title: Differential concentration-dependent effects of prolonged norepinephrine infusion on intraparenchymal hemorrhage and cortical contusion in brain-injured rats.
abstract: Under clinical conditions catecholamines are infused to elevate cerebral perfusion pressure and improve impaired posttraumatic cerebral microcirculation. This, however, is associated with the risk of additional hemorrhage in the acute phase following traumatic brain injury. In the present study we investigated the dose-dependent effects of prolonged norepinephrine infusion on arterial blood pressure, blood glucose, and structural damage in brain-injured rats. At 4 h following induction of a focal cortical contusion (CCI), 40 rats were randomized to receive low (0.15), medium (0.3), or high dose (1 microg/kg/min) norepinephrine. Control rats were given equal volume of NaCl. Norepinephrine and NaCl were infused intravenously via Alzet osmotic pumps for 44 h. Mean arterial blood pressure (MABP), blood gases and blood glucose were determined before, at 4, 24, 48 h after CCI in repeatedly anesthetized rats (n = 28). Systolic arterial blood pressure (SABP) was measured using the tail cuff method in awake, restrained rats (n = 12). Cortical contusion and intraparenchymal hemorrhage volume were quantified at 48 h in all rats. MABP determined in anesthetized rats was only marginally increased. SABP was significantly elevated during infusion of medium and high dose norepinephrine in awake rats, exceeding 140 mm Hg. Medium and high dose norepinephrine significantly increased cortical hemorrhage by 157% and 142%, without increasing the cortical contusion volume. Low dose norepinephrine significantly reduced the cortical contusion by 44%. Norepinephrine aggravates the underlying brain damage during the acute posttraumatic phase. Future studies are needed to determine the least deleterious norepinephrine concentration.
authors.affiliation: Institute of Neuropathology, Charité Campus Virchow Klinikum, Humboldt-University, 13353 Berlin, Germany. frank.van_landeghem@charite.de
authors.forename: Frank K H
authors.initials: FK
authors.lastname: Van Landeghem
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Unterberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Von Deimling
authors.forename: John F
authors.initials: JF
authors.lastname: Stover
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007262:Infusions, Intravenous; D007427:Intracranial Pressure / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage* / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013566:Sympathomimetics / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D013566:Sympathomimetics; D009638:Norepinephrine