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warm ischemia injury and reperfusion

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
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
Raven Henderson, Debra A Reilly, Jeffrey S Cooper
Natural and synthetic fillers have revolutionized aesthetic facial rejuvenation and soft-tissue augmentation. We present a case highlighting the dangers of filler self-injection. A 37-year-old woman self-injected a dermal filler around both temples. She immediately experienced left--side hearing loss, blanching over the left face, and pain. Prompt treatment with hyaluronidase, topical nitro paste, and warm compresses ensued. An emergency computed tomography angiogram showed occlusion of a superficial temporal artery branch...
January 2018: Plastic and Reconstructive Surgery. Global Open
Haoming Zhou, Han Wang, Ming Ni, Shi Yue, Yongxiang Xia, Ronald W Busuttil, Jerzy W Kupiec-Weglinski, Ling Lu, Xuehao Wang, Yuan Zhai
BACKGROUND & AIMS: Glycogen synthase kinase 3β (Gsk3β) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischemia and reperfusion injuries (IRI) have been well documented, underlying mechanisms remain ambiguous, due in part to the lack of cell-specific tools in vivo. METHODS: We created a myeloid-specific Gsk3β KO strain to study its function in macrophages in a murine liver partial warm ischemia model...
February 13, 2018: Journal of Hepatology
Pribadi Wiranda Busro, Harvey Romolo, Sudigdo Sastroasmoro, Jusuf Rachmat, Mohammad Sadikin, Anwar Santoso, Cindy Elfira Boom, Suhendro Suwarto, Ahmad Aulia Jusuf
Introduction Myocardial protection is vital to ensure successful open heart surgery. Cardioplegic solution is one method to achieve good myocardial protection. Inevitably, ischemia-reperfusion injury occurs with aortic crossclamping. Histidine-tryptophan-ketoglutarate solution is a frequently used cardioplegia for complex congenital heart surgery. We postulated that addition of terminal warm blood cardioplegia before removal of the aortic crossclamp might improve myocardial protection. Method A randomized controlled trial was conducted on 109 cyanotic patients aged, 1 to 5 years who underwent complex biventricular repair...
January 1, 2018: Asian Cardiovascular & Thoracic Annals
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
Zhao Lei, Meihong Deng, Zhongjie Yi, Qian Sun, Richard A Shapiro, Hongbo Xu, Tunliang Li, Patricia A Loughran, John E Griepentrog, Hai Huang, Melanie J Scott, Feizhou Huang, Timothy R Billiar
Liver ischemia/reperfusion (I/R) injury occurs through induction of oxidative stress and release of damage-associated molecular patterns (DAMPs), including cytosolic DNA released from dysfunctional mitochondria or from the nucleus. Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a cytosolic DNA sensor known to trigger stimulator of interferon genes (STING) and downstream type1 interferon (IFN-I) pathways, which are pivotal innate immune system responses to pathogen. However, little is known about the role of cGAS/STING in liver I/R injury...
February 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Yong Tang, Hongpeng Chu, Guojun Cao, Xiaolong Du, Xiaobo Min, Chidan Wan
Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170 μmol/kg body weight) after orthotopic autologous liver transplantation...
February 8, 2018: Molecular Immunology
R G Guseinov, S V Popov, A N Gorshkov, K V Sivak, A G Martov
AIM: To investigate experimentally ultrastructural and biochemical signs of acute injury to the renal parenchyma after warm renal ischemia of various duration and subsequent reperfusion. MATERIALS AND METHODS: The experiments were performed on 44 healthy conventional female rabbits of the "Chinchilla" breed weighted 2.6-2.7 kg, which were divided into four groups. In the first, control, group included pseudo-operated animals. In the remaining three groups, an experimental model of warm ischemia of renal tissue was created, followed by a 60-minute reperfusion...
