L-ARGININE RESTORES THE DEPRESSED CARDIAC-OUTPUT AND REGIONAL PERFUSION AFTER TRAUMA-HEMORRHAGE

Background. Previous studies indicate that vascular endothelial cell d ysfunction occurs early after trauma-hemorrhage and may contribute to further alterations in tissue perfusion and cellular function. Because endothelial cell dysfunction is characterized by the reduced release of nitric oxide (NO) by endothelial constitutive NO synthase (cNOS), w e tested the hypothesis that administration of L-arginine (ie, the sub strate for cNOS) after trauma and hemorrhage should have beneficial ef fects on depressed cardiac output and organ blood flow under those con ditions. Methods. Rats underwent a laparotomy (ie, trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg u ntil 40 % of maximal shed blood volume was returned in the form of Rin ger's lactate solution. The animals were then resuscitated with 4 time s the volume of the shed blood in the form of Ringer's lactate solutio n over 1 hour L-arginine (300 mg/kg body wt) or saline solution was in fused intravenously during the first 15 minutes of resuscitation. Card iac output and organ blood flow were determined by Sr-85-microspheres at 1.5 and 4 hours after the completion of resuscitation. Plasma inter leukin-G (IL-6) was determined by bioassay at 4 hours after resuscitat ion. Results. Cardiac output and bloodflow in the kidneys, small intes tine, and lungs decreased significantly after hemorrhage and resuscita tion. In addition, portal bloodflow and total hepatic perfusion were a lso significantly reduced. Administration of L-arginine at the onset o f fluid resuscitation, however, restored the depressed cardiac output and tissue perfusion. Moreover, the up-regulated plasma levels of IL-6 were also attenuated by L-arginine administration. Conclusions, Becau se the adjuvant we of L-arginine restored the depressed cardiac output and organ blood flow and decreased plasma levels of lL-6, administrat ion of this essential amino acid should be considered as a useful adju nct to fluid resuscitation for improving cardiovascular function in tr auma victims.