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.
Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
J M
JM
McCormick
P W
PW
McCormick
J M
JM
Zabramski
R F
RF
Spetzler
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007427:Intracranial Pressure / Q000187:drug effects* / Q000502:physiology; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014043:Tolazoline / Q000494:pharmacology*; D014991:Xylazine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D014991:Xylazine; D014043:Tolazoline