To investigate the preventive effect of ischemic preconditioning (IPC) on ischemia/reperfusion (I/R)-induced apoptosis and injury in the rat intestine.
We divided 30 male Wistar rats, weighing 300-350 g, randomly into three groups. The control group rats (n = 10) were subjected to laparotomy only; the I/R group (n = 10) rats were subjected to occlusion of the superior mesenteric artery for 45 min, followed by reperfusion for 60 min; and the IPC group (n = 10) rats were subjected to IPC, achieved with two cycles of 5 min ischemia and 5 min reperfusion immediately before the I/R, as in the I/R group. Blood samples were collected by cardiac puncture, to measure nitrate and myeloperoxidase (MPO) levels. Histopathological and immunohistochemical studies were done to evaluate the I/R-induced apoptosis and injury.
The blood MPO and nitrate levels were increased in the I/R group, but IPC prevented their increase. There were significantly fewer apoptotic cells in the IPC group than in the I/R group, and this finding was supported by the caspase-3 expression in the ileum. The intestinal histopathology was also protected by IPC against I/R-induced injury.
Ischemic preconditioning clearly prevented I/R-induced injury and apoptosis by a mechanism related to the caspase-3-dependent pathway. We also showed that IPC inhibited leukocyte activation, with the suppression of myeloperoxidase levels in I/R and nitric oxide-related oxidoinflammatory pathway upregulation.
[Show abstract][Hide abstract] ABSTRACT: Review Intestinal ischemia/reperfusion (I/R) results in mucosal barrier impairment and enhanced bacterial translocation (BT) into systemic circulation and extraintestinal visceral organs. Such bacterial influx may lead to the develop-ment of sepsis, systemic inflammatory response syn-drome, and multiple organ failure. During ischemia, a lack of oxygen and glucose causes mitochondrial respiratory dysfunction, metabolic exhaustion, and an increase in intestinal epithelial cell death. The resultant mucosal histopathology is associated with impairment of barrier function and BT. Upon restoration of blood flow, production of free radicals from intestinal epithelial cells and mucosal phagocytes contribute to bactericidal activity; however, their prolonged activation inad-vertently aggravates morphological and functional damage to the gut. Presently, several protective strategies have been developed to correct intestinal I/R injury. These include the use of antioxidants, nitric oxide, and antileukocyte methods, as well as preventive measures, such as ischemic preconditioning and enteric supple-mentation with particular nutrients.
[Show abstract][Hide abstract] ABSTRACT: To examine the effects of adenosine and A1 receptor activation on reperfusion-induced small intestinal injury.
Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N(6)-cyclopentyladenosine, A1 receptor agonist or 8-cyclopentyl-1,3-dipropylxanthine, A1 receptor antagonist, plus adenosine before ischemia. Following reperfusion, contractions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase, malondialdehyde, and reduced glutathione levels were measured.
Ischemia significantly decreased both contraction and reduced glutathione level which were ameliorated by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolished by pretreatment with A1 receptor antagonist.
The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal injury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content.
World Journal of Gastroenterology 02/2007; 13(4):538-47. DOI:10.3748/wjg.v13.i4.538 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To test the hypotheses that repeated brief intestinal ischemic insults would elicit an intestinal preconditioning response to a subsequent intestinal I/R injury and that a similar response would be elicited by repeated lung recruitment maneuvers (RMs). Randomized experimental controlled animal study. University hospital animal laboratory. Eighteen anesthetized pigs. Animals were randomized to one of three groups, with six animals in each group. Control group 75-min superior mesenteric artery (SMA) occlusion followed by 60-min reperfusion. Ischemic preconditioning group, three 5-min-long SMA occlusions preceding 75-min SMA occlusion and 60-min reperfusion. Recruitment maneuver (RM) group, three 2-min-long RMs preceding 75-min SMA occlusion and 60-min reperfusion. We measured systemic and mesenteric hemodynamic parameters, jejunal mucosal perfusion, net mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygenation. Every 15 min, jejunal microdialysate samples were collected and analyzed for glucose, lactate, and glycerol. Jejunal tissue samples were collected postmortem. After occlusion of SMA, regional parameters in all groups indicated abolished perfusion and gradually increasing intraluminal microdialysate lactate and glycerol levels. At reperfusion, regional parameters indicated mesenteric hyperperfusion, whereas microdialysis markers of mucosal anaerobic metabolism and cell injury decreased, although not reaching baseline. Histological examination revealed severe mucosal injury in all groups. There were no significant differences between groups in the observed parameters. No protective preconditioning response could be observed when performing repeated brief intestinal ischemic insults or repeated lung RMs before an intestinal I/R injury.
Derek J Hausenloy, Luciano Candilio, Richard Evans, Cono Ariti, David P Jenkins, Shyam Kolvekar, Rosemary Knight, Gudrun Kunst, Christopher Laing, Jennifer Nicholas, John Pepper, Steven Robertson, Maria Xenou, Tim Clayton, Derek M Yellon
Patrick Meybohm, Berthold Bein, Oana Brosteanu, Jochen Cremer, Matthias Gruenewald, Christian Stoppe, Mark Coburn, Gereon Schaelte, Andreas Böning, Bernd Niemann, [...], Matthias Heringlake, Julika Schön, Michael Sander, Sascha Treskatsch, Thorsten Smul, Ewa Wolwender, Thomas Schilling, Georg Fuernau, Dirk Hasenclever, Kai Zacharowski
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