In vivo effect of propranolol dose and timing on cerebral perfusion after traumatic brain injury.
BACKGROUND
In vivo models of traumatic brain injury (TBI) demonstrate increased cerebral perfusion, decreased cerebral hypoxia, reduced cerebral edema, and improved neurologic recovery with propranolol administration. The purpose of this study was to determine the effect of different propranolol doses and timing on cerebral perfusion in a murine TBI model.


METHODS
Fifteen minutes after TBI, three groups of mice (four mice per group) were randomized to receive intravenous injections of placebo, 4 mg/kg propranolol, or 1 mg/kg propranolol. Two delayed treatment groups were randomized to receive placebo or 4 mg/kg propranolol 60 minutes after TBI. Cerebral perfusion was then imaged by micropositron emission tomography.


RESULTS
With placebo injection 15 minutes after TBI, the standard uptake value (SUV) mean was 0.395 +/- 0.01; with 4 mg/kg propranolol, the SUV mean was 0.515 +/- 0.04; and with 1 mg/kg propranolol, the SUV mean was 0.46 +/- 0.01. Animals receiving 4 mg/kg propranolol demonstrated significant improvement (p < 0.01) in cerebral perfusion compared with placebo and compared with 1 mg/kg propranolol. With placebo injection at 60 minutes after TBI, the SUV mean was 0.26 +/- 0.03; and with 4 mg/kg propranolol, the SUV mean was 0.43 +/- 0.02. After 60 minutes, animals receiving 4 mg/kg propranolol demonstrated significant improvement (p < 0.01) in cerebral perfusion compared with placebo.


CONCLUSIONS
In a murine model of TBI, higher doses of propranolol were preferable to lower doses and both early and late propranolol administration improved cerebral perfusion. Potential mechanisms and therapeutic potential require further research.
Division of Trauma and Critical Care, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Eric J
EJ
Ley
Ryan
R
Park
Grant
G
Dagliyan
David
D
Palestrant
Chad M
CM
Miller
Peter S
PS
Conti
Daniel R
DR
Margulies
Ali
A
Salim
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D049268:Positron-Emission Tomography; D011433:Propranolol / Q000008:administration & dosage*; D012039:Regional Blood Flow; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D011433:Propranolol