|
1
|
|
|
2
|
Greca FH, Gonçalves NMFDM, Souza Filho ZAD, Noronha LD, Silva RFKCD, Rubin MR. The protective effect of methylene blue in lungs, small bowel and kidney after intestinal ischemia and reperfusion. Acta Cir Bras 2009; 23:149-56. [PMID: 18372960 DOI: 10.1590/s0102-86502008000200007] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2007] [Accepted: 12/21/2007] [Indexed: 11/21/2022] Open
Abstract
PURPOSE To study the role of methylene blue as an inhibitor of superoxide production by xanthine oxidase. METHODS Thirty-two Wistar rats were divided into 2 groups of 16 animals: the control group and the experimental group. All were submitted to a laparotomy for the occlusion of the cranial mesenteric artery during 60 minutes. The reperfusion was confirmed by the pulsation of the artery after the release of the temporary ligature and color change of the intestines. In the animals of the control group, 2 ml of saline were injected in the peritoneal cavity and in the animals of the experimental group, 2 ml of methylene blue were injected in the peritoneal cavity. After reperfusion for 4 hours, the animals were then sacrificed. The lungs were excised from all 32 rats. Simultaneously, the small intestine and kidneys were ressected in 20 animals (10 from the control group and 10 from the experimental group). Samples of the organs were taken to evaluate the action of xanthine-oxidase, for histopathology studies and for characterization of the edema. RESULTS In the animals of the experimental group, the inflammatory lesion as well as the edema in the lung was greater than in the control group. The intestinal and renal lesions were similar in both groups, but the lung damage was superior to that observed in the intestines and kidneys. . CONCLUSION Despite similar action of the xanthine oxidase in the control and the experimental group, after intestinal ischemia and reperfusion, the protective effect of methylene blue was observed only in the lungs of the experimental group.
Collapse
Affiliation(s)
- Fernando Hintz Greca
- Department of Experimental Surgery of the Pontifical Catholic University of Paraná, Brazil.
| | | | | | | | | | | |
Collapse
|
|
3
|
Vardanian AJ, Busuttil RW, Kupiec-Weglinski JW. Molecular mediators of liver ischemia and reperfusion injury: a brief review. Mol Med 2008; 14:337-45. [PMID: 18292799 DOI: 10.2119/2007-00134.vardanian] [Citation(s) in RCA: 122] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2007] [Accepted: 02/08/2008] [Indexed: 12/20/2022] Open
Abstract
Ischemia and reperfusion injury is a dynamic process that involves multiple organ systems in various clinical states including transplantation, trauma, and surgery. Research into this field has identified key molecular and signaling players that mediate, modulate, or augment cellular, tissue, and organ injury during this disease process. Further elucidation of the molecular mechanisms should provide the rationale to identify much-needed novel therapeutic options to prevent or ameliorate organ damage due to ischemia and reperfusion in clinics.
Collapse
Affiliation(s)
- Andrew J Vardanian
- The Dumont UCLA Transplantation Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, United States of America
| | | | | |
Collapse
|
|
4
|
Ma R, Sun JL, Zhang XQ, Dai Y, Sun JZ. Amelioration of Graft Ischmia-Reperfusion Injury by Breviscapine in Rat Small Bowel Transplantation. Transplant Proc 2006; 38:2788-90. [PMID: 17112830 DOI: 10.1016/j.transproceed.2006.08.182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2005] [Indexed: 11/30/2022]
Abstract
OBJECTIVE We sought to evaluate the effects of breviscapine to ameliorate graft ischemia-reperfusion (I/R) injury in a rat small bowel transplantation model. METHODS Thirty-six recipients were randomly divided into three groups (n = 12): operative controls, in which grafts were implanted immediately after harvesting; an I/R control group with grafts preserved in cold lactated Ringer's solution at 4 degrees C for 4 hours before transplantation; and a breviscapine group wherein the graft was treated in the same way as the I/R control group but breviscapine (25 mg/kg/d) was injected intraperitoneally into both the donors and the recipients for 3 days before the operation of and into the recipients after transplantation. We compared the pathological scores for I/R injury, apoptosis index, and content of malondialdehyde (MDA) in the graft. RESULTS Breviscapine diminished the pathological change caused by I/R injury (breviscapine vs I/R control on 24 hours after operation, 1.50 +/- 0.55 vs 2.17 +/- 0.75; P < .05), decreased the apoptotic index (breviscapine vs I/R control at 24 hours after operation, 27.33 +/- 0.167 vs 73.83 +/- 0.077; P < .05), and reduced the graft tissue content of MDA (breviscapine vs I/R control on 24 hours after operation, 1.717 +/- 0.131 vs 3.167 +/- 0.196; P < .05). CONCLUSIONS Breviscapine may protect the transplanted small intestine against I/R injury during transplantation in rats.
