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warm ischemia injury and reperfusion

Ulrich Keppler, Mohammed R Moussavian, Pascal Jeanmonod, Moritz J Strowitzki, Mathias Wagner, Claudia Scheuer, Michael D Menger, Maximilian von Heesen
BACKGROUND Ischemic type biliary lesions (ITBL) is a troublesome complication after liver transplantation. Little is known about its pathogenesis and there is particularly little data about morphological alterations. Prolonged warm and cold ischemia time and reduced hepatic arterial perfusion are risk factors leading to ITBL. There are only a few animal models described in literature. Therefore, we examined the effects of 3 h of hepatic artery ischemia-reperfusion (3 h I/R) and hepatic arterial ligation (HAL), both combined with ligation of the peribiliary plexus (PBP)...
October 21, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Luca Villa, Roberta Buono, Mara Ferrandi, Isabella Molinari, Fabio Benigni, Arianna Bettiga, Giorgia Colciago, Masami Ikehata, Elisabetta Messaggio, Maria Pia Rastaldi, Francesco Montorsi, Andrea Salonia, Paolo Manunta
Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks...
October 14, 2016: International Journal of Molecular Sciences
Keiji Ohata, Toyofumi F Chen-Yoshikawa, Toshi Menju, Ei Miyamoto, Satona Tanaka, Mamoru Takahashi, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date
BACKGROUND: Rho-kinase, an intracellular serine/threonine kinase, is a key regulator of cytoskeletal dynamics. Recent studies have demonstrated that Rho-kinase is involved in the ischemia-reperfusion injury (IRI) pathogenesis of many organs; however, its involvement with lung IRI remains unclear. This study assessed the association of Rho-kinase with lung IRI and evaluated the protective effect of inhaled Rho-kinase inhibitors in lung IRI. METHODS: The study included isolated rat lung perfusion models, divided into three groups: sham, Rho-kinase inhibitor, and warm ischemia (n = 6 each)...
October 12, 2016: Annals of Thoracic Surgery
J Hunter Mehaffey, Eric J Charles, Ashish K Sharma, Dustin T Money, Yunge Zhao, Mark H Stoler, Christine L Lau, Curtis G Tribble, Victor E Laubach, Mark E Roeser, Irving L Kron
OBJECTIVE: Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. METHODS: Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation...
September 22, 2016: Journal of Thoracic and Cardiovascular Surgery
B Barrou, N Chatauret, T Hauet, R Thuret, F Kleinclauss, M-O Timsit, R Codas, X Matillon, L Badet
AIMS: To describe ischemia-reperfusion mechanisms, the impact on kidney graft and strategies developed to minimize ischemia-reperfusion damages. MATERIAL AND METHODS: An exhaustive systematic review of the scientific literature was performed in the Medline database ( and Embase ( using different associations of the following keywords: ischemia-reperfusion; organ preservation; hypothermic machine perfusion; renal transplantation...
September 29, 2016: Progrès en Urologie
Beatriz Prieto-Moure, José M Lloris-Carsí, Mariola Belda-Antolí, Luis H Toledo-Pereyra, Dolores Cejalvo-Lapeña
Allopurinol is a well-known antioxidant that protects tissue against ischemia and reperfusion injury, blocking purine catabolism, and possibly reducing TNF-α and other cytokines. It also plays a significant role in reducing the inflammatory processes by inhibiting chemotaxis and other inflammatory mediators. The objective of this study was to define the role of allopurinol regarding kidney ischemic injury particularly as to its effect on inflammatory molecules such as TNF-α, IL-1β, and IL-6 response. One hundred and twenty five rats were subjected to warm renal ischemia...
October 3, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Pierre-Olivier Delpech, Raphael Thuillier, Thibault SaintYves, Jerome Danion, Sylvain Le Pape, Edwin S van Amersfoort, Beatrijs Oortwijn, Gilles Blancho, Thierry Hauet
BACKGROUND: Ischemia reperfusion injury (IRI) induced immune response is a critical issue in transplantation. Complement and contact system activation are among its key mechanisms. STUDY DESIGN: We investigated the benefits of pre-reperfusion treatment with recombinant human C1INH (rhC1INH), inhibitor of both complement and contact activation, in a pig model of kidney autotransplantation, subjecting the organ to 60 min warm ischemia prior to 24 h static preservation to maximize damage...
2016: Journal of Translational Medicine
Desiree D Rosselli, Jennifer L Mumaw, Vanna Dickerson, Cathy A Brown, Scott A Brown, Chad W Schmiedt
OBJECTIVE: To evaluate the effects of allogeneic mesenchymal stem cells (MSCs) in a model of ischemic acute kidney injury (AKI). STUDY DESIGN: Randomized controlled trial. ANIMALS: Adult, purpose-bred research cats (n=15) and a historical reference group (n=3). METHODS: Cats underwent unilateral, in vivo, warm renal ischemia, then intravenous administration of 4 million adipose-derived MSCs, bone marrow-derived MSCs, or fibroblasts (n=5/treatment) 1h after reperfusion...
