title: Transplantation of preconditioned intestinal grafts is associated with lower inflammatory activation and remote organ injury in rats.
abstract: Reperfused grafts--particularly the intestine--release free radicals and cytokines into the systemic circulation. The type of discharge, which is greatly dependent on the local injury, may also induce inflammatory activation in distant organs and leading to multiple system and organ failure. It has been suggested that intestinal grafts from tacrolimus (TRL)-pretreated donors show improved morphology and microcirculation. We studied whether transplantation of intestines from TRL-pretreated donors influenced inflammatory response and remote organ injury posttransplantation. Donor Sprague Dawley rats received TRL or saline (controls) intravenously at 6 hours prior to graft harvest. The intestinal grafts were preserved in saline for 3 hours before transplantation. At 6 and 12 hours postreperfusion hepatic and renal cortical microcirculation were assessed using laser-Doppler flowmetry (n = 8-12 per group). Blood pressure was measured; liver, kidney, and serum samples were obtained. We analyzed hepatic and renal ICAM-1 expression and caspase-3-like activity as well as plasma content of tumor necrosis factor-alpha and interleukin-6. Pretreated graft recipients had higher mean arterial pressure (82 +/- 10 vs 51 +/- 17 mm Hg, P < .05) and renal perfusion at 6 hours whereas liver perfusion was similar at both 6 and 12 hours. Liver and renal functions were also superior among recipients of pretreated grafts. Both caspase-3-like activity and ICAM-1 expression in liver and kidney were lower in pretreated graft recipients. Plasma IL-6 levels were lower in animals receiving pretreated grafts. Transplantation of intestines from TRL-pretreated donors was followed by a lower systemic inflammatory response, improved organ function and decreased remote injury early posttransplantation compared with animals receiving grafts from untreated donors.
authors.affiliation: Department of Surgery and Transplantation, Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, 413-45 Göteborg, Sweden. mihai.oltean@wlab.gu.se
authors.forename: M
authors.initials: M
authors.lastname: Oltean
authors.forename: S
authors.initials: S
authors.lastname: Mera
authors.forename: R
authors.initials: R
authors.lastname: Olofsson
authors.forename: C
authors.initials: C
authors.lastname: Zhu
authors.forename: K
authors.initials: K
authors.lastname: Blomgren
authors.forename: E
authors.initials: E
authors.lastname: Hallberg
authors.forename: M
authors.initials: M
authors.lastname: Olausson
mesh_terms: D000818:Animals; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000453:epidemiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007422:Intestines / Q000637:transplantation*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000502:physiology*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008833:Microcirculation; D023421:Models, Animal; D011183:Postoperative Complications / Q000145:classification; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning; D014185:Transplantation, Isogeneic / Q000009:adverse effects; D014947:Wounds and Injuries / Q000453:epidemiology
chemical_list: D007166:Immunosuppressive Agents; D018799:Intercellular Adhesion Molecule-1; D016559:Tacrolimus