Total Warm Ischemia and Reperfusion Impairs Flow In All Rat Gut Layers but Increases Leukocytevessel Wall Interactions In the Submucosa Only (original) (raw)
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Transplantation Proceedings, 2004
The objective of this study was to evaluate the effect of ischemic preconditioning upon lesions produced by ischemia-reperfusion of the small intestine. Thirty EPM-1 Wistar rats were randomly distributed into three groups: ischemic preconditioning (IPC; n ϭ 12), ischemia-reperfusion (I/R; n ϭ 12), and control (C; n ϭ 6). Laparotomy permitted isolation of the mesenteric artery for clamping. The animals were heparinized and hydrated. IPC was induced by: 10 minutes of ischemia followed by 10 minutes of reperfusion and then 50 minutes ischemia followed by another 30 minutes reperfusion. Group I/R was submitted to the same protocol except for the 20 minutes of preconditioning. Group C animals underwent only laparotomy for 100 minutes. After reperfusion small intestine fragments were examined histologically. Blood samples were obtained to measure LDH and lactate prior to euthanasia. Lactate values were significantly lower in the IPC as compared to I/R group, 39 versus 67 mg/dL, respectively (P Յ .05). However, neither IPC (grade 3) lesions of the mucosa versus I/R (grade 4) nor LDH values (PCI ϭ 680, I/R ϭ 873 U/L) were statistically different. Thus No morphological evidence of protection was observed following ischemic preconditioning.
Effect of reperfusion injury from distant ischemia to small intestine
Medical Journal of Indonesia
BACKGROUND The ileum is the most vulnerable part of the small intestine that plays an important role as the motor of multisystem organ failure. Villous damage is demonstrated after ligation of supply artery in mice; however, there is no study on the ileum after distant ischemic organs. Thus, this study was aimed to find out ileal villous changes following reperfusion injury, the protective effects of ischemic hypothermia and ischemic preconditioning. METHODS An experimental study conducted enrolled 21 subjects of Oryctolagus cuniculus. Ischemia is induced by ligation of the femoral artery for 4 hours. Eight hours after ligation was released, ileum and duodenal specimens were taken through laparotomy. H&E stained specimens were examined for histomorphological changes. Villi change scores, tissue level of hypoxia-inducible factor-1α (HIF-1α), malondialdehyde (MDA), and occludin were statistically analyzed in four treatment groups, namely ischemia, ischemic hypothermia, ischemic preconditioning, and control. RESULTS Intestinal villi changes were found following ischemic-induced arterial ligation. Ileal villi changes showed differences with the duodenum and controls as indicated by the villi damage scores, increased tissue HIF-1α and MDA, and decreased occludin levels. Ileal villi changes in the ischemic and ischemic hypothermia groups showed significant changes with controls; whereas the ischemic preconditioning group showed no significant differences. CONCLUSIONS Ischemia at a distance leads to both histomorphological and biochemical damage of the ileal villi and disrupts the integrity of the intestinal mucosal barrier. In addition, the study showed a protective effect of ischemic preconditioning.
Superior mesenteric artery occlusion models shock-induced gut ischemia-reperfusion
Journal of Surgical Research, 2004
Background. Superior mesenteric artery occlusion (SMAO) is a simple and reproducible model of shockinduced gut ischemia/reperfusion, but some argue that it is not clinically relevant. The purpose of the current study was to compare SMAO to a standard model of controlled hemorrhage (CH) and uncontrolled hemorrhage (UH). Methods. Rats had femoral lines and a jejunal mucosal laser Doppler placed followed by SMAO (60 min of ischemia, no resuscitation), controlled hemorrhage (40 mm Hg for 60 min, 2:1 resuscitation shed blood and lactated Ringers), or uncontrolled hemorrhage (liver injury, 3:1 resuscitation with lactated Ringers). Base deficit, lactate, and jejunal mucosal flow (as a percentage of baseline) were recorded during ischemia and for 120 min after reperfusion. Jejunal tissue was harvested for morphological evaluation. Comparison among groups was by analysis of variance (ANOVA), and significance was set at P < 0.05. Results. Mucosal blood flow was similar among groups at the onset of reperfusion (CH, 16.9 ؎ 5.0% versus UH, 10.9 ؎ 3.1% versus SMAO, 13.9 ؎ 6.2%) and during the initial period of reperfusion. By 120 min, however, flow in CH (75.4 ؎ 2.5%) was significantly higher that in either UH (36.4 ؎ 13.1%) or SMAO (31.7 ؎ 8.4%). Histological injury was less with CH, while base deficit was significantly higher in CH at the onset of reperfusion (؊24 ؎ 2 versus UH, ؊10 ؎ 3 and SMAO, ؊6 ؎ 3 mM/L) but comparable by the end (CH, ؊17 ؎ 4 versus UH, ؊16 ؎ 3 and SMAO, ؊17 ؎ 2 mM/L). Conclusion. SMAO is a clinically relevant model of shock-induced gut ischemia/reperfusion.
