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Warm Ischemia (warm + ischemia)

Distribution by Scientific Domains

Medical Sciences	100%

Terms modified by Warm Ischemia

warm ischemia time

Selected Abstracts

Anti-thrombin Therapy During Warm Ischemia and Cold Preservation Prevents Chronic Kidney Graft Fibrosis in a DCD Model

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010
F. Favreau
Ischemia reperfusion injury (IRI) is pivotal for renal fibrosis development via peritubular capillaries injury. Coagulation represents a key mechanism involved in this process. Melagatran® (M), a thrombin inhibitor, was evaluated in an autotransplanted kidney model, using Large White pigs. To mimic deceased after cardiac death donor conditions, kidneys underwent warm ischemia (WI) for 60 min before cold preservation for 24 h in University of Wisconsin solution. Treatment with M before WI and/or in the preservation solution drastically improved survival at 3 months, reduced renal dysfunction related to a critical reduction in interstitial fibrosis, measured by Sirius Red staining. Tissue analysis revealed reduced expression of transforming growth factor-, (TGF-,) and activation level of its effectors phospho-Smad3, Smad4 and connective tissue growth factor (CTGF) after M treatment. Fibrinolysis activation was also observed, evidenced by downregulation of PAI-1 protein and gene expression. In addition, M reduced S100A4 expression and vimentin staining, which are markers for epithelial mesenchymal transition, a major pathway to chronic kidney fibrosis. Finally, expression of oxidative stress markers Nox2 and iNOS was reduced. We conclude that inhibition of thrombin is an effective therapy against IRI that reduces chronic graft fibrosis, with a significantly positive effect on survival. [source]

Extracorporeal Support: Improves Donor Renal Graft Function After Cardiac Death

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010
A. Rojas-Pena
Donors after cardiac death (DCD) could increase the organ pool. Data supports good long-term renal graft survival. However, DCDs are <10% of deceased donors in the United States, due to delayed graft function, and primary nonfunction. These complications are minimized by extracorporeal support after cardiac death (ECS-DCD). This study assesses immediate and acute renal function from different donor types. DCDs kidneys were recovered by conventional rapid recovery or by ECS, and transplanted into nephrectomized healthy swine. Warm ischemia of 10 and 30 min were evaluated. Swine living donors were controls (LVD). ECS-DCDs were treated with 90 min of perfusion until organ recovery. After procurement, kidneys were cold storage 4,6 h. Renal vascular resistance (RVR), urine output (UO), urine protein concentration (UrPr) and creatinine clearance (CrCl), were collected during 4 h posttransplantation. All grafts functioned with adequate renal blood flow for 4 h. RVR at 4 h posttransplant returned to baseline only in the LVD group (0.36 mmHg/mL/min ± 0.03). RVR was higher in all DCDs (0.66 mmHg/mL/min ± 0.13), without differences between them. UO was >50 mL/h in all DCDs, except in DCD-30 (6.8 mL/h ± 1.7). DCD-30 had lower CrCl (0.9 mL/min ± 0.2) and higher UrPr >200 mg/dL, compared to other DCDs >10 mL/min and <160 mg/dL, respectively. Normothermic ECS can resuscitate kidneys to transplantable status after 30 min of cardiac arrest/WI. [source]

Induction of cellular resistance against Kupffer cell,derived oxidant stress: A novel concept of hepatoprotection by ischemic preconditioning

HEPATOLOGY, Issue 2 2003
Rolf J. Schauer
Ischemic preconditioning (IP) triggers protection of the liver from prolonged subsequent ischemia. However, the underlying protective mechanisms are largely unknown. We investigated whether and how IP protects the liver against reperfusion injury caused by Kupffer cell (KC)-derived oxidants. IP before 90 minutes of warm ischemia of rat livers in vivo significantly reduced serum alanine aminotransferase (AST) levels and leukocyte adherence to sinusoids and postsinusoidal venules during reperfusion. This protective effect was mimicked by postischemic intravenous infusion of glutathione (GSH), an antioxidative strategy against KC-derived H2O2. Interestingly, no additional protection was achieved by infusion of GSH to preconditioned animals. These findings and several additional experiments strongly suggest IP mediated antioxidative effects: IP prevented oxidant cell injury in isolated perfused rat livers after selective KC activation by zymosan. Moreover, IP prevented cell injury and pertubations of the intracellular GSH/GSSG redox system caused by direct infusion of H2O2 (0.5 mmol/L). IP-mediated resistance against H2O2 could neither be blocked by the adenosine A2a antagonist DMPX nor mimicked by A2a agonist CGS21680. In contrast, H2O2 resistance was abolished by the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, but induced when p38 MAPK was directly activated by anisomycin. In conclusion, we propose a novel concept of hepatoprotection by IP: protection of liver cells by enhancing their resistance against KC-derived H2O2. Activation of p38 MAPK and preservation of the intracellular GSH/oxidized glutathione (GSSG) redox system, but not adenosine A2a receptor stimulation, seems to be pivotal for the development of H2O2 resistance in preconditioned livers. [source]