December 2017: Urologii︠a︡
Mohammed Al-Saeedi, Niels Steinebrunner, Hassan Kudsi, Niels Halama, Carolin Mogler, Markus W Büchler, Peter H Krammer, Peter Schemmer, Martina Müller
Ischemia-reperfusion injury is a common pathological process in liver surgery and transplantation, and has considerable impact on the patient outcome and survival. Death receptors are important mediators of ischemia-reperfusion injury, notably the signaling pathways of the death receptor CD95 (Apo-1/Fas) and its corresponding ligand CD95L. This study investigates, for the first time, whether the inhibition of CD95L protects the liver against ischemia-reperfusion injury. Warm ischemia was induced in the median and left liver lobes of C57BL/6 mice for 45 min...
January 26, 2018: Cell Death & Disease
Andrea Ferrigno, Clarissa Berardo, Laura Giuseppina Di Pasqua, Veronica Siciliano, Plinio Richelmi, Ferdinando Nicoletti, Mariapia Vairetti
2-Methyl-6-(phenylethynyl)pyridine (MPEP), a negative allosteric modulator of the metabotropic glutamate receptor (mGluR) 5, protects hepatocytes from ischemic injury. In astrocytes and microglia, MPEP depletes ATP. These findings seem to be self-contradictory, since ATP depletion is a fundamental stressor in ischemia. This study attempted to reconstruct the mechanism of MPEP-mediated ATP depletion and the consequences of ATP depletion on protection against ischemic injury. We compared the effects of MPEP and other mGluR5 negative modulators on ATP concentration when measured in rat hepatocytes and acellular solutions...
January 23, 2018: International Journal of Molecular Sciences
Rui Miguel Martins, Anabela Pinto Rolo, João Soeiro Teodoro, Emanuel Furtado, Rui Caetano Oliveira, José Guilherme Tralhão, Carlos Marques Palmeira
Liver transplantation is a therapeutic regimen to treat patients with non-malignant end-stage liver diseases and malignant tumors of hepatic origin. The ischemia/reperfusion (I/R) injury in liver transplantation is associated with disruption of mitochondrial function in the hepatic parenchyma. Several studies have been conducted in animal models to identify pharmacological therapeutic strategies to minimize the injury induced by the cold/warm I/R in liver transplantation. Most of these studies were conducted in unrealistic conditions without the potential to be translated to clinical usage...
January 19, 2018: International Journal of Molecular Sciences
Grzegorz Wystrychowski, Wojciech Wystrychowski, Władysław Grzeszczak, Andrzej Więcek, Robert Król, Antoni Wystrychowski
Renal ischemia-reperfusion injury (IRI) induces local inflammation leading to kidney damage. Since pentoxifylline (PTX) and steroids have distinct immunomodulatory properties, we aimed to evaluate for the first time their combined use in IRI-induced acute kidney injury (AKI) and chronic kidney disease (CKD) in rats. In two experiments, PTX (100 mg/kg body weight subcutaneously) was administered 90 min prior to renal IRI or/and methylprednisolone (MP; 100 mg/kg body weight intramuscularly) was infused 60 min after reperfusion of a solitary kidney (AKI model: 45 min ischemia, 48 male Sprague-Dawley rats) or one kidney with excision of contralateral kidney 2 weeks later (CKD model: 90 min ischemia, 38 rats)...
January 11, 2018: International Journal of Molecular Sciences
Claire Delsuc, Alexandre Faure, Julien Berthiller, Didier Dorez, Xavier Matillon, Vannary Meas-Yedid, Bernard Floccard, Guillaume Marcotte, Vanessa Labeye, Maud Rabeyrin, Ricardo Codas, Cécile Chauvet, Philip Robinson, Emmanuel Morelon, Lionel Badet, William Hanf, Thomas Rimmelé
BACKGROUND: Kidney transplantation following uncontrolled donation after circulatory death (uDCD) presents a high risk of delayed graft function due to prolonged warm ischemia time. In order to minimise the effects of ischemia/reperfusion injury during warm ischemia, normothermic recirculation recently replaced in situ perfusion prior to implantation in several institutions. The aim of this study was to compare these preservation methods on kidney graft outcomes. METHODS: The primary endpoint was the one-year measured graft filtration rate (mGFR)...
