title: Mechanisms of gastrointestinal ischemia-reperfusion injury and potential therapeutic interventions: a review and its implications in the horse.
abstract: Restoration of blood flow after a period of intestinal ischemia is necessary to maintain cell function and viability; however, the reintroduction of oxygen can initiate a cascade of events that exacerbates tissue injury. Intestinal I-R injury is manifested as increased microvascular and mucosal permeability, and mucosal necrosis. Reperfusion injury begins with the accumulation of hypoxanthine from ATP metabolism and the conversion of XDH to XO during ischemia. Upon reperfusion, the XO catalyzes the conversion of hypoxanthine to superoxide radicals in the presence of oxygen. Superoxide radicals are further reduced to highly reactive hydroxyl radicals, which initiate lipid peroxidation. Lipoperoxidation causes functional and structural alterations in cell membrane lipids and can release numerous inflammatory mediators, which exacerbate tissue damage. Neutrophils are recruited into tissues during ischemia and on reperfusion; then they undergo degranulation and release destructive products (proteases and OFRs), which mediate further tissue injury. A limited number of experimental studies in the gastrointestinal tract of horses have shown I-R injury. Additional studies are necessary to further elucidate and sequence the precise pathophysiologic mechanisms occurring in the equine intestine during I-R. Therapy should be focused on prevention of I-R injury by pharmacologic or chemical inhibition or modification of these pathophysiologic pathways. Selected pharmacologic agents or drug combinations may offer novel, scientifically relevant and yet practical approaches to alleviating intestinal I-R injury in horses. This may improve survival of horses with naturally acquired intestinal strangulation obstruction.
authors.affiliation: Department of Veterinary Clinical Sciences, Ohio State University, Columbus, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Moore
authors.forename: W W
authors.initials: WW
authors.lastname: Muir
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000818:Animals; D005767:Gastrointestinal Diseases / Q000503:physiopathology / Q000628:therapy / Q000662:veterinary*; D006734:Horse Diseases / Q000503:physiopathology* / Q000628:therapy*; D006736:Horses; D015427:Reperfusion Injury / Q000503:physiopathology / Q000628:therapy / Q000662:veterinary*