Leukocyte adhesion and hepatic microvascular responses to intestinal ischemia/reperfusion in rats
Gastroenterology, 1996
Background & Aims: Although it has been reported that sumably because the vasculature of these tissues are cougut ischemia/reperfusion (I/R) elicits neutrophil-depled in series with the intestinal circulation. Several rependent liver dysfunction, little is known about the kiports describe increased pulmonary vascular permeability netics of leukocyte accumulation in the hepatic microin response to gut I/R, which was attenuated in animals circulation after gut I/R. The aim of this study was to pretreated with monoclonal antibodies (MAbs) directed determine the temporal relationship between leukocyte against leukocyte or endothelial cell adhesion molesequestration and oxidative stress in rat liver after occules. 4,5 The pulmonary microvascular responses to gut clusion (30 minutes) and reperfusion (60 minutes) of I/R have been characterized in some detail, but relatively the superior mesenteric artery and assess the effects little is known about the effects of gut I/R on the liver. of neutrophil depletion or immunoneutralization of ei-Some reports describe hepatocellular changes associther intercellular adhesion molecule 1 (ICAM-1) or the ated with gut I/R and implicate neutrophils as a mediator leukocyte adhesion glycoprotein CD11/CD18 on the of these changes. Occlusion of the superior mesenteric hepatic microvascular responses to gut I/R. Methods: Leukocyte accumulation, number of nonperfused sinuartery (SMA) for 45-60 minutes followed by reperfusion soids, and autofluorescence of reduced nicotinamide affects the liver by altering the mitochondrial redox state, adenine dinucleotide (NADH) were monitored using inincreasing tissue oxidized glutathione levels and albumin travital videomicroscopy both before and after gut I/R. extravasation, and reducing bile flow. 6-8 These liver re-Results: The number of adherent leukocytes in both sponses to gut I/R are significantly blunted in rats renmidzonal and pericentral regions after gut I/R was eledered neutropenic by pretreatment with vinblastine sulvated. Autofluorescence of NADH increased after reperfate. 9 Although these observations support a role for fusion (indicating hypoxia), particularly in the pericenneutrophils in the liver injury observed after gut I/R, very tral region. Neutrophil depletion or antibodies to either little is known about the temporal and spatial features of
A Method to Detect Remote Organ Injury after Intestinal Ischemia-Reperfusion in Mice
Nihon Kyukyu Igakukai Zasshi, 2002
Intestinal ischemia and hypoperfusion appear to play key roles in the pathogenesis of multiple organ dysfunction syndrome (MODS). While various animal models have been used to elucidate what causes MODS, investigators have recently started to use mice since knockout and transgenic technologies emerged. However, definite methods to estimate systemic organ damage, especially endothelial injury, have not well been established in mice. We, therefore, attempted to establish simple methods that enable us to detect intestinal, pulmonary, and hepatic injury in a murine model of intestinal ischemiareperfusion (I/R). Adult female BALB/c mice underwent 45 minutes of superior mesenteric artery occlusion and subcutaneously received 3ml of saline as fluid resuscitation. Two and 6 hours after reperfusion, whole blood was drawn from the inferior vena cava and the heart. Microvascular permeability and edema formation in the intestine, lung, and liver, were quantitated by Evans blue method (EB) and wet/dry ratio (W/D), respectively. Liver function was also measured by plasma alanine aminotransferase (ALT) and total bilirubin (T-Bil) concentrations. In the second set of experiments, the same methods were employed in C57BL/6 mice after 45 minutes of intestinal ischemia and 2 hours reperfusion. In BALB/c mice, intestinal injury was detected by EB and W/D and increased pulmonary permeability was measured by EB. Liver injury was quantitated by EB, W/D, and T-Bil. In C57BL/6 mice, intestinal injury was estimated by EB and W/D, lung leak by EB, and liver injury by W/D, ALT, and T-Bil. While slight difference was observed between those two strains of mice, the data indicate that intestinal, pulmonary and hepatic injury could be successfully estimated by the combination of EB, W/D, ALT and T-Bil in a murine model of intestinal I/R. These methods may become useful in mice not only to delineate the mechanisms linking intestinal I/R and remote organ injury but also in other fields of shock research.