Collapse
Affiliation(s)
- R Ma
- Department of General Surgery, Qilu Hospital of Shandong University, Shandong, China
| | | | | | | | | |
Collapse
|
|
5
|
March S, Garcia-Pagán JC, Massaguer A, Pizcueta P, Panés J, Engel P, Bosch J. P-selectin mediates leukocyte rolling in concanavalin-A-induced hepatitis. Liver Int 2005; 25:1053-60. [PMID: 16162166 DOI: 10.1111/j.1478-3231.2005.01137.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
UNLABELLED Concanavalin-A (Con-A)-induced hepatitis is an experimental model of human autoimmune hepatitis characterized by leukocyte activation and infiltration of the liver. The aim of the present study was to evaluate the role of P-selectin on leukocyte-endothelial interactions within the hepatic microvasculature in response to Con-A. METHODS The study was performed in P-selectin-deficient mice and wild-type mice pretreated with anti-P-selectin blocking monoclonal antibody (mAb) or vehicle. After 2 h of Con-A (20 mg/kg i.v.) or PBS administration, leukocyte rolling and adhesion and the index of sinusoidal perfusion were evaluated using the intravital microscopy technique in the liver. Apoptosis was determined by flow cytometry analysis of caspase-3 activity assayed on freshly isolated hepatocytes. RESULTS Con-A induced a significant increase in leukocyte rolling, mainly located at the central venule (2.1+/-0.4 vs 0.6+/-0.2 cells/min in wild-type mice treated with vehicle) and less marked, but still significant, in portal venules. This was associated with a significant increase in leukocyte adhesion. In P-selectin-deficient mice treated with Con-A, leukocyte rolling in portal and central venules was markedly reduced. However, leukocyte adhesion was only partially attenuated. A few sinusoids were perfused in wild-type mice treated with Con-A (26%). The percentage of perfused sinusoids was significantly higher in P-selectin-deficient mice (45%; P<0.05 vs wild-type). Similar effects were noted after the simultaneous injection of Con-A and anti-P-selecting mAb in wild-type mice. After Con-A treatment, apoptosis was markedly reduced in isolated hepatocytes of P-selectin-deficent mice (37+/-7% vs 75+/-5% in wild type). CONCLUSION The results of this intravital microscopy study clearly demonstrate that P-selectin is involved in the initial leukocyte rolling that leads to the development of Con-A-induced liver injury.
