title: Increases in lung and brain water following experimental stroke: effect of mannitol and hypertonic saline.
abstract: OBJECTIVE
  Pulmonary edema is a serious condition following brain injury of diverse etiologies, including large hemispheric infarctions. We have previously shown that treatment with hypertonic saline attenuates cerebral edema associated with experimental ischemic stroke. In a well-characterized animal model of large ischemic stroke, we tested the hypotheses that lung water increases following cerebral ischemia and determined the effects of osmotherapy with hypertonic saline and mannitol on total lung water, as well as on cerebral edema.
  
  
  METHODS
  Prospective laboratory animal study.
  
  
  METHODS
  Research laboratory in a university teaching hospital.
  
  
  METHODS
  Adult male Wistar rats (300-450 g, n = 103).
  
  
  METHODS
  Under controlled conditions of normoxia, normocarbia, and normothermia, spontaneously breathing, halothane-anesthetized (1.0-1.5%) rats were subjected to permanent middle cerebral artery occlusion by the intraluminal occlusion technique.
  
  
  RESULTS
  Cerebral perfusion was monitored by laser-Doppler flowmetry over ipsilateral parietal cortex to ensure adequate vascular occlusion. At 6 hrs following middle cerebral artery occlusion, rats were treated in a blinded randomized fashion with no intravenous fluids (n = 24), a continuous intravenous infusion (0.3 mL/hr) of 0.9% saline (n = 21), 20% mannitol (2 g/Kg) (n = 20), 5% hypertonic saline (n = 20), or 7.5% hypertonic saline (n = 18) as a chloride/acetate mixture (50:50) until the end of the experiment. Brains and lungs were harvested, and tissue water content was estimated by comparing wet-to-dry weight ratios of ipsilateral and contralateral cerebral hemispheres at 48 hrs postischemia. Sham-operated rats served as controls (n = 20). Serum osmolality was determined at the end of the experiment in all animals. Lung water content was increased significantly in rats subjected to middle cerebral artery occlusion and treated with no intravenous fluids (76.7 +/- 0.7%, 317 +/- 7 mOsm/L) (mean +/- sd) and saline (76.8 +/- 1.2%, 311 +/- 10 mOsm/L), compared with sham-operated controls (74.5 +/- 0.9%, 302 +/- 4 mOsm/L). Treatment with 20% mannitol (74.4 +/- 1.2%, 352 +/- 15 mOsm/L), 5% hypertonic saline (75.6 +/- 1.3%, 339 +/- 16 mOsm/L), and 7.5% hypertonic saline (74.9 +/- 0.7%, 360 +/- 23 mOsm/L) significantly attenuated lung water content. Hemispheric brain water content increased both in the ipsilateral ischemic and contralateral hemispheres treated with saline (ipsilateral, 85.1 +/- 1.7%; contralateral, 80.7 +/- 0.7%), compared with sham-operated controls (ipsilateral, 79.6 +/- 0.9%; contralateral, 79.5 +/- 0.9%), as well as in rats that received no fluids (ipsilateral, 84.6 +/- 1.8%; contralateral, 80.4 +/- 0.9%). Treatment with 5% hypertonic saline (ipsilateral, 83.8 +/- 1.0%; contralateral, 79.7 +/- 0.6%) and 7.5% