Intracranial pressure reduction by a central alpha-2 adrenoreceptor agonist after subarachnoid hemorrhage

Pharmacological manipulation of cerebral venous blood volume is a theoretical approach to reduce elevated intracranial pressure (ICP). Microapplication of alpha-2 adrenoreceptor agonists has been shown to constrict pial veins selectively. This report explores the physiological effects of the intravenous alpha-2 agonist xylazine in a canine model of raised ICP after subarachnoid hemorrhage (mean arterial pressure, heart rate, and ICP were measured and compared in five groups: normal saline [n = 4], xylazine [0.05-1.00 mg/kg] [n = 28], tolazoline [a semiselective alpha-2 antagonist, 5 mg/kg] [n = 6], tolazoline [5 mg/kg] plus xylazine [1.0 mg/kg] [n = 7], and phenylephrine [0.008 mg/kg], a selective alpha-1 agonist [n = 3]). Treatment with xylazine produced a significant (P < 0.01), transient, dose-dependent reduction in ICP that was blocked by pretreatment with tolazoline. Treatment with tolazoline alone produced significant (P < 0.01) increases in ICP and mean arterial pressure. Treatment with phenylephrine produced significant (P < 0.01) increases in mean arterial pressure but had no affect on ICP. These results raise the possibility of using an alpha-2 adrenoreceptor agonist for the treatment of elevated ICP after brain injury.