{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:13:34Z","timestamp":1791231214761,"version":"4.1.0"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Intestinal ischemia\/reperfusion (I\/R)-injury often results in sepsis and organ failure and is of major importance in the clinic. A potential strategy to reduce I\/R-injury is the application of ischemic preconditioning (IPC) during which repeated, brief episodes of I\/R are applied. The aim of this study was to evaluate physiological and cellular effects of intestinal I\/R-injury and to compare the influence of in-vivo IPC (iIPC) with ex-vivo IPC (eIPC), in which blood derived factors and nerval regulations are excluded.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Using an established perfused rat intestine model, effects of iIPC and eIPC on physiological as well as cellular mechanisms of I\/R-injury (60 min hypoxia, 30 min reperfusion) were investigated. iIPC was applied by three reversible occlusions of the mesenteric artery in-vivo for 5 min followed by 5 min of reperfusion before isolating the small intestine, eIPC was induced by stopping the vascular perfusion ex-vivo 3 times for 5 min followed by 5 min of reperfusion after isolation of the intestine. Study groups (each N = 8\u20139 animals) were: iIPC, eIPC, I\/R (iIPC group), I\/R (eIPC group), iIPC+I\/R, eIPC+I\/R, no intervention\/control (iIPC group), no intervention\/control (eIPC group). Tissue morphology\/damage, metabolic functions, fluid shifts and barrier permeability were evaluated. Cellular mechanisms were investigated using signaling arrays.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>I\/R-injury decreased intestinal galactose uptake (iIPC group: p&lt;0.001), increased vascular perfusion pressure (iIPC group: p&lt;0.001; eIPC group: p&lt;0.01) and attenuated venous flow (iIPC group: p&lt;0.05) while lactate-to-pyruvate ratio (iIPC group, eIPC group: p&lt;0.001), luminal flow (iIPC group: p&lt;0.001; eIPC group: p&lt;0.05), goblet cell ratio (iIPC group, eIPC group: p&lt;0.001) and apoptosis (iIPC group, eIPC group: p&lt;0.05) were all increased. Application of iIPC prior to I\/R increased vascular galactose uptake (P&lt;0.05) while eIPC had no significant impact on parameters of I\/R-injury. On cellular level, I\/R-injury resulted in a reduction of the phosphorylation of several MAPK signaling molecules. Application of iIPC prior to I\/R increased phosphorylation of JNK2 and p38\u03b4 while eIPC enhanced CREB and GSK-3\u03b1\/\u03b2 phosphorylation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Intestinal I\/R-injury is associated with major physiological and cellular changes. However, the overall influence of the two different IPC strategies on the acute phase of intestinal I\/R-injury is rather limited.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0256957","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T17:43:13Z","timestamp":1630690993000},"page":"e0256957","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Effects of different ischemic preconditioning strategies on physiological and cellular mechanisms of intestinal ischemia\/reperfusion injury: Implication from an isolated perfused rat small intestine model"],"prefix":"10.1371","volume":"16","author":[{"given":"Yuk 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