Moderate hypothermia as a rescue therapy against intestinal ischemia and reperfusion injury in the rat.
OBJECTIVE
Moderate hypothermia is protective when applied throughout experimental intestinal ischemia and reperfusion (I/R). However, therapeutic intervention is usually possible only after ischemia has occurred. The aim of this study was to evaluate moderate hypothermia when applied at reperfusion as a rescue therapy for intestinal I/R.


METHODS
Prospective, randomized, controlled experiment.


METHODS
University research laboratory.


METHODS
Adult male Sprague-Dawley rats (240-300 g).


METHODS
In experiment I, rats underwent 60 mins of normothermic intestinal ischemia (36-38 degrees C) plus 300 mins of reperfusion at either normothermia or moderate hypothermia (30-32 degrees C) with or without rewarming. Hemodynamics were measured invasively and survival was assessed. In experiment II, rats underwent 60 mins of normothermic ischemia plus 120 mins of reperfusion at either normothermia or moderate hypothermia. At kill, organs and a blood sample were collected.


RESULTS
In experiment I, all normothermic I/R rats died within 197 mins of reperfusion after developing severe tachycardia and hypotension, whereas hypothermic rats, with or without rewarming, were alive at 300 mins of reperfusion (p < .001 vs. I/R normothermia) and were hemodynamically stable. In experiment II, normothermic reperfusion caused histologic and biochemical damage to the gut, hepatic energy failure, and inflammatory infiltration of the lung. However, hypothermia reduced injury to the reperfused ileum and prevented distant organ injury by counteracting energy failure in the liver, systemic overproduction of nitric oxide, altered cardiac fatty acid metabolism, and infiltration of inflammatory cells in the lungs.


CONCLUSIONS
Hypothermia applied as a rescue therapy for intestinal I/R abolishes mortality even after rewarming. Hypothermic protection during early reperfusion appears to be mediated by several pathways, including prevention of intestinal and pulmonary neutrophil infiltration, reduction of oxidative stress in the ileum, and preservation of cardiac and hepatic energy metabolism. Moderate hypothermia may improve outcome in clinical conditions associated with intestinal I/R.
Stefanutti
Giorgio
G
Department of Paediatric Surgery, Institute of Child Health, London, United Kingdom.
Pierro
Agostino
A
Parkinson
Emma J
EJ
Smith
Virpi V
VV
Eaton
Simon
S
D000818:Animals; D007036:Hypothermia, Induced / Q000379:methods; D007422:Intestines / Q000098:blood supply*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000628:therapy*