• William M Armstead, J Willis Kiessling, W Andrew Kofke, and Monica S Vavilala.
• Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, USA. armsteaw@uphs.upenn.edu
• Crit. Care Med. 2010 Sep 1;38(9):1868-74.

ObjectiveTraumatic brain injury contributes to morbidity and mortality in children and boys are disproportionately represented. Hypotension is common and worsens outcome after traumatic brain injury. Extracellular signal-related kinase mitogen-activated protein kinase is upregulated and reduces cerebral blood flow after fluid percussion brain injury in piglets. We hypothesized that increased cerebral perfusion pressure through phenylephrine sex dependently reduces impairment of cerebral autoregulation during hypotension after fluid percussion brain injury through modulation of extracellular signal-related kinase mitogen-activated protein kinase.DesignProspective, randomized animal study.SettingUniversity laboratory.SubjectsNewborn (1- to 5-day-old) pigs.InterventionsCerebral blood flow, pial artery diameter, intracranial pressure, and autoregulatory index were determined before and after fluid percussion brain injury in untreated, preinjury, and postinjury phenylephrine (1 microg/kg/min intravenously) treated male and female pigs during normotension and hemorrhagic hypotension. Cerebrospinal fluid extracellular signal-related kinase mitogen-activated protein kinase was determined by enzyme-linked immunosorbent assay.Measurements And Main ResultsReductions in pial artery diameter, cerebral blood flow, cerebral perfusion pressure, and elevated intracranial pressure after fluid percussion brain injury were greater in males, which were blunted by phenylephrine pre- or postfluid percussion brain injury. During hypotension and fluid percussion brain injury, pial artery dilation was impaired more in males. Phenylephrine decreased impairment of hypotensive pial artery dilation after fluid percussion brain injury in females, but paradoxically caused vasoconstriction after fluid percussion brain injury in males. Papaverine-induced pial artery vasodilation was unchanged by fluid percussion brain injury and phenylephrine. Cerebral blood flow, cerebral perfusion pressure, and autoregulatory index decreased markedly during hypotension and fluid percussion brain injury in males but less in females. Phenylephrine prevented reductions in cerebral blood flow, cerebral perfusion pressure, and autoregulatory index during hypotension in females but increased reductions in males. Cerebrospinal fluid extracellular signal-related kinase mitogen-activated protein kinase was increased more in males than females after fluid percussion brain injury. Phenylephrine blunted extracellular signal-related kinase mitogen-activated protein kinase upregulation in females but increased extracellular signal-related kinase mitogen-activated protein kinase upregulation in males after fluid percussion brain injury.ConclusionsThese data indicate that elevation of cerebral perfusion pressure with phenylephrine sex dependently prevents impairment of cerebral autoregulation during hypotension after fluid percussion brain injury through modulation of extracellular signal-related kinase mitogen-activated protein kinase. These data suggest the potential role for sex-dependent mechanisms in cerebral autoregulation after pediatric traumatic brain injury.

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