Hypothermia protects against gut ischemia/reperfusion-induced impaired intestinal transit by inducing heme oxygenase-1.
OBJECTIVE
Gut ischemia/reperfusion (I/R) elicits an inflammatory response that impairs intestinal transit. We have previously shown that regional intraischemic hypothermia (IH) protects against moderate gut I/R-induced mucosal injury, is associated with decreased NF-kappaB activity and inducible nitric oxide synthase induction and preserves heme oxygenase-1 (HO-1) expression. HO-1 provides cytoprotection in various models of oxidant stress. We, therefore, tested the hypothesis that IH protects against gut I/R-induced impaired intestinal transit via HO-1 induction.


METHODS
At laparotomy (lap), Sprague-Dawley rats had duodenal catheters placed followed by sham or gut I/R (superior mesenteric artery occlusion for 75 min) with or without regional IH (15 degrees C). Each animal was placed on a heating blanket maintaining systemic normothermia (37 degrees C). At 12 or 24 h of reperfusion, small intestinal transit was determined by quantitating the distribution of a tracer (FITC dextran) in the intestine 30 min after instillation (expressed as geometric center of distribution). Ileal samples were obtained for histology and HO-1 expression, assessed by Western immunoblot at 12 and 24 h of reperfusion. In separate experiments, rats were pretreated with an HO-1 inhibitor Sn protoporphyrin IX (25 mumol/kg, ip), 1 h before superior mesenteric artery occlusion and transit measured as above.


RESULTS
Rats treated with I/R had increased histological injury and impaired intestinal transit at both 12 and 24 h compared with sham. Rats treated with I/R+IH exhibited histological injury and transit comparable with sham controls. I/R induced HO-1 expression at 12 and 24 h of reperfusion and IH augmented this I/R-induced HO-1 expression. Sn protoporphyrin IX abrogated IH protection against histological injury and impaired transit.


CONCLUSIONS
We conclude that intraischemic regional hypothermia protects against histological injury and impaired intestinal transit caused by severe gut I/R injury. Hypothermic protection under these conditions is in part due to HO-1 expression.
Department of Surgery, Trauma Research Center, University of Texas-Houston Medical School, Houston, Texas, USA.
Bashir O
BO
Attuwaybi
Heitham T
HT
Hassoun
Lei
L
Zou
Rosemary A
RA
Kozar
Bruce C
BC
Kone
Norman W
NW
Weisbrodt
Frederick A
FA
Moore
D000818:Animals; D015153:Blotting, Western; D003250:Constriction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005772:Gastrointestinal Transit; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051547:Heme Oxygenase-1; D007036:Hypothermia, Induced; D007082:Ileum / Q000201:enzymology / Q000473:pathology; D007421:Intestine, Small / Q000503:physiopathology; D007422:Intestines / Q000098:blood supply*; D008297:Male; D017538:Mesenteric Artery, Superior; D008665:Metalloporphyrins / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1