Stat4 and Stat6 signaling in hepatic ischemia/reperfusion injury in mice: HO-1 dependence of Stat4 disruption-mediated cytoprotection

HEPATOLOGY, Issue 2 2003
Xiu-Da Shen
Ischemia/reperfusion (I/R) injury remains an important problem in clinical organ transplantation. There is growing evidence that T lymphocytes, and activated CD4+ T cells in particular, play a key role in hepatic I/R injury. This study analyzes the role of signal transducer and activator of transcription 4 (Stat4) and Stat6 signaling in liver I/R injury. Using a partial lobar warm ischemia model, groups of wild-type (WT), T cell,deficient, Stat4-/Stat6-deficient knockout (KO) mice were assessed for the extent/severity of I/R injury. Ninety minutes of warm ischemia followed by 6 hours of reperfusion induced a fulminant liver failure in WT and Stat6 KO mice, as assessed by hepatocellular damage (serum alanine aminotransferase [sALT] levels), neutrophil accumulation (myeloperoxidase [MPO] activity) and histology (Suzuki scores). In contrast, T cell deficiency (nu/nu mice) or disruption of Stat4 signaling (Stat4 KO mice) reduced I/R insult. Unlike adoptive transfer of WT or Stat6-deficient T cells, infusion of Stat4-deficient T cells failed to restore hepatic I/R injury and prevented tumor necrosis factor , (TNF-,) production in nu/nu mice. Diminished TNF-,/Th1-type cytokine messenger RNA (mRNA)/protein elaborations patterns, along with overexpression of heme oxygenase-1 (HO-1),accompanied hepatic cytoprotection in Stat4 KO recipients. In contrast, HO-1 depression restored hepatic injury in otherwise I/R resistant Stat4 KOs. In conclusion, Stat4 signaling is required for, whereas Stat4 disruption protects against, warm hepatic I/R injury in mice. The cytoprotection rendered by Stat4 disruption remains HO-1,dependent. [source]

Enhanced expression of B7-1, B7-2, and intercellular adhesion molecule 1 in sinusoidal endothelial cells by warm ischemia/reperfusion injury in rat liver

HEPATOLOGY, Issue 4 2001
Naosuke Kojima
To elucidate a role of costimulatory molecule and cell adhesion molecule in hepatic ischemia/reperfusion injury, we examined an alteration in B7-1 (CD80), B7-2 (CD86), and intercellular adhesion molecule 1 (ICAM-1; CD54) expression in the rat liver after warm ischemia/reperfusion injury. To induce hepatic warm ischemia in a rat model, both portal vein and hepatic artery entering the left-lateral and median lobes were occluded by clamping for 30 minutes or 60 minutes, and then reperfused for 24 hours. B7-1, B7-2, and ICAM-1 expressions in the liver were analyzed by immunofluorescence staining and real-time reverse transcription polymerase chain reaction (RT-PCR). Although B7-1 and B7-2 expressions were at very low levels in the liver tissues from normal or sham-operated control rats, both B7-1 and B7-2 expressions were enhanced at protein and messenger RNA (mRNA) levels in the affected, left lobes after warm ischemia/reperfusion. ICAM-1 protein and mRNA were constitutively expressed in the liver of normal and sham-operated control rats, and further up-regulated after warm ischemia/reperfusion. Localization of increased B7-1, B7-2, and ICAM-1 proteins, as well as von Willebrand factor as a marker protein for endothelial cells, was confined by immunofluorescence staining to sinusoidal endothelial cells in hepatic lobules. Data from quantitative real-time RT-PCR analysis revealed that B7-1 and B7-2 mRNA levels were elevated in hepatic lobes after warm ischemia/reperfusion (5.13- and 52.9-fold increase, respectively), whereas ICAM-1 mRNA expression was rather constitutive but further enhanced by warm ischemia/reperfusion (4.24-fold increase). These results suggest that hepatic sinusoidal endothelial cells play a pivotal role as antigen-presenting cells by expressing B7-1 and B7-2 in warm hepatic ischemia/reperfusion injury, and that B7-1 and/or B7-2 might be the primary target to prevent early rejection and inflammatory reactions after hepatic ischemia/reperfusion injury associated with liver transplantation. [source]

