title: Hypertonic saline worsens infarct volume after transient focal ischemia in rats.
abstract: OBJECTIVE
  Hypertonic saline (HS) has been advocated as a hyperosmolar agent for the treatment of cerebral edema, especially after traumatic brain injury. We tested the hypothesis that continuous intravenous HS administered during reperfusion from transient focal cerebral ischemia attenuates infarct volume.
  
  
  METHODS
  Halothane-anesthetized male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. At the onset of reperfusion, rats received a 10-mL/kg intravenous bolus of 0.9% saline (SAL, n=8) or 7.5% SAL (chloride:acetate 50:50, n=8) followed by a continuous infusion for 22 hours. In a second series of experiments, ischemic damage was determined in cohorts treated with equivolumetric 3% saline (n=8) or 20% mannitol (n=8). In a third series, regional cerebral blood flow was measured ([(14)C]iodoantipyrine autoradiography) at 6 hours of reperfusion in 7.5%-SAL-treated (n=5) or SAL-treated (n=5) animals.
  
  
  RESULTS
  In SAL rats, serum Na(+) was 137+/-3 and 138+/-2 mEq/L (mean+/-SEM) at baseline and 22 hours of reperfusion, respectively. In 7.5% SAL, serum Na(+) was 136+/-2 and 154+/-2 mEq/L at baseline and reperfusion, respectively. Physiological variables and reduction in laser-Doppler signal during MCAO and early reperfusion were not different between the 2 treatment groups. Cortical infarct volume was larger in 7.5%-SAL-treated rats (121+/-14 mm(3); 30+/-3% of contralateral cortex; P<0.05) than in SAL (64+/-15 mm(3); 16+/-4% of contralateral cortex). Striatal infarct volume was unchanged by HS therapy. Ipsilateral cortical tissue volume was increased relative to the contralateral side (by 26+/-5% with SAL; by 41+/-5% with 7.5% SAL). In contrast, ischemic damage was unaffected by 3%-SAL or 20%-mannitol treatment compared with SAL. Regional cerebral blood flow during reperfusion was heterogeneous in all animals, but there was no evidence of postischemic hypoperfusion or blood flow maldistribution in 7.5%-SAL-treated animals.
  
  
  CONCLUSIONS
  These data demonstrate that hypernatremia resulting from postischemic HS infusion worsens cortical infarct volume in transient focal cerebral ischemia. The deleterious effect is not linked to exacerbation of delayed hypoperfusion during early reperfusion (6 hours); however, blood flow defects at later recovery time points remain to be excluded. These results may have implications for HS therapy in clinical ischemic stroke.
authors.affiliation: Departments of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bhardwaj
authors.forename: I
authors.initials: I
authors.lastname: Harukuni
authors.forename: S J
authors.initials: SJ
authors.lastname: Murphy
authors.forename: N J
authors.initials: NJ
authors.lastname: Alkayed
authors.forename: B J
authors.initials: BJ
authors.lastname: Crain
authors.forename: R C
authors.initials: RC
authors.lastname: Koehler
authors.forename: P D
authors.initials: PD
authors.lastname: Hurn
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
mesh_terms: D000818:Animals; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004234:Diuretics, Osmotic / Q000494:pharmacology; D006982:Hypertonic Solutions / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D004234:Diuretics, Osmotic; D006982:Hypertonic Solutions; D008353:Mannitol; D012965:Sodium Chloride