title: Hypertonicity of intestinal smooth muscle as a factor of intestinal ischemia in necrotizing enterocolitis.
abstract: Necrotizing enterocolitis (NEC) is thought to be secondary to mucosal ischemia. Because blood flow to the submucosal plexus is derived from vessels traversing three separate layers of visceral smooth muscle (longitudinal, circular, and muscularis mucosa), we investigated whether an increase in their tone might elicit mucosal ischemia. The intestinal intraluminal pressure (IIP) and the superior mesenteric artery (SMA) blood flow were evaluated in 23 dogs before and after either ligation of the SMA or neostigmine infusion into the SMA. Changes in vascularity were assessed by silicone rubber casting, India ink, or arteriography. Ten minutes after ligation of the SMA, there was a considerable increase in peristalsis, IIP, and inability to fill the intestinal microcirculation by the three methods described. Mucosal necrosis was present three hours later. In the neostigmine infusion group after a transient increase in mesenteric flow, the IIP rose 750%, while the mesenteric flow fell by 40%, mucosal necrosis occurred in one hour. When myotomy was performed on the antimesenteric border, mucosal necrosis was prevented. In a third group, neostigmine infused (femoral artery) in the hind limb demonstrated vasodilating effects. The data indicate that an increase in the myogenic tone and frequency of contraction of intestinal smooth muscle can produce mucosal ischemia, thus, intestinal hypertonicity may be an important factor in the pathogenesis of intestinal ischemia and possibly NEC. The effects of neostigmine in these experiments raise questions regarding its use during anesthesia in neonates with intestinal low flow states.
mesh_terms: D000818:Animals; D004285:Dogs; D004761:Enterocolitis, Pseudomembranous / Q000209:etiology*; D006471:Gastrointestinal Hemorrhage / Q000473:pathology; D005769:Gastrointestinal Motility / Q000187:drug effects; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000473:pathology; D007421:Intestine, Small / Q000503:physiopathology; D007511:Ischemia / Q000209:etiology* / Q000503:physiopathology; D008026:Ligation; D008638:Mesenteric Arteries; D008641:Mesenteric Vascular Occlusion / Q000503:physiopathology; D009122:Muscle Hypertonia / Q000139:chemically induced / Q000150:complications*; D009130:Muscle, Smooth / Q000503:physiopathology; D009388:Neostigmine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D009388:Neostigmine