Complete robotic-assistance during laparoscopic living donor nephrectomies: An evaluation of 38 procedures at a single site

INTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2007
Jacques Hubert
Objective: To evaluate our initial experience with entirely robot-assisted laparoscopic live donor (RALD) nephrectomies. Methods: From January 2002 to April 2006, we carried out 38 RALD nephrectomies at our institution, using four ports (three for the robotic arms and one for the assistant). The collateral veins were ligated, and the renal arteries and veins clipped, after completion of ureteral and renal dissection. The kidney was removed via a suprapubic Pfannenstiel incision. A complementary running suture was carried out on the arterial stump to secure the hemostasis. Results: Mean donor age was 43 years. All nephrectomies were carried out entirely laparoscopically, without complications and with minimal blood loss. Mean surgery time was 181 min. Average warm ischemia and cold ischemia times were 5.84 min and 180 min, respectively. Average donor hospital stay was 5.5 days. None of the transplant recipients had delayed graft function. Conclusions: Robot-assisted laparoscopic live donor nephrectomy can be safely carried out. Robotics enhances the laparoscopist's skills, enables the surgeon to dissect meticulously and to prevent problematic bleeding more easily. Donor morbidity and hospitalization are reduced by the laparoscopic approach and the use of robotics allows the surgeon to work under better ergonomic conditions. [source]

Short-term administration of (-)-epigallocatechin gallate reduces hepatic steatosis and protects against warm hepatic ischemia/reperfusion injury in steatotic mice

LIVER TRANSPLANTATION, Issue 3 2005
Ryan N. Fiorini
Hepatic steatosis increases the extent of cellular injury incurred during ischemia/reperfusion (I/R) injury. (-)-Epigallocatechin gallate (EGCG), the major flavonoid component of green tea (camellia sinensis) is a potent antioxidant that inhibits fatty acid synthase (FAS) in vitro. We investigated the effects of EGCG on hepatic steatosis and markers of cellular damage at baseline and after I/R injury in ob/ob mice. Animals were pretreated with 85 mg/kg EGCG via intraperitoneal (ip) injection for 2 days or oral consumption in the drinking water for 5 days before 15 minutes of warm ischemia and 24 hours of reperfusion. After EGCG administration, total baseline hepatic fat content decreased from baseline. Palmitic acid and linoleic acid levels also were reduced substantially in all ECGC-treated animals before I/R. Alanine aminotransferase (ALT) levels decreased in all EGCG-treated animals compared with control animals after I/R. Histologic analysis demonstrated an average decrease of 65% necrosis after EGCG administration. EGCG administration also increased resting hepatic energy stores as determined by an increase in cellular adenosine triphosphate (ATP) with a concomitant decrease in uncoupling protein 2 (UCP2) before I/R. Finally, there was an increased level of glutathione (GSH) in the EGCG-treated mice compared with the vehicle-treated mice both at baseline and after I/R. In conclusion, taken together, this study demonstrates that treatment with ECGC by either oral or ip administration, significantly protects the liver after I/R, possibly by reducing hepatic fat content, increasing hepatic energy status, and functioning as an antioxidant. (Liver Transpl 2005;11:298,308.) [source]

Effect of HTK on the microcirculation in the rat cremaster muscle during warm ischemia and reperfusion

