Effects of hypertonic arginine on cerebral blood flow and intracranial pressure after traumatic brain injury combined with hemorrhagic hypotension

Hypertonic saline solutions improve cerebral blood flow (CBF) when used for acute resuscitation from hemorrhagic hypotension accompanying some models of traumatic brain injury (TBI); however, the duration of increased CBF is brief. Because the nitric oxide synthase substrate l-arginine provides prolonged improvement in CBF after TBI, we investigated whether a hypertonic resuscitation fluid containing l-arginine would improve CBF in comparison to hypertonic saline without l-arginine in a model of moderate, paramedian, fluid-percussion TBI followed immediately by hemorrhagic hypotension (mean arterial pressure [MAP] = 60 mm Hg for 45 min). Sprague-Dawley rats were anesthetized with 4.0% isoflurane, intubated and ventilated with 1.5%-2.0% isoflurane in oxygen/air (50:50). After preparation for TBI and measurement of CBF using laser Doppler flowmetry and measurement of intracranial pressure (ICP) using an implanted transducer, rats were subjected to moderate (2.0 atm) TBI, hemorrhaged for 45 min, and randomly assigned to receive an infusion of hypertonic saline (7.5%, 2,400 mOsm total; 6 mL/kg; n = 6) or hypertonic saline with 50, 100, or 300 mg/kg l-arginine (2,400 mOsm; 6 mL/kg; n = 6 in each of the three dose groups) and then monitored for 120 min after the end of infusion. CBF was measured continuously and calculated as a percent of the pre-TBI baseline during the hemorrhage period, after reinfusion of one of the hypertonic arginine solutions, and 30, 60, and 120 min after reinfusion. All four hypertonic solutions initially improved MAP, which, by 120 min after infusion, had decreased nearly to the levels observed during hemorrhage. ICP remained below baseline levels during resuscitation in all groups, although ICP was slightly greater (P = NS) than baseline in the hypertonic saline group. CBF increased similarly in all groups during infusion and then decreased similarly in all groups. At 120 min after infusion, CBF was highest in the group infused with hypertonic saline, but the difference was not significant. We conclude that the improvement of MAP, ICP, and CBF produced by hypertonic saline alone after TBI and hemorrhagic hypotension is not significantly enhanced by the addition of l-arginine at these doses.