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Inactivation of inducible nitric oxide synthase protects intestinal pacemaker cells from postoperative damage
Author(s) -
Yanagida Hiroe,
Sanders Kenton M.,
Ward Sean M.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.126482
Subject(s) - nitric oxide synthase , interstitial cell of cajal , nitric oxide , medicine , ileus , anastomosis , postoperative ileus , anesthesia , pathology , endocrinology , surgery , immunohistochemistry
Abdominal surgery causes postoperative gastrointestinal dysmotility which can progress to paralytic ileus. Surgery causes inflammatory responses leading to loss of interstitial cells of Cajal (ICC), which generate intestinal pacemaker activity. Here, we demonstrate that a deficiency in or pharmacological inhibition of inducible nitric oxide synthase (iNOS) before surgery protects ICC from postoperative damage. Ileal segments from wild‐type, iNOS and cyclooxygenase‐2 (COX‐2) knockout mice were resected and reconstructions were performed by end‐to‐end anastomoses. Wild‐type animals were exposed to iNOS inhibitors before surgery, and electrical activity and ICC were examined 5 h after surgery. Intestinal surgery on wild‐type mice caused a significant reduction in ICC and pacemaking at distances up to 5 cm from the anastomosis site. ICC networks and pacemaking were protected in iNOS −/− mice. In animals treated preoperatively with iNOS inhibitors, pacemaker activity was depressed only at the anastomosis site. COX‐2 deficiency also muted postoperative disruption in pacemaker activity. Postoperative surgical damage consists of a local response and a more widespread response in which ICC and pacemaker activity are disrupted. Damage to ICC and pacemaking was greatly attenuated in the absence of NO derived from iNOS. Thus, management of iNOS expression or activity prior to intestinal surgery protects against postsurgical dysmotility and reduces the severity of postoperative ileus.