Teresa Lorenzi1, Maria Michela Cappelletti Trombettoni2, Roberto Ghiselli2, Francesca Paolinelli1, Rosaria Gesuita3, Oscar Cirioni4, Mauro Provinciali5, Wojciech Kamysz6, Elzbieta Kamysz7, Cristiano Piangatelli8, Mario Castellucci1, Mario Guerrieri2, Manrico Morroni1,9. 1. Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, School of Medicine, Università Politecnica delle MarcheItaly. 2. General Surgery and Surgery Methodology Clinic, Università Politecnica delle MarcheOspedali Riuniti, Ancona, Italy. 3. Center of Epidemiology, Biostatistics and Medical Information Technology, Università Politecnica delle MarcheItaly. 4. Clinic of Infectious Diseases, Department of Biomedical Sciences and Public Health, Università Politecnica delle MarcheOspedali Riuniti, Ancona, Italy. 5. Experimental Animal Models for Aging Units, Scientific Technological Area, I.N.R.C.A. I.R.R.C.S.Ancona, Italy. 6. Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of GdanskGdansk, Poland. 7. Department of Organic Chemistry, Faculty of Chemistry, Medical University of GdanskGdansk, Poland. 8. Division of Anesthesia and Resuscitation, Emergency DepartmentOspedali Riuniti, Ancona, Italy. 9. Electron Microscopy UnitOspedali Riuniti, Ancona, Italy.
Abstract
BACKGROUND: This study investigates the effects of the antimicrobial cationic peptide omiganan-alone and combined with the antibiotic imipenem-on colonic anastomosis healing in presence of intraperitoneal sepsis induced in a rodent model of cecal ligation and puncture (CLP). METHODS: Forty male Wistar rats were divided into 5 groups of 8 animals. Group 1 (control group) underwent laparotomy and cecal mobilization and the next day received left colon anastomosis. In group 2 (CLP without treatment), group 3 (CLP + imipenem), group 4 (CLP + omiganan), and group 5 (CLP + omiganan + imipenem), the left colon anastomosis was performed the day after CLP. Imipenem and omiganan were administered by intraperitoneal injection immediately before anastomosis construction and subsequently at 24 h intervals until the 7th postoperative day, when rats were sacrificed. Anastomotic bursting pressure was measured in situ. Tissue samples were collected for determination of hydroxyproline content and histological characteristics. RESULTS: Only rats receiving omiganan + imipenem displayed re-epithelialization, reduced neovascularization of granulation tissue, and a bursting pressure that was similar to that of controls. Omiganan-alone and combined with imipenem-was associated with a better control of inflammatory parameters than imipenem alone. In addition omiganan, like imipenem, counteracted the collagen depletion typical of sepsis. CONCLUSIONS: This experimental study demonstrates the efficacy of the new antimicrobial agent omiganan, alone and in combination with imipenem, in delaying the effects of intraperitoneal sepsis on colonic anastomosis healing and provides evidence of the value of omiganan as a therapeutic agent.
BACKGROUND: This study investigates the effects of the antimicrobial cationic peptide omiganan-alone and combined with the antibiotic imipenem-on colonic anastomosis healing in presence of intraperitoneal sepsis induced in a rodent model of cecal ligation and puncture (CLP). METHODS: Forty male Wistar rats were divided into 5 groups of 8 animals. Group 1 (control group) underwent laparotomy and cecal mobilization and the next day received left colon anastomosis. In group 2 (CLP without treatment), group 3 (CLP + imipenem), group 4 (CLP + omiganan), and group 5 (CLP + omiganan + imipenem), the left colon anastomosis was performed the day after CLP. Imipenem and omiganan were administered by intraperitoneal injection immediately before anastomosis construction and subsequently at 24 h intervals until the 7th postoperative day, when rats were sacrificed. Anastomotic bursting pressure was measured in situ. Tissue samples were collected for determination of hydroxyproline content and histological characteristics. RESULTS: Only rats receiving omiganan + imipenem displayed re-epithelialization, reduced neovascularization of granulation tissue, and a bursting pressure that was similar to that of controls. Omiganan-alone and combined with imipenem-was associated with a better control of inflammatory parameters than imipenem alone. In addition omiganan, like imipenem, counteracted the collagen depletion typical of sepsis. CONCLUSIONS: This experimental study demonstrates the efficacy of the new antimicrobial agent omiganan, alone and in combination with imipenem, in delaying the effects of intraperitoneal sepsis on colonic anastomosis healing and provides evidence of the value of omiganan as a therapeutic agent.
Entities:
Keywords:
Rat model of peritonitis; bursting pressure; colonic anastomosis; hydroxyproline concentration; omiganan; wound healing process
Authors: J J Drabick; A K Bhattacharjee; D L Hoover; G E Siber; V E Morales; L D Young; S L Brown; A S Cross Journal: Antimicrob Agents Chemother Date: 1998-03 Impact factor: 5.191