October 2016: Research in Veterinary Science
Toshihiko Sawada, Katsuhiko Inoue, Dairou Tanabe, Shunji Kawamoto, Tatsuya Tsuji, Seiki Tashiro
Purposes; FK506 (strong immunosuppressive agent) was investigated experimentally whether to protect the hepatic IRI. Methods; Warm ischemic experiment using pigs and rats were performed and examined whether FK506 is effective. Results; The results obtained are as follows. 1. Warm ischemia allowed time of the pigs without FK506 was 150 minutes, but as for that of FK506 group, the extension of 30 minutes was got in 180 minutes. 2. Biliary excretion rate of BSP after reperfusion were better in the group of 180 minutes ischemia with FK506 than in without FK506 group...
2016: Journal of Medical Investigation: JMI
Haojun Yang, Haoming Zhou, Lin Zhuang, Xuehao Wang, Ling Lv
BACKGROUND: The G protein-coupled receptor TGR5 is a novel plasma membrane-bound G protein-coupled bile acid (BA) receptor. TGR5-induced liver protection has been demonstrated during several liver diseases, except during ischemia/reperfusion injury (IRI). METHOD: Male adult wild-type and TGR5 knockout mice were subjected to liver partial warm ischemia/reperfusion. Hepatic injury was evaluated based on serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST)...
September 6, 2016: Liver Transplantation
Kate Nong, Weiwei Wang, Xin Niu, Bin Hu, Chenchao Ma, Yueqing Bai, Bo Wu, Yang Wang, Kaixing Ai
BACKGROUND: This study aimed to evaluate the effect of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo) on hepatic ischemia-reperfusion (I/R) injury. METHODS: Exosomes were isolated and concentrated from conditioned medium using ultracentrifugation and ultrafiltration. hiPSC-MSCs-Exo were injected systemically via the inferior vena cava in a rat model of 70% warm hepatic I/R injury, and the therapeutic effect was evaluated...
August 31, 2016: Cytotherapy
Alireza Raissadati, Raimo Tuuminen, Alexey Dashkevich, Maija Bry, Riikka Kivelä, Andrey Anisimov, Simo Syrjälä, Ralica Arnaudova, Eeva Rouvinen, Mikko Ai Keränen, Rainer Krebs, Antti I Nykänen, Karl B Lemström
OBJECTIVES: Cardiac vascular endothelial growth factor-B transgene limits myocardial damage in rat infarction models. We investigated whether heart transplant vascular endothelial growth factor-B overexpression protected against ischemia-reperfusion injury. MATERIALS AND METHODS: We transplanted hearts heterotopically from Dark Agouti to Wistar Furth rats. To characterize the role of vascular endothelial growth factor-B in ischemia-reperfusion injury, we transplanted either long-term human vascular endothelial growth factor-B transgene overexpressing hearts from Wistar Furth rats or short-term adeno-associated virus 9-human vascular endothelial growth factor-B-transduced hearts from Dark Agouti rats into Wistar Furth rats...
September 1, 2016: Experimental and Clinical Transplantation
Kelvin Henrique Vilalva, Fabrícia Teixeira Mumic, Marina Rodrigues Garcia Silveira, Enio David Mente, Paulo Roberto Barbosa Evora, Orlando Castro E Silva
A 57-year-old female patient received elective liver transplant due to nonalcoholic steatohepatitis complicated by hepatocellular carcinoma. Her preoperative Model for End-Stage Liver Disease score was 11. The total transplant ischemic time was 10 hours and 35 minutes, and the warm ischemic time was 35 minutes. Even with aggressive fluid overload and use of high concentrations of vasoactive amines, the patient developed possible primary graft dysfunction with poor response to fluids and vasopressor support, suggesting vasoplegic syndrome...
August 24, 2016: Experimental and Clinical Transplantation
Sergi Guixé-Muntet, Fernanda Cristina de Mesquita, Sergi Vila, Virginia Hernández-Gea, Carmen Peralta, Juan Carlos García-Pagán, Jaime Bosch, Jordi Gracia-Sancho
BACKGROUND & AIMS: The transcription factor Krüppel-like factor 2 (KLF2), inducible by simvastatin, confers endothelial vasoprotection. Considering recent data suggesting activation of autophagy by statins, we aimed to: 1) characterize the relationship between autophagy and KLF2 in the endothelium, 2) assess this relationship in acute liver injury (cold ischemia/reperfusion) and 3) study the effects of modulating KLF2-autophagy in vitro and in vivo. METHODS: Autophagic flux, the vasoprotective KLF2 pathway, cell viability and microvascular function were assessed in endothelial cells and in various pre-clinical models of acute liver injury (cold storage and warm reperfusion)...
