GUT AND LIVER - THE ORGANS RESPONSIBLE FOR INCREASED NITRIC-OXIDE PRODUCTION AFTER TRAUMA-HEMORRHAGE AND RESUSCITATION

Objective: To determine which organs produce the increased levels of n itric oxide (NO) seen after hemorrhage and resuscitation. Animals and Interventions: Adult male rats underwent laparotomy (ie, trauma induce d) and were bled to and maintained at a mean arterial pressure of 40 m m Hg until 40% of the maximum bleedout volume was returned in the form of Ringer lactate. The rats were then resuscitated with Ringer lactat e, 4 times the maximum bleedout volume for 1 hour. Sham-operated anima ls underwent only the surgical procedure. Main Outcome Measures: Plasm a levels of nitrate/ nitrite (NO3-/NO2-, stable products of NO) were m easured by colorimetric assay at the maximum bleedout volume; at the e nd of hemorrhage; at the end of resuscitation; and 1.5, 4, 8, and 24 h ours after resuscitation. In additional rats, the heart, liver, small intestine, kidneys, and spleen were harvested 4 hours after resuscitat ion for the measurement of NO3-/NO2- levels. Moreover, tissue per fusi on was determined in the above-mentioned organs by radioactive microsp heres 4 hours after resuscitation in other groups of animals. Results: Plasma levels of NO3-/NO2- were similar to those of sham-operated ani mals during hemorrhage and at the end of resuscitation. One and a half hours after the end of resuscitation, however, NO production increase d significantly. The peak levels of plasma NO3-/NO2- occurred at 4 hou rs, and the levels remained elevated even 24 hours after resuscitation . Tissue NO3-/NO2- levels were significantly increased in the liver, s mall intestine, and spleen 4 hours after resuscitation. In contrast, t he levels of NO3-/ NO2- were similar to those of sham-operated animals in the heart and kidneys at all times. Blood flow in the heart was ma intained after hemorrhage, whereas hepatic, intestinal, splenic, and r enal perfusion decreased significantly. Conclusions: The gut and liver seem to be the sites responsible for the increased NO production seen after trauma and hemorrhage. The overproduction of NO is most likely caused by up-regulation of inducible NO synthase. Thus, attempts to re duce NO production using specific inhibitors for inducible NO synthase might be helpful for improving hepatic and intestinal functions after trauma and hemorrhagic shock.