Cerebral hemodynamic effects of phenylephrine and l-arginine after cortical impact injury

Objective: To determine the effects of a presser agent (phenylephrine and L -arginine) on the abnormal cerebral hemodynamics and on neurologic outcome after a severe cortical impact injury in rats. Design:Prospective, randomized study. Setting: University laboratory. Subjects: Male Long-Evans rats, weighing 300 to 400 g, fasted overnight. Interventions: The animals were anesthetized with isoflurane, and a severe cortical impact injury (velocity, 5 m/sec; deformation, 3 mm) was produced in the right parietal cortex. Five minutes after impact injury, one of the following three treatments were infused: 1 mL saline intravenously for 10 m ins, 300 mg/kg L-arginine in 1 mL saline intravenously for 10 mins, or 0.3 mu g/kg/min phenylephrine intravenously for 3 hrs, Mean arterial pressure, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and laser D oppler flow (IDF) at the impact site and in the contralateral parietal cort ex were monitored for 3 hrs after the impact injury. Histologic examination of the brain was performed at 2 wks after injury in a separate group of L- arginine- and saline-treated animals. Measurements and Main Results: The immediate response to the impact injury was an increase in ICP, and a decrease in mean arterial pressure, CPP, and LDF, In the saline-treated animals, LDF decreased to <25% of the baseline v alues at the impact site and stayed at that level for the entire 3-hr monit oring period. On the contralateral side, LDF decreased initially and recove red gradually to approximately 50% of the preimpact baseline value. Infusio n of both phenylephrine and L-arginine increased LDF back to near-baseline levels. However, phenylephrine increased ICP significantly, whereas ICP wit h L-arginine did not change. L-arginine treatment reduced the contusion vol ume from a median value of 5.28 mm(3) to 0.63 mm(3). Conclusions: Phenylephrine increased cerebral blood flow (CBF) by increasin g CPP, L-arginine, however, increased CBF without changing CPP, The improve ment in CBF was accompanied by a decrease in neurologic injury. Although th e presser agents are used currently to increase CBF after traumatic brain i njury, other strategies may also increase CBF without the potential adverse effects of induced hypertension.