of the kidney...
February 19, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Angela Hin, Caroline Kannengiesser, Arnaud Roussel, Benjamin Renaud-Picard, Antoine Roux, Martine Reynaud-Gaubert, Johanna Claustre, Adrien Tissot, Romain Guillemain, Jean-François Mornex, Sacha Mussot, Claire Dromer, Marcel Dahan, Olivier Brugière, Olaf Mercier, Raphaël Borie, Marina Pretolani, Yves Castier, Pierre Mordant
BACKGROUND: Club Cell Secretory Protein (CCSP) G38A polymorphism has recently been involved in lung epithelial susceptibility to external injuries. Lung transplantation (LT) is currently limited by ischemia-reperfusion injury leading to Primary Graft Dysfunction (PGD). We thus hypothesized that donor CCSP G38A polymorphism might impact the risk of PGD following LT. METHODS: We focused on LT included in the French multicentric Cohort in Lung Transplantation (COLT), performed between January 2009 and December 2014, and associated with preoperative blood samples from the donor and the recipient...
February 20, 2018: Transplantation
Ilker Iskender, Marcelo Cypel, Tereza Martinu, Manyin Chen, Jin Sakamoto, Hyunhee Kim, Keke Yu, Huiqing Lin, Zehong Guan, Kohei Hashimoto, Thomas K Waddell, Mingyao Liu, Shaf Keshavjee
BACKGROUND: Ischemia-reperfusion injury related to lung transplantation is a major contributor to early postoperative morbidity and mortality. We hypothesized that donation after cardiac death donor lungs experience warm ischemic conditions that activate different injurious mechanisms compared with donor lungs that undergo prolonged cold ischemic conditions. METHODS: Rat donor lungs were preserved under different cold ischemic times (CIT: 12 hours or 18 hours), or under warm ischemia time (WIT: 3 hours) after cardiac death, followed by single left lung transplantation...
February 20, 2018: Transplantation
Shoichi Kageyama, Kojiro Nakamura, Bibo Ke, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Liver ischemia-reperfusion injury (IRI) represents a risk factor for early graft dysfunction and an obstacle to expanding donor pool in orthotopic liver transplantation (OLT). We have reported on the crucial role of macrophage Notch1 signaling in mouse warm hepatic IRI model. However, its clinical relevance or therapeutic potential remain unknown. Here, we used Serelaxin (SER), to verify Notch1 induction and putative hepatoprotective function in IR-stressed OLT. C57BL/6 mouse livers subjected to extended (18hr) cold storage were transplanted to syngeneic recipients...
February 21, 2018: American Journal of Transplantation
Matheus Correa-Costa, David Gallo, Eva Csizmadia, Edward Gomperts, Judith-Lisa Lieberum, Carl J Hauser, Xingyue Ji, Binghe Wang, Niels Olsen Saraiva Câmara, Simon C Robson, Leo E Otterbein
Ischemia reperfusion injury (IRI) is the predominant tissue insult associated with organ transplantation. Treatment with carbon monoxide (CO) modulates the innate immune response associated with IRI and accelerates tissue recovery. The mechanism has been primarily descriptive and ascribed to the ability of CO to influence inflammation, cell death, and repair. In a model of bilateral kidney IRI in mice, we elucidate an intricate relationship between CO and purinergic signaling involving increased CD39 ectonucleotidase expression, decreased expression of Adora1, with concomitant increased expression of Adora2a/2b...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Songjie Cai, Naotsugu Ichimaru, Shiro Takahara
In deceased donors, ischemia/reperfusion injury (IRI) is an important cause of allograft dysfunction. Prolonged cold and warm ischemia time leads to a high risk of early post-transplant complications, including acute and chronic rejection. Ischemia not only up-regulates inflammatory cytokines and chemokines, but also enhances the expression of MHC-class II and adhesion molecules on epithelial and dendritic cells. Moreover, the danger associated molecular patterns (DAMPs) released from stressed or dying cells, not only cause or amplify tissue inflammation and trigger tissue repair in response to IRI, but also act as adjuvants that enhance DC maturation and potentiate the adaptive immune response...