Histology and histopathology, 2010
The prevailing notion is that ischemia reperfusion injury of the small bowel induces transient changes that resolve within a few days post-occurrence. However, chronic injury has been described following a single ischemia reperfusion in the kidney. We proceeded to ascertain if a similar outcome is also witnessed in the small bowel. ACI rats (n=32) underwent 1, 2 or 3 episodes of ischemia reperfusion by clamping the superior mesenteric artery for 45 minutes at 7-day intervals. Control groups included sham-operated (n=6) or non-operated (n=5) rats. Morphology was examined at day ninety post-ischemia reperfusion and immunostaining was used to evaluate macrophage infiltration, microvascular distribution, and apoptosis. RT-PCR was used to evaluate expression of Inter-Cellular Adhesion Molecule-1 (ICAM-1), transforming growth factor-beta (TGF-beta), Insulin Growth Factor-I (IGF-1), and Insulin Growth Factor-I Receptor (IGF-R). Intestinal function was evaluated by D-xylose performed 24 hou...
Clinical hemorheology and microcirculation, 2018
Intestinal ischemia-reperfusion (I/R) is a potentially life-threatening situation and its pathomechanism is not fully understood yet. To investigate the early micro-rheological, microcirculatory and morphological consequences of intestinal I/R in a rat model. CD rats were anesthetized and subjected to Control (n = 7) or I/R (n = 7) groups. Left femoral artery cannulation and median laparotomy were performed. In the I/R group the superior mesenteric artery was clamped for 30 minutes. Blood samples were taken before (Base) and after the ischemia, at the 30th, 60th and 120th minutes of the reperfusion (R-30, R-60, R-120). Hematological parameters, erythrocyte deformability and aggregation were determined. On the jejunum, the liver and the right kidney laser Doppler flowmetry tests were completed. At the end of experiment histological samples were taken. Hematocrit, leukocyte and platelet counts increased during the reperfusion. Erythrocyte deformability worsened versus Control. All ery...
PLoS ONE, 2008
Background: Intestinal ischemia-reperfusion (IR) is a phenomenon related to physiological conditions (e.g. exercise, stress) and to pathophysiological events (e.g. acute mesenteric ischemia, aortic surgery). Although intestinal IR has been studied extensively in animals, results remain inconclusive and data on human intestinal IR are scarce. Therefore, an experimental harmless model for human intestinal IR was developed, enabling us to clarify the sequelae of human intestinal IR for the first time.
A New Model to Study Intestinal Ischemia-Reperfusion Damage in Man
Journal of Surgical Research, 2011
Background. This report describes a human in vivo ischemia reperfusion (IR) model of the small intestine. Animal models of intestinal IR are indispensable for our understanding of sequelae of IR induced organ damage. However, a functional experimental IR model of the human small intestine, allowing for translational research, can be considered critical for our pathophysiologic understanding of intestinal IR in man. Materials and Methods. Patients with a healthy gut undergoing abdominal surgery with a Roux-Y or similar reconstruction were included, creating the opportunity to study IR of an isolated jejunal segment in a harmless model. Results. Ischemia was induced by nontraumatic vascular clamping followed by reperfusion. This model can be adapted using variable ischemia and reperfusion times. Similarly, tissue and plasma can be collected at any given time point during ischemia until end of reperfusion, only determined by progress of the original, intended surgical procedure. Conclusion. A unique and harmless human IR model of the jejunum was created, which enables the study of acute damage to the epithelial lining and its subsequent repair mechanisms.
BioMed Research International, 2014
Mesenteric ischemia-reperfusion (IR) is associated with impairment of the gut barrier function and the initiation of a proinflammatory cascade with life-threatening results. Therefore methods directed to ameliorate IR injury are of great importance. We aimed at describing the effects of postconditioning (PC) on the alterations of the intestinal mucosal function and the inflammatory response upon mesenteric IR.Methods. Male Wistar rats were gavaged with green fluorescent protein-expressingE. colisuspensions. Animals were randomized into three groups (n=15), sham-operated, IR-, and PC-groups, and underwent 60 minutes of superior mesenteric artery occlusion, followed by 6 hours of reperfusion. Postconditioning was performed at the onset of reperfusion. Blood and tissue samples were taken at the end of reperfusion, for histological, bacteriological, and plasma examinations.Results. The PC-group presented a more favorable claudin-2, claudin-3, claudin-4, and zonula occludens-1 membrane e...