MICROSURGERY, Issue 2 2005
Jacqueline Bastiaanse M.D.
Histidine-tryptophan-ketoglutarate (HTK) preserves rat muscle function during cold storage. We examined the effect of HTK perfusion on preservation of microvascular function during 4 h of warm ischemia and subsequent reperfusion (I/R) in the rat cremaster muscle. Leukocyte-endothelium interactions, capillary perfusion, and arteriole diameters were quantified prior to HTK-perfusion and/or ischemia, and at 0, 1, and 2 h after restoration of blood flow. In all groups, the number of rolling leukocytes increased with time, whereas I/R induced a slight increase in leukocyte adhesion. After ischemia, capillary perfusion rapidly recovered to about 50% and returned to near normal (90%) after 2 h. HTK at 22°C did not affect the assessed microcirculation variables, whereas HTK at 4°C reduced leukocyte rolling, but not adhesion. Therefore, microvascular function of HTK-perfused muscles was not better preserved during warm I/R than that of nonperfused muscles. Contrary to other preservation solutions, HTK perfusion in itself was not detrimental to the microcirculation. © 2005 Wiley-Liss, Inc. Microsurgery 25:174,180, 2005. [source]

Delayed penile replantation after prolonged warm ischemia

MICROSURGERY, Issue 2 2001
Afshin Mosahebi
We report a case of microsurgical replantation of traumatic self-amputation of penis after prolonged warm ischemia as a result of delayed presentation. At 12 weeks postoperative follow-up evaluation, the patient exhibited good urinary flow, spontaneous erection, and a normal response to pharmacological stimulation. © 2001 Wiley-Liss, Inc. MICROSURGERY 21:52,54 2001 [source]

Alloimmune Activation Enhances Innate Tissue Inflammation/Injury in a Mouse Model of Liver Ischemia/Reperfusion Injury

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010
X. Shen
The deleterious sensitization to donor MHC Ags represents one of the most challenging problems in clinical organ transplantation. Although the role of effector/memory T cells in the rejection cascade has been extensively studied, it remains unknown whether and how these ,Ag-specific' cells influence host innate immunity, such as tissue inflammation associated with ischemia and reperfusion injury (IRI). In this study, we analyzed how allogeneic skin transplant (Tx) affected the sequel of host's own liver damage induced by partial warm ischemia and reperfusion. Our data clearly showed that allo-Tx recipients had increased inflammatory response against IR insult in their native livers, as evidenced by significantly more severe hepatocelluar damage, compared with syngeneic Tx recipient controls, and determined by serum ALT levels, liver histology (Suzuki's score) and intrahepatic proinflammatory gene inductions (TNF-,, IL-1, and CXCL10). The CD4 T cells, but neither CD8 nor NK cells, mediated the detrimental effect of allo-Ag sensitization in liver IRI. Furthermore, CD154, but not IFN-,, was the key mechanism in allo-Tx recipients to facilitate IR-triggered liver damage. These results provide new evidence that alloreactive CD4 T cells are capable of enhancing innate tissue inflammation and organ injury via an Ag-nonspecific CD154-dependent but IFN-, independent mechanism. [source]

Anti-thrombin Therapy During Warm Ischemia and Cold Preservation Prevents Chronic Kidney Graft Fibrosis in a DCD Model

Peritoneal Cooling May Provide Improved Protection for Uncontrolled Donors After Cardiac Death: An Exploratory Porcine Study

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009
A. P. Navarro
Uncontrolled donation after cardiac death (DCD) renal transplantation relies on rapid establishment of organ preservation interventions. We have developed a model of the uncontrolled DCD, comparing current in situ perfusion (ISP) techniques with additional peritoneal cooling (PC). Ten pigs were killed and subjected to a 2 h ischemia period. The ISP group modeled current DCD protocols. The PC group (PC) modeled current protocols plus PC. Two animals were used as controls and subjected to 2 h of warm ischemia. Core renal temperature and microdialysis markers of ischemia were measured. Preservation interventions began at 30 min, with rapid laparotomy and kidney recovery performed at 2 h, prior to machine perfusion viability testing. The final mean renal temperature achieved in the ISP group was 26.3°C versus 16.9°C in the PC group (p = 0.0001). A significant cryopreservation benefit was suggested by lower peak microdialysate lactate and glycerol levels (ISP vs. PC, p = 0.0003 and 0.0008), and the superiority of the PC group viability criteria (p = 0.0147). This pilot study has demonstrated significant temperature, ischemia protection and viability assessment benefits with the use of supplementary PC. The data suggests a need for further research to determine the potential for reductions in the rates of ischemia-related clinical phenomena for uncontrolled DCDs. [source]

