This study was designed to determine the effects of various
resuscitation fluids on intestinal
injuries after
hemorrhagic shock and
resuscitation (HS/R) and to determine the potential mechanisms. We induced HS by
bleeding male Sprague-Dawley rats to a blood pressure of 30 to 40 mmHg for 60 min. Sixty minutes later, the rats were killed (HS group) or immediately resuscitated with L-isomer
lactated Ringer's solution (HS + LR group), shed blood (HS + BL group), or hydroxyethyl
starch (HS + HES group) to maintain the blood pressure to the original value during the 60-min
resuscitation period. Three hour after
resuscitation, bacterial translocation (BT), intestinal permeability, ileal levels of
tumor necrosis factor (
TNF)-alpha,
interleukin (IL)-6,
malondialdehyde (MDA), oxidized and
reduced glutathione (GSH and
GSSG),
myeloperoxidase (MPO) activity, nuclear factor (
NF)-kappaB, activator
protein (AP)-1 activation, and ileal microscopic and ultrastructural histological changes were measured. Another experiment was designed for survival study of 24 h.
HES 130/0.4 solution was as effective as shed blood, required a small volume requirement to restore circulation, and significantly reduced HS/R-induced ileal villous morphological
injuries with an anti-inflammatory effect, as reflected by a reduction of
TNF-alpha,
IL-6, MPO activity, and
NF-kappaB activation. In addition, HES
resuscitation also reduced intestinal permeability and BT and caused less oxidative stress as reflected by a reduction of MDA,
GSSG/GSH and
AP-1 activation along with restored GSH, whereas shed blood couldn't. No significant difference was observed in outcome among groups.
HES 130/0.4 resuscitation prevents HS/R induced intestinal injury by modulating inflammatory response and preventing oxidative stress in a rat model of
hemorrhagic shock. These physiological protective effects appear to be mediated by down-regulation of the
transcription factor NF-kappaB and
AP-1.