January 8, 2018: BMC Nephrology
Yuta Kakizaki, Shigehito Miyagi, Kenji Shimizu, Koji Miyazawa, Wataru Nakanishi, Kazuaki Tokodai, Yasuyuki Hara, Chikashi Nakanishi, Michiaki Unno, Takashi Kamei, Masafumi Goto, Susumu Satomi
BACKGROUND: We previously reported that short oxygenated warm perfusion before cold storage (CS) had improved the graft viability of rat livers from donors after cardiac death (DCD). In this study, we investigated the effectiveness of short-term oxygenated subnormothermic perfusion for different durations after CS in a rat DCD model. METHODS: We used an isolated perfused rat liver system. In Study 1: the grafts were retrieved from Wistar rats 30min after cardiac arrest (thoracotomy), preserved in CS for 6h, and perfused with oxygenated subnormothermic (20-25°C) Krebs-Henseleit buffer for different durations (0, 15, 30, 60, and 90min groups; n=5 in each)...
January 5, 2018: Transplantation
Rim Jawad, Melroy D'souza, Lisa Arodin Selenius, Marita Wallenberg Lundgren, Olof Danielsson, Greg Nowak, Mikael Björnstedt, Bengt Isaksson
AIM: To study the effects of warm ischemia-reperfusion (I/R) injury on hepatic morphology at the ultrastructural level and to analyze the expression of the thioredoxin (TRX) and glutaredoxin (GRX) systems. METHODS: Eleven patients undergoing liver resection were subjected to portal triad clamping (PTC). Liver biopsies were collected at three time points; first prior to PTC (baseline), 20 min after PTC (post-ischemia) and 20 min after reperfusion (post-reperfusion)...
December 8, 2017: World Journal of Hepatology
Shintaro Hashimoto, Masaki Honda, Takayuki Takeichi, Masataka Sakisaka, Yasuko Narita, Daiki Yoshii, Keiichi Uto, Seisuke Sakamoto, Yukihiro Inomata
BACKGROUND: Neutrophils are known to be key players in innate immunity. Activated neutrophils induce local inflammation, which results in pathophysiologic changes during intestinal ischemia-reperfusion injury (IRI). However, most studies have been based on static assessments, and few have examined real-time intravital neutrophil recruitment. We herein report a method for imaging and evaluating dynamic changes in the neutrophil recruitment in intestinal IRI using two-photon laser scanning microscopy (TPLSM)...
January 15, 2018: Biochemical and Biophysical Research Communications
Eun Kyung Choi, Jongyoon Baek, Sangyoung Park, Suk Hwan Baek, Joon-Hyuk Choi, Chae Hoon Lee, Eon-Gi Sung, Daelim Jee
BACKGROUND: Hepatic innate immune cells are considered to play a central role in the early phase of hepatic ischemia reperfusion (IR) injury. Transfusion of old red blood cells (RBCs) is known to prime immune cells, and transfusion before IR may exacerbate liver injury because of the expected hyperresponsiveness of immune cells. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were divided into four groups: sham operation (Sham); hepatic IR only (IR Control); and two transfusion groups, preischemic (Pre-T) and postischemic (Post-T), in which allogeneic RBCs stored for 2 weeks were transfused before hepatic IR or after reperfusion, respectively...
February 2018: Journal of Surgical Research
Takahiro Ito, Naohisa Kuriyama, Hiroyuki Kato, Akitoshi Matsuda, Shugo Mizuno, Masanobu Usui, Hiroyuki Sakurai, Shuji Isaji
BACKGROUND: Functional and structural damages in sinusoidal endothelial cells (SECs) have a crucial role during hepatic ischemia-reperfusion injury (IRI). In regulating endothelial function, sphingosine-1-phosphate receptor 1 (S1PR1), which is a G protein-coupled receptor, has an important role. The present study aimed to clarify whether SEW2871, a selective S1PR1 agonist, can attenuate hepatic damage caused by hepatic IRI, focusing on SEC functions. METHODS: In vivo, using a 60-min partial-warm IRI model, mice were treated with SEW2871 or without it (with vehicle)...
February 2018: Journal of Surgical Research
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