Survival Outcomes Following Liver Transplantation (SOFT) Score: A Novel Method to Predict Patient Survival Following Liver Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2008
A. Rana
It is critical to balance waitlist mortality against posttransplant mortality. Our objective was to devise a scoring system that predicts recipient survival at 3 months following liver transplantation to complement MELD-predicted waitlist mortality. Univariate and multivariate analysis on 21 673 liver transplant recipients identified independent recipient and donor risk factors for posttransplant mortality. A retrospective analysis conducted on 30 321 waitlisted candidates reevaluated the predictive ability of the Model for End-Stage Liver Disease (MELD) score. We identified 13 recipient factors, 4 donor factors and 2 operative factors (warm and cold ischemia) as significant predictors of recipient mortality following liver transplantation at 3 months. The Survival Outcomes Following Liver Transplant (SOFT) Score utilized 18 risk factors (excluding warm ischemia) to successfully predict 3-month recipient survival following liver transplantation. This analysis represents a study of waitlisted candidates and transplant recipients of liver allografts after the MELD score was implemented. Unlike MELD, the SOFT score can accurately predict 3-month survival following liver transplantation. The most significant risk factors were previous transplantation and life support pretransplant. The SOFT score can help clinicians determine in real time which candidates should be transplanted with which allografts. Combined with MELD, SOFT can better quantify survival benefit for individual transplant procedures. [source]

Improved Outcomes in Islet Isolation and Transplantation by the Use of a Novel Hemoglobin-based O2 Carrier

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2006
J. G. Avila
During isolation, islets are exposed to warm ischemia. In this study, intraductal administration of oxygenated polymerized, stroma-free hemoglobin-pyridoxalated (Poly SFH-P) was performed to improve O2 delivery. Rat pancreata subjected to 30-min warm ischemia were perfused intraductally with collagenase in oxygenated Poly SFH-P/RPMI or RPMI (control). PO2 was increased by Poly SFH-P (381.7 ± 35.3 mmHg vs. 202.3 ± 28.2, p = 0.01) and pH maintained within physiological range (7.4,7.2 vs. 7.1,6.6, p = 0.009). Islet viability (77%± 4.6 vs. 63%± 4.7, p = 0.04) was improved and apoptosis lower with Poly SFH-P (caspase-3: 34,714 ± 2167 vs. 45,985 ± 1382, respectively, p = 0.01). Poly SFH-P improved islet responsiveness to glucose as determined by increased intracellular Ca2+ levels and improved insulin secretion (SI 5.4 ± 0.1 vs. 3.1 ± 0.2, p = 0.03). Mitochondrial integrity was improved in Poly SFH-P-treated islets, which showed higher percentage change in membrane potential after glucose stimulation (14.7%± 1.8 vs. 9.8 ± 1.4, respectively, p < 0.05). O2 delivery by Poly SFH-P did not increase oxidative stress (GSH 7.1 ± 2.9 nm/mg protein for Poly SFH-P vs. 6.8 ± 2.4 control, p = 0.9) or oxidative injury (MDA 1.8 ± 0.9 nmol/mg protein vs. 6.2 ± 2.4, p = 0.19). Time to reach normoglycemia in transplanted diabetic nude mice was shorter (1.8 ± 0.4 vs. 7 ± 2.5 days, p = 0.02), and glucose tolerance improved in the Poly SFH-P group (AUC 8106 ± 590 vs. 10,863 ± 946, p = 0.03). Oxygenated Poly SFH-P improves islet isolation and transplantation outcomes by preserving mitochondrial integrity. [source]

The cadaveric kidney and the organ shortage , a perspective review

CLINICAL TRANSPLANTATION, Issue 6 2001
L Brasile
Despite the technical and logistical hurdles that must be overcome with the reintroduction of non-heartbeating donor kidneys, the potential of these organs represents the only near-term solution for effectively alleviating the growing disparity between demand and supply. This review provides an argumentative overview of the history of cadaveric kidney transplantation. During the early years of transplantation retrieval of kidneys from non-heartbeating donors necessitated a prolonged period of warm ischemic exposure, with a corresponding minimal ex vivo period since organ preservation was in its infancy. Today we have the inverse situation where warm ischemic times are quite limited and hypothermic preservation times average 24 h because organs are shipped to remote centers due to mandated organ sharing algorithms. The recent experience with the reintroduction of non-heartbeating donors has necessitated combining the worst aspects from both eras: substantial warm ischemia with prolonged hypothermic preservation. Nevertheless, recent results from several transplant groups poignantly highlight the potential of this approach in expanding the organ donor pool. [source]