August 18, 2016: Journal of Hepatology
H Mrazkova, R Lischke, J Herget
As with other organ transplants even lung transplantation raises the question of the possibility of the influence of gender on ischemia-reperfusion injury. This is a current topic especially for increasingly utilized method of lung transplantation from a non-heart-beating donors, where reperfusion preceded by a period of warm and cold ischemia with subsequent treatment options for lung graft reperfusion. For measurements we used our laboratory previously created and validated animal model for ex vivo lung transplantation...
August 19, 2016: Physiological Research
Toshiaki Kashiwadate, Shigehito Miyagi, Yasuyuki Hara, Yorihiro Akamatsu, Satoshi Sekiguchi, Naoki Kawagishi, Noriaki Ohuchi, Susumu Satomi
Transplantation using grafts obtained after cardiac death (CD) is considered a promising solution for graft shortages. However, no standard criteria for organ preservation have been established for CD donors. High-mobility group box 1 (HMGB1) is a DNA-binding protein that is released from dying hepatocytes as an early mediator of inflammation and organ tissue damage. HMGB1 stimulates immunocytes to produce inflammatory cytokines, thereby amplifying the inflammatory response. Thrombomodulin is an integral membrane protein that functions as an endothelial anticoagulant cofactor, and it binds HMGB1 through the extracellular domain...
2016: Tohoku Journal of Experimental Medicine
An Martens, Marc Boada, Bart M Vanaudenaerde, Stijn E Verleden, Robin Vos, Geert M Verleden, Eric K Verbeken, Dirk Van Raemdonck, Dominique Schols, Sandra Claes, Arne P Neyrinck
Donation after circulatory death (DCD) is being used to increase the number of transplantable organs. The role and timing of steroids in DCD donation and ex-vivo lung perfusion (EVLP) has not been thoroughly investigated. In this study, we investigated the effect of steroids on warm-ischemic injury in a porcine model (n=6/group). Following cardiac arrest, grafts were left untouched in the donor (90 minutes warm ischemia). Graft function was assessed after 6 hours of EVLP. In MP-group, 500 mg methylprednisolone was given prior to cardiac arrest and during EVLP...
August 12, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Dietrich A Ruess, Moriz Probst, Goran Marjanovic, Uwe A Wittel, Ulrich T Hopt, Tobias Keck, Dirk Bausch
BACKGROUND: Histone deacetylases (HDAC) catalyze N-terminal deacetylation of lysine-residues on histones and multiple nuclear and cytoplasmic proteins. In various animal models, such as trauma/hemorrhagic shock, ischemic stroke or myocardial infarction, HDAC inhibitor (HDACi) application is cyto- and organoprotective and promotes survival. HDACi reduce stress signaling, cell death and inflammation. Hepatic ischemia-reperfusion (I/R) injury during major liver resection or transplantation increases morbidity and mortality...
2016: PloS One
Asma Mahfoudh Boussaid, Rabi Selmi, Mohamed Bejaoui, Kaouther Hadj Ayed, Mohamed Amine Zaouali, Hassen Ben Abdennebi
BACKGROUND/AIM: The aim of this study was to compare the effects of single and repeated trimetazidine (TMZ) administration against warm hepatic ischemia/reperfusion (I/R) injury and to explore the possible mechanisms affected by TMZ. MATERIALS AND METHODS: Wistar rats were divided into 4 groups (n = 6). Sham: rats were subjected to dissection. I/R: rats were subjected to 60 min of partial hepatic ischemia followed by 24 h of reperfusion. TMZ1: Same as I/R group but rats were pretreated with a single dose of TMZ (10 mg/kg, intraperitoneal injection) 30 min before warm ischemia...
2016: Turkish Journal of Medical Sciences
Solenne Tillet, Sébastien Giraud, Thomas Kerforne, Thibaut Saint-Yves, Sandrine Joffrion, Jean-Michel Goujon, Jerôme Cau, Gérard Mauco, Maurice Petitou, Thierry Hauet
Coagulation is an important pathway in the pathophysiology of ischemia-reperfusion injuries. In particular, deceased after circulatory death (DCD) donors undergo a no-flow period, a strong activator of coagulation. Hence, therapies influencing the coagulation cascade must be developed. We evaluated the effect of a new highly specific and effective anti-Xa/IIa molecule, with an integrated innovative antidote site (EP217609), in a porcine preclinical model mimicking injuries observed in DCD donor kidney transplantation...
July 25, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
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