Oral CPSI-2364 Treatment Prevents Postoperative Ileus in Swine without Impairment of Anastomotic Healing
Background: Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). We demonstrated that orally applicated CPSI-2364 prevents POI in rodents by blockade of p38 MAPK pathway and abrogation of NO production in macr...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2013-11-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/356575 |
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| author | Tim O. Vilz Nils Sommer Philip Kahl Dimitrios Pantelis Joerg C. Kalff Sven Wehner |
| author_facet | Tim O. Vilz Nils Sommer Philip Kahl Dimitrios Pantelis Joerg C. Kalff Sven Wehner |
| author_sort | Tim O. Vilz |
| collection | DOAJ |
| description | Background: Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). We demonstrated that orally applicated CPSI-2364 prevents POI in rodents by blockade of p38 MAPK pathway and abrogation of NO production in macrophages. In the present experimental swine study we compared the effect of orally and intravenously administered CPSI-2364 on POI and examined CPSI-2364 effect on anastomotic healing. Methods: CPSI-2364 was administered preoperatively via oral or intravenous route. POI was induced by intestinal manipulation of the small bowel. ME specimens were examined by quantitative PCR for CCL2 chemokine gene expression and myeloperoxidase activity. Functional analyzes included measurement of ileal smooth-muscle ex vivo contractility, in vivo intestinal and colonic transit. Furthermore, anastomotic healing of a rectorectostomy after CPSI-2364 treatment was assessed by perianastomotic hydroxyproline concentration, a histochemically evaluated healing score and anastomotic bursting pressure (ABP). Results: CPSI-2364 abolished inflammation of the ME and improved postoperative smooth muscle contractility and intestinal transit independently of its application route. Hydroxyproline concentration and ABP measurement revealed no wound healing disturbances after oral or intravenous CPSI-2364 treatment whereas histological scoring demonstrated delayed anastomotic healing after intravenous treatment. Conclusion: CPSI-2364 effectively prevents POI in swine independently of its application route. Impairment of anastomotic healing could be observed after intravenous but not oral preoperative CPSI-2364 treatment. Subsumed, an oral preoperative administration of CPSI-2364 appears to be a safe and efficient strategy for prophylaxis of POI. |
| first_indexed | 2024-12-10T12:00:38Z |
| format | Article |
| id | doaj.art-2b8e83ebd1f549f6abdcccd78046ca8f |
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| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-10T12:00:38Z |
| publishDate | 2013-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-2b8e83ebd1f549f6abdcccd78046ca8f2022-12-22T01:49:37ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782013-11-013251362137310.1159/000356575356575Oral CPSI-2364 Treatment Prevents Postoperative Ileus in Swine without Impairment of Anastomotic HealingTim O. VilzNils SommerPhilip KahlDimitrios PantelisJoerg C. KalffSven WehnerBackground: Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). We demonstrated that orally applicated CPSI-2364 prevents POI in rodents by blockade of p38 MAPK pathway and abrogation of NO production in macrophages. In the present experimental swine study we compared the effect of orally and intravenously administered CPSI-2364 on POI and examined CPSI-2364 effect on anastomotic healing. Methods: CPSI-2364 was administered preoperatively via oral or intravenous route. POI was induced by intestinal manipulation of the small bowel. ME specimens were examined by quantitative PCR for CCL2 chemokine gene expression and myeloperoxidase activity. Functional analyzes included measurement of ileal smooth-muscle ex vivo contractility, in vivo intestinal and colonic transit. Furthermore, anastomotic healing of a rectorectostomy after CPSI-2364 treatment was assessed by perianastomotic hydroxyproline concentration, a histochemically evaluated healing score and anastomotic bursting pressure (ABP). Results: CPSI-2364 abolished inflammation of the ME and improved postoperative smooth muscle contractility and intestinal transit independently of its application route. Hydroxyproline concentration and ABP measurement revealed no wound healing disturbances after oral or intravenous CPSI-2364 treatment whereas histological scoring demonstrated delayed anastomotic healing after intravenous treatment. Conclusion: CPSI-2364 effectively prevents POI in swine independently of its application route. Impairment of anastomotic healing could be observed after intravenous but not oral preoperative CPSI-2364 treatment. Subsumed, an oral preoperative administration of CPSI-2364 appears to be a safe and efficient strategy for prophylaxis of POI.http://www.karger.com/Article/FullText/356575Postoperative ileusMuscularis externaIntestinal inflammationAnastomotic healing |
| spellingShingle | Tim O. Vilz Nils Sommer Philip Kahl Dimitrios Pantelis Joerg C. Kalff Sven Wehner Oral CPSI-2364 Treatment Prevents Postoperative Ileus in Swine without Impairment of Anastomotic Healing Cellular Physiology and Biochemistry Postoperative ileus Muscularis externa Intestinal inflammation Anastomotic healing |
| title | Oral CPSI-2364 Treatment Prevents Postoperative Ileus in Swine without Impairment of Anastomotic Healing |
| title_full | Oral CPSI-2364 Treatment Prevents Postoperative Ileus in Swine without Impairment of Anastomotic Healing |
| title_fullStr | Oral CPSI-2364 Treatment Prevents Postoperative Ileus in Swine without Impairment of Anastomotic Healing |
| title_full_unstemmed | Oral CPSI-2364 Treatment Prevents Postoperative Ileus in Swine without Impairment of Anastomotic Healing |
| title_short | Oral CPSI-2364 Treatment Prevents Postoperative Ileus in Swine without Impairment of Anastomotic Healing |
| title_sort | oral cpsi 2364 treatment prevents postoperative ileus in swine without impairment of anastomotic healing |
| topic | Postoperative ileus Muscularis externa Intestinal inflammation Anastomotic healing |
| url | http://www.karger.com/Article/FullText/356575 |
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