Collapse
Affiliation(s)
- Sandra March
- Immunology Unit, Department of Cellular Biology and Pathology, Medical School, University of Barcelona, Villaroel 170, Barcelona, Spain
| | | | | | | | | | | | | |
Collapse
|
|
6
|
Stefanutti G, Lister P, Smith VV, Peters MJ, Klein NJ, Pierro A, Eaton S. P-selectin expression, neutrophil infiltration, and histologic injury in neonates with necrotizing enterocolitis. J Pediatr Surg 2005; 40:942-7; discussion 947-8. [PMID: 15991175 DOI: 10.1016/j.jpedsurg.2005.03.027] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND/PURPOSE P-selectin promotes adherence of leukocytes to the endothelium in inflammatory processes. The aim of this study was to investigate the expression of P-selectin and its role in the development of inflammation in neonates with necrotizing enterocolitis (NEC). METHODS Twenty-nine intestinal specimens from 13 neonates with NEC and 7 control neonates with congenital gastrointestinal abnormalities were studied. Histologic damage, immunohistochemical expression of P-selectin, and polymorphonuclear cell infiltrate were graded blindly. Mann-Whitney U and Spearman rank tests were used to compare grades. RESULTS Expression of P-selectin was increased in NEC compared with controls in both medium-sized vessels (P = .03) and in the microcirculation (P = .03). P-selectin expression on medium-sized vessels correlated with the degree of histologic injury (P = .02, r = 0.425). P-selectin expression was greatest in areas of active inflammation but markedly lower in necrotic areas. The degree of polymorphonuclear cell infiltration strongly correlated with P-selectin expression on both medium-sized vessels (P = .004, r = 0.513) and the microcirculation (P = .001, r = 0.578). CONCLUSIONS Expression of P-selectin is increased in medium-sized vessels and in the microcirculation in intestinal specimens of neonates with NEC compared with neonatal controls. Expression of P-selectin is associated with the recruitment of polymorphonuclear cells and the severity of histologic injury, although P-selectin expression is lost in necrotic tissue.
Collapse
Affiliation(s)
- Giorgio Stefanutti
- Department of Paediatric Surgery, Institute of Child Health and Great Ormond Street Hospital, WC1N 1EH London, UK
| | | | | | | | | | | | | |
Collapse
|
|
7
|
Wang SF, Liang Q, Li GW, Gao K. Gene expression profile in rat small intestinal allografts after cold preservation/reperfusion. World J Gastroenterol 2005; 11:885-9. [PMID: 15682487 PMCID: PMC4250603 DOI: 10.3748/wjg.v11.i6.885] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the changes of gene expression profile in small intestinal allografts in rats after cold preservation/reperfusion, and to identify the genes relevant to cold preservation/reperfusion injury.
METHODS: Heterotopic segmental small bowel transpla-ntation was performed in six rats with a sham operation and they were used as controls. Total RNA was extracted from the allografts (experimental group) and normal intestines (control group) 1 h after cold preservation/reperfusion, and then purified to mRNA, which was then reversely transcribed to cDNA, and labeled with fluorescent Cy5-dUTP and Cy3-dUTP to prepare hybridization probes. The mixed probes were hybridized to the cDNA microarray. After high-stringent washing, the fluorescent signals on cDNA microarray chip were scanned and analyzed.
RESULTS: Among the 4 096 target genes, 82 differentially expressed genes were identified between the two groups. There were 18 novel genes, 33 expression sequence tags, and 31 previously reported genes. The selected genes may be divided into four classes: genes modulating cellular adhesion, genes regulating cellular energy, glucose and protein metabolism, early response genes and other genes.
CONCLUSION: A total of 82 genes that may be relevant to cold preservation/reperfusion injury in small intestinal allografts are identified. Abnormal adhesion between polymorphonuclears and endothelia and failure in energy, glucose and protein metabolism of the grafts may contribute to preservation/reperfusion injury. The functions of the novel genes identified in our study need to be clarified further.