February 13, 2018: Current Gene Therapy
Hailin Zhao, Han Huang, Azeem Alam, Qian Chen, Ka Chuen Suen, Jiang Cui, Qizhe Sun, Rele Ologunde, Wenwen Zhang, Qingquan Lian, Daqing Ma
Clinical evidence indicated a possible link between renal injury and remote liver injury. Herein, we investigated whether extracellular histone mediates remote hepatic damage following renal graft ischemia-reperfusion injury, whilst vascular endothelial growth factor (VEGF) is protective against remote hepatic injury. In vitro, hepatocyte HepG2 cultures were treated with histone. In vivo, the Brown-Norway renal graft was stored in 4°C preserving solution for 24 hours and then transplanted into Lewis rat recipient; blood samples and livers from recipients were harvested 24 hours after surgery...
February 15, 2018: American Journal of Transplantation
Jinyeol Kwon, Sung Mee Jung, Sae-Yeon Kim, Nyeong Keon Kwon, Sang-Jin Park
Vascularized composite allotransplantation for the forearm is a complex surgical procedure, requiring multidisciplinary collaboration. It is important to provide optimal blood flow to the grafts, effective immunosuppression, and early rehabilitation for graft survival and good functional outcomes. As ischemia-reperfusion injury and substantial but unquantifiable blood loss are inevitable in this type of surgery, anesthetic management should focus on providing adequate hemodynamic management with proper monitoring, and anesthetic and analgesic strategies to prevent vasoconstriction in the graft...
February 2018: Korean Journal of Anesthesiology
Yun Joo Park, Jang Won Lee, Yosep Chong, Tae Hwan Park
Identifying novel and safe immunosuppressants is of crucial importance. Recently, there have been several studies revealing that botulinum toxin A significantly alleviates ischemia-reperfusion injuries. Emerging evidence shows that ischemia-reperfusion injuries contribute to innate immune activation, promoting rejection and inhibiting tolerance. Therefore, we hypothesized that a pretreatment with botulinum toxin A might decrease allograft rejection in a rat transplantation model.Twenty-four Lewis rats were randomly assigned to two groups consisting of 12 rats each, depending on whether skin allograft was performed after pretreatment with botulinum toxin A  or with normal saline...
February 13, 2018: Bioscience Reports
Yingli Xie, Di Zhao, Pingshuan Dong, Lihong Lai
Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure. During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension...
February 12, 2018: Bioscience Reports
Xin Gan, Juan Li
Necrotizing enterocolitis (NEC) is a catastrophic disease caused by a variety of factors in neonates, especially preterm infants. Severe NEC has a high fatality rate, and most survivors may face short- and long-term adverse prognosis. Risk factors for NEC include preterm birth, non-breastfeeding, microbial abnormalities in the digestive tract, and ischemia-reperfusion injury. High-resolution abdominal ultrasound helps with the early diagnosis of NEC. The preventive measures for NEC include protecting the intestinal mucosa through nutritional intervention, interfering with intestinal injury signals, changing intestinal microflora, and performing early minimal enteral nutrition...
February 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Guodong Liu, Hongmei Zhang, Fengyun Hao, Jing Hao, Lixiao Pan, Qing Zhao, Jinshan Wo
BACKGROUND/AIMS: Ischemia-reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation and is a key factor in graft failure and the long-term survival rate of recipients. Therefore, there is an urgent need for the development of new therapies to prevent I/R injury. Clusterin is a hetero-dimeric glycoprotein with an antiapoptotic function. In this study, we investigated whether clusterin was cardioprotective in heart transplantation against I/R injury using an in vivo rat model and an in vitro cell culture system, and examined the underlying mechanisms of I/R injury...
February 5, 2018: Cellular Physiology and Biochemistry
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