Direct Peritoneal Resuscitation Improves Mesenteric Perfusion by Nitric Oxide Dependent Pathways

dc.contributor.authorKhaneki, Sina
dc.contributor.authorJensen, Amanda R.
dc.contributor.authorDrucker, Natalie A.
dc.contributor.authorMarkel, Troy A.
dc.contributor.departmentDepartment of Surgery, IU School of Medicineen_US
dc.date.accessioned2017-06-08T14:11:53Z
dc.date.available2017-06-08T14:11:53Z
dc.date.issued2017-06
dc.description.abstractBackground Direct peritoneal resuscitation (DPR) has been shown to increase survival after intestinal ischemia and reperfusion injury (I/R). We have previously appreciated that minimum essential medium (MEM), a synthetic cell culture medium with bovine serum, glutamine, and antibiotics, contributes to these benefits. We hypothesized that (1) DPR using MEM as a dialysate would increase mesenteric perfusion, improve intestinal mucosal injury, and limit intestinal and hepatic inflammation after intestinal I/R and (2) these improvements would be dependent on endothelial nitric oxide pathways. Methods Eight-week-old C57Bl6J wild-type (WT) and eNOS Knock Out (eNOS KO) male mice were anesthetized and intestinal ischemia was induced for 60 min. After ischemia, 1 mL of phosphate buffered saline vehicle or MEM was injected into the abdominal cavity. Intestinal perfusion was reassessed after 48 h. Animals were then euthanized, and intestines and livers explanted for histologic and molecular analyses. Results DPR with MEM significantly improved mesenteric perfusion compared with vehicle (phosphate buffered saline) as measured by Laser Doppler Imaging (WT + MEM 91.58 ± 13.74%, WT + Vehicle 44.27 ± 11.93%, P < 0.05); however, these benefits were lost when endothelial nitric oxide signaling pathways were ablated (eNOS KO + MEM 21.72 ± 5.67 %, eNOS KO + Vehicle 45.24± 11.31%). WT mice treated with MEM also had significantly better preservation of their mucosal architecture (WT + MEM Mdn = 1.0, interquartile range [IQR] = 1.25, WT + Vehicle Mdn = 3.0, IQR = 2.0, P < 0.05). When we compared eNOS KO mice treated with either MEM or vehicle the protective effect of MEM disappeared (eNOS KO + MEM Mdn = 2.0, IQR = 2.25, eNOS KO + Vehicle Mdn = 2.0, IQR = 1.0 P > 0.05). Intestinal levels of interleukin (IL)-1β were increased in WT animals treated with MEM compared with eNOS KOs, whereas concentrations of intestinal IL-6 were similar between groups. Hepatic levels of both IL-1β and IL-6 were significantly elevated in eNOS KOs compared with WT treated with MEM. Conclusions DPR with MEM has significant therapeutic potential for improving mesenteric perfusion, intestinal injury, and the local inflammatory response after intestinal I/R. These benefits appear to be dependent on nitric oxide signaling within the endothelium.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationKhaneki, S., Jensen, A. R., Drucker, N. A., & Markel, T. A. (2017). Direct Peritoneal Resuscitation Improves Mesenteric Perfusion by Nitric Oxide Dependent Pathways. Journal of Surgical Research. http://dx.doi.org/10.1016/j.jss.2017.02.060en_US
dc.identifier.urihttps://hdl.handle.net/1805/12913
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.jss.2017.02.060en_US
dc.relation.journalJournal of Surgical Researchen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjectdirect peritoneal resuscitationen_US
dc.subjectischemia and reperfusionen_US
dc.subjectendothelial nitric oxide synthaseen_US
dc.titleDirect Peritoneal Resuscitation Improves Mesenteric Perfusion by Nitric Oxide Dependent Pathwaysen_US
dc.typeArticleen_US
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