Collapse
Affiliation(s)
- Shu-Feng Wang
- Department of General Surgery, First Hospital, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
| | | | | | | |
Collapse
|
|
8
|
Farmer DG, Shen XD, Amersi F, Anselmo D, Ma JP, Ke B, Gao F, Dry S, Fernandez S, Shaw GD, McDiarmid SV, Busuttil RW, Kupiec-Weglinski J. CD62 Blockade with P-Selectin Glycoprotein Ligand-Immunoglobulin Fusion Protein Reduces Ischemia-Reperfusion Injury After Rat Intestinal Transplantation. Transplantation 2005; 79:44-51. [PMID: 15714168 DOI: 10.1097/01.tp.0000146965.64706.e8] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Intestinal transplantation (ITx) is severely limited by ischemia-reperfusion (I/R) injury. This study investigates I/R injury and ameliorates its consequences by using a recombinant protein targeted against selectins (recombinant P-selectin glycoprotein ligand-immunoglobulin [rPSGL-Ig]). METHODS An isogeneic model of ITx was undertaken with control animals (no therapy) and treatment animals (rPSGL-Ig). Survival was assessed. Separate groups underwent an analysis examining tissue at multiple time points after I/R injury including histopathology; myeloperoxidase staining; immunostaining for CD3 and ED2; polymerase chain reaction analysis of interleukin (IL)-8/cytokine-inducible neutrophil chemoattractant, IL1beta, IL-6, interferon-gamma, IL-2, IL-4, and IL10; and western blots for hemoxygenase-1, BCL-2, and BCL-xl. Standard statistical analysis was undertaken. RESULTS Treatment with rPSGL-Ig resulted in significantly improved survival after ITx. Analysis demonstrated diminished injury on histopathology and reduced tissue infiltration of neutrophils and lymphocytes. Significant differences in the cytokine profile after ITx were seen between the two groups including the production of inflammatory cytokines at 24 hr and the Th1 and Th2 cytokines at 2 and 4 hr. Last, treatment resulted in increased production of hemoxygenase, BCL-2, and BCL-xl. CONCLUSION The results of this investigation of I/R injury after ITx revealed that rPSGL-Ig treatment led to marked improvement in outcome. The mechanism of action seems to involve the blockade of neutrophil and lymphocyte infiltration leading to a decreased inflammatory response possibly driven by Th2 cytokines. The results not only lend insight into the mechanisms behind I/R injury after ITx but also demonstrate a potential therapeutic modality to ameliorate its consequences.
Collapse
Affiliation(s)
- Douglas G Farmer
- Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
9
|
Carmody IC, Meng L, Shen XD, Anselmo D, Gao F, Ke B, Ma JP, Kupiec-Weglinski JW, McDiarmid SV, Busuttil RW, Shaw G, Farmer DG. P-selectin knockout mice have improved outcomes with both warm ischemia and small bowel transplantation. Transplant Proc 2004; 36:263-4. [PMID: 15050128 DOI: 10.1016/j.transproceed.2003.12.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
AIM To analyze the role of P-selectin in intestinal ischemia and reperfusion injury (IRI) using murine models. METHODS A model of warm IRI wherein the SMA was occluded for 100 minutes was undertaken in the following groups (10 mice per group): Group 1 (control) wild-type (WT) C57BL6, no treatment; Group 2: 0.4 mg/kg of r-PSGL1-lg 10 minutes before and after clamping; Group 3: PSGL KO mice. Survival was assessed at 7 days; the intestine was assayed for histopathology, apoptosis, myeloperoxidase (MPO), IL1, and TNF. A second model of cold IRI followed by intestinal transplantation (IT) was undertaken in the following groups (two mice per group): Group A WT --> WT: Group B PSGL KO --> WT (1-hour ischemia); Group C: PSGL KO --> WT (2 hour ischemia). Survival only was assessed. RESULTS Survival was 50% in group 1, 90% in group 2, and 100% in group 3. Graded histopathology and crypt apoptosis demonstrated significantly less injury in groups B and C. MPO was not different between groups. IL1 and TNF were significantly reduce in groups 2 and 3. Following IT, survival was <12 hours in group A, >7 days in group B, and <72 hours in group C. CONCLUSION This study clearly demonstrates the importance of P-selectin in warm and cold IRI in that the blockade of P-selectin using rPSGL1-lg or the absence of P-selectin using KO mice confers a survival advantage and reduction in tissue injury. The mechanism is unclear but appears to be independent of neutrophil infiltration.
Collapse
Affiliation(s)
- I C Carmody
- Dumont-UCLA Transplant Program, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
10
|
Jones TR, Shirasugi N, Adams AB, Pearson TC, Larsen CP. Intravital microscopy identifies selectins that regulate T cell traffic into allografts. J Clin Invest 2004; 112:1714-23. [PMID: 14660747 PMCID: PMC281648 DOI: 10.1172/jci19391] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
T cell homing to sites of injury and inflammation is a critical step for adaptive immune responses. While much has been learned regarding T cell homing to lymphoid tissues, few studies have directly observed trafficking events during an effector response. In this study, we developed a model that uses intravital fluorescence videomicroscopy to determine the molecules critical to T cell rolling within skin allograft microvasculature during the effector phase of the rejection response. Additional studies were performed to quantify T cell infiltrates as rejection progressed. We found that P-selectin and E-selectin expressed on postcapillary venules play overlapping roles in the recruitment of activated T cells in a SCID reconstitution model of skin graft rejection and are important in T cell accumulation at the graft site. Surprisingly, we also found that naive T cells are recruited and accumulate via constitutive T cell L-selectin and upregulated L-selectin ligands on rejecting allograft vasculature. These data indicated that a specific retinue of molecules is upregulated during the rejection response, and they suggest potential future therapeutic targets.
Collapse
Affiliation(s)
- Thomas R Jones
- Emory Transplant Center and Department of Surgery, Emory Universuty School of Medicine, Atlanta, Georgia 30322, USA
| | | | | | | | | |
Collapse
|
|
11
|
Abstract
AIM: To investigate the early protective effect of ischemic preconditioning on small intestinal graft in rats.
METHODS: SD rats were randomly divided into the following groups: sham operation group (S group, n = 6), small bowel transplantation group (SBT group, n = 12), ischemic preconditioning plus small bowel transplantation group (ISBT group, n = 12). Heterotopic SBT was performed with a technique modified from that described by Monchik et al When the graft was revascularized successfully and reperfused for 1 h, samples were obtained from the different groups. Laminin was analyzed with immunohistochemical staining. Quantitative analysis of laminin positive signals was performed using image acquiring analysis system. Apoptotic epithelia of small intestinal graft were detected by the TdT-mediated dUTP nick end labeling method. The morphological change of epithelial basement membrane was observed by transmission electron microscopy.
RESULTS: The mean optical density value of laminin positive signals was 39.52 ± 2.60, 13.53 ± 0.44, 25.40 ± 1.79, respectively, in S, SBT and ISBT groups. The average optical density value of laminin positive products in SBT group was sharply lower than that in S group (P < 0.05). However, the mean optical density value of laminin positive products in ISBT group was significantly higher than that in SBT group (P < 0.05). The apoptotic index (AI) in S, SBT and ISBT group was 2.2 ± 0.83,30.8 ± 3.2, 13.2 ± 2.86, respectively. The AI in SBT group was significantly higher than that in S group (P < 0.05), and AI in ISBT group was sharply lower than that in SBT group (P < 0.05). On transmission electron microscopy, the epithelial basement membrane in S group stayed normal, but in SBT group it became disrupted and collapsed, even disappeared. The lesion of epithelial basement membrane in ISBT group was slighter compared with that in SBT group.
CONCLUSION: Ischemic preconditioning has an early protective effect on epithelial cells and extracellur matrix of small intestinal graft. Inhibition of epithelial cell apoptosis may be one of the mechanisms of ischemic preconditioning.
Collapse
Affiliation(s)
- Shu-Feng Wang
- Department of General Surgery, First Hospital, Xi'an Jiaotong University, Xi'an 710061, Shannxi Province, China.
| | | |
Collapse
|
|
12
|
Haddad W, Cooper CJ, Zhang Z, Brown JB, Zhu Y, Issekutz A, Fuss I, Lee HO, Kansas GS, Barrett TA. P-selectin and P-selectin glycoprotein ligand 1 are major determinants for Th1 cell recruitment to nonlymphoid effector sites in the intestinal lamina propria. J Exp Med 2003; 198:369-77. [PMID: 12885868 PMCID: PMC2194084 DOI: 10.1084/jem.20020691] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The recruitment of activated T cell subsets to sites of effector immune responses is mediated by homing receptors induced upon activation in secondary lymphoid tissue. Using an adoptive transfer model, the intestinal recruitment of CD4+ T cells activated with intraperitoneal antigen in complete Freund's adjuvant was examined. The data demonstrate that activated CD4+ T cells recruited to intestinal Peyer's patches (PP) and lamina propria (LP) up-regulate functional P-selectin glycoprotein ligand 1 (PSGL-1). Blockade of IL-12 inhibited functional PSGL-1 expression and reduced PP and LP CD4+ T cell recruitment by >40%. P-selectin blockade reduced LP recruitment of activated cells by 56% without affecting PP recruitment. Studies of mice examined 3 d after adoptive transfer of differentiated T cell subsets revealed that Th1 but not Th2 cells were recruited to small intestine PP and LP. Mucosal addressin cell adhesion molecule blockade reduced Th1 recruitment to PP by 90% and to LP by >72%, whereas P-selectin blockade reduced Th1 recruitment to PP by 18% and Th1 recruitment to LP by 84%. These data suggest that IL-12-induced functional PSGL-1 expression is a major determinant for the recruitment of Th1 effector cells to noninflamed as well as inflamed intestine.
Collapse
Affiliation(s)
- Wael Haddad
- Dept. of Medicine, Northwestern University Medical School, 745 N. Fairbanks, Searle 10-455, Chicago, IL 60611, USA
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Chen JL, Zhou T, Chen WX, Zhu JS, Chen NW, Zhang MJ, Wu YL. Effect of tetramethylpyrazine on P-selectin and hepatic/renal ischemia and reperfusion injury in rats. World J Gastroenterol 2003; 9:1563-6. [PMID: 12854164 PMCID: PMC4615505 DOI: 10.3748/wjg.v9.i7.1563] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of tetramethylpyrazine on hepatic/renal ischemia and reperfusion injury in rats.
METHODS: Hepatic/renal function, histopathological changes, and hepatic/renal P-selectin expression were studied with biochemical measurement and immunohistochemistry in hepatic/renal ischemia and reperfusion injury in rat models.
RESULTS: Hepatic/renal insufficiency and histopathological damage were much less in the tetramethylpyrazine-treated group than those in the saline-treated groups. Hepatic/renal P-selectin expression was down regulated in the tetramethylpyrazine-treated group.
CONCLUSION: P-selectin might mediate neutrophil infiltration and contribute to hepatic/renal ischemia and reperfusion injury. Tetramethylpyrazine might prevent hepatic/renal damage induced by ischemia and reperfusion injury through inhibition of P-selectin.
Collapse
Affiliation(s)
- Jin-Lian Chen
- Department of Gastroenterology, Shanghai Sixth People's Hospital, Shanghai Jiao-Tong University, Shanghai 200233, China.
| | | | | | | | | | | | | |
Collapse
|
|
14
|
Abstract
The shortage of organs has led centers to expand their criteria for the acceptance of marginal donors. The combination of multiple marginal factors seems to be additive on graft injury. In this review, the utility of various marginal donors in patients requiring liver transplantation will be described, including older donors, steatotic livers, non-heart-beating donors, donors with viral hepatitis, and donors with malignancies. The pathophysiology of the marginal donor will be discussed, along with strategies for minimizing the ischemia reperfusion injury experienced by these organs. Finally, new strategies for improving the function of the marginal/expanded donor liver will be reviewed.
Collapse
Affiliation(s)
- Ronald W Busuttil
- Department of Surgery, Division of Liver and Pancreas Transplantation, Dumont-UCLA Transplant Center, Los Angeles, CA 90095, USA.
| | | |
Collapse
|
|
15
|
|