Effects of hemodilution on long-term survival in an uncontrolled hemorrhagic shock model in rats.

Prehospital guidelines for the treatment of penetrating trauma recommend rapid volume resuscitation to normal blood pressure. There is evidence, however, that fluid resuscitation to normal blood pressure in the setting of uncontrolled hemorrhagic shock (UHS) causes increased bleeding, hemodilution, and mortality. To test this hypothesis, we evaluated the effects of blood pressure and hemodilution on survival in a rat model of UHS. UHS was produced in rats by preliminary bleed of 3 mL/100 g followed by a 75% tail amputation. Experimental design consisted of three phases: a prehospital phase, with uncontrolled bleeding and resuscitation to either 40 or 80 mm Hg with lactated Ringer's solution (LR) or lactated Ringer's solution and whole blood (WB); followed by a hospital phase, with control of the bleeding and continued resuscitation to mean arterial pressure (MAP) > 80 mm Hg and hematocrit near 30%; followed by a 3-day observation phase. There were four treatment groups, n = 8 in each group: group I, MAP = 80 mm Hg with LR only; group II, MAP = 80 mm Hg with WB and LR; group III, MAP = 40 mm Hg with LR only; and group IV, MAP = 40 mm Hg with WB and LR. All group I rats died within 2.5 hours. There were no significant differences in survival among groups II, III, and IV. Base deficit, arterial pH, and lactate levels were significantly worse in the rats resuscitated to a MAP of 80 mm Hg with LR (group I). The effects of blood pressure alone, hemodilution alone, and their interaction were significantly related to base deficit and arterial pH. Hemodilution, but not blood pressure as an end point in resuscitation, was significantly related to lactate levels. The high mortality in this model of uncontrolled hemorrhage was attributable to the effects of blood pressure, hemodilution, and the interaction between the two variables, rather than simply continued blood loss from increased hydrostatic pressure.

Inhibition of nitric oxide synthase during hemorrhagic shock increases hepatic injury.

The function of nitric oxide (NO) in hemorrhagic shock is controversial. Increased NO synthesis has been temporally correlated with severe shock and has been associated with vascular hyporeactivity to vasoconstrictor agents in isolated vascular rings. Its role in local tissue perfusion, however, is unknown. We studied the role of NO in shock-induced hepatic injury in a rodent model of decompensated hemorrhagic shock by inhibiting its synthesis with Nw-nitro-L-arginine methyl ester (L-NAME). L-NAME infusion (5 micrograms/kg/min) increased the shock-induced hepatic injury and this effect was reversible with L-arginine. L-NAME had only transient effects on systemic mean arterial blood pressure, which quickly returned to pre-L-NAME levels. We conclude that NO synthesis serves a protective function in preventing shock-induced hepatic injury and we postulate that this effect may be due to modulation of the local hepatic circulation.