title: Acute colonic ischaemia in rats results in long-term structural changes without alterations of colonic sensitivity.
abstract: Colonic ischaemia and mast cells have been involved in the pathophysiology of the functional gastrointestinal disorder irritable bowel syndrome, although the cause-effect relationships remain unknown. We assessed long-term histopathological and functional changes associated to an acute ischaemic episode (1 h) of the colon, followed by 8-week recovery, in rats. Functional colonic alterations [sensitivity during colorectal distension (CRD), compliance and propulsive motility] were assessed regularly during the recovery. Colonic histopathology (presence of inflammation, morphometric alterations and variations in neuronal density in the enteric nervous system) 8-week postischaemia was assessed. Following ischaemia, none of the functional parameters tested (motility, sensitivity and compliance) were affected. At necropsy, the colon presented an overall normal appearance with an increase in weight of the ischaemic area (mg/cm: 99 +/- 6; P < 0.05 vs. control: 81 +/- 4 or sham ischaemia: 81 +/- 3). Histopathological evaluations revealed the presence of a local infiltrate of mast cells in the area of ischaemia (nb of mast cells: 142 +/- 50; P < 0.05 vs. control, 31 +/- 14 or sham ischaemia: 40 +/- 16), without other significant alterations. Animals subjected to colonic ischaemia and treated 8 weeks later with the mast cell degranulator, compound 48/80, showed no changes in CRD-related pain responses. These studies show that acute colonic ischaemia is associated with the presence of a long-term local infiltration of mast cells, located within the serosa and muscle layers, despite the absence of functional changes, including colonic sensitivity. Considering the important pathophysiological functions of mast cells, the observed mast cell infiltration may be involved in ischaemia-induced functional changes yet to be characterized.
authors.affiliation: AstraZeneca R&D Mölndal, Mölndal, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ravnefjord
authors.forename: Madeleine
authors.initials: M
authors.lastname: Pettersson
authors.forename: Erika
authors.initials: E
authors.lastname: Rehnström
authors.forename: Vicente
authors.initials: V
authors.lastname: Martinez
mesh_terms: D000208:Acute Disease; D000818:Animals; D002452:Cell Count; D002465:Cell Movement; D017091:Colitis, Ischemic / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D004548:Elasticity; D005260:Female; D005769:Gastrointestinal Motility; D043183:Irritable Bowel Syndrome; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology*; D023421:Models, Animal; D009474:Neurons / Q000473:pathology; D010146:Pain / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017833:Visceral Afferents / Q000473:pathology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D003189:p-Methoxy-N-methylphenethylamine