Histamine does not mediate mucosal permeability changes after subclinical intestinal ischemia-reperfusion injury.
Subclinical intestinal ischemia-reperfusion injury (IRI) increases mucosal permeability, and may be an important mechanism in the etiology of necrotizing enterocolitis. The current study was designed to assess the role of histamine in mediating this phenomenon. Six-week-old rats underwent 10-minute superior mesenteric artery occlusion (SMAO) or sham operation, and ileal mucosal permeability to 51Cr EDTA was measured 30 minutes after reperfusion. Rats were pretreated with intravenous saline, mepyramine (6 mg/kg), or ranitidine (5 mg/kg). SMAO resulted in a significant increase in permeability compared to sham, which was not attenuated by either of the histamine antagonists. In a second experiment, mucosal permeability to 51Cr EDTA was measured in 6-week-old rats during aortic infusion of saline or histamine (0.5 mg/kg/min). There was no significant increase in permeability as a result of histamine infusion. In a third experiment, 6-week-old and 10-day-old rats underwent sham or 10-minute SMAO, and both portal vein and ileal tissue histamine levels were measured 30 minutes after reperfusion. There was no significant difference between sham and SMAO with respect to portal vein histamine or tissue histamine at either age.


CONCLUSIONS
(1) increased permeability was not blocked by either H1 or H2 blockers; (2) histamine infusion did not increase permeability; and (3) SMAO did not increase portal vein or tissue histamine levels. These data suggest that histamine does not play a role in mediating the increase in permeability after subclinical IRI in this model.
Langer
J C
JC
Intestinal Disease Research Unit, McMaster University, Hamilton, Ontario.
Sohal
S S
SS
Marshall
J
J
D000818:Animals; D002860:Chromium Radioisotopes; D004492:Edetic Acid; D004761:Enterocolitis, Pseudomembranous / Q000209:etiology; D006632:Histamine / Q000378:metabolism / Q000502:physiology*; D007082:Ileum / Q000503:physiopathology; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011738:Pyrilamine / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D014886:Weaning
D002860:Chromium Radioisotopes; D006632:Histamine; D011899:Ranitidine; D004492:Edetic Acid; D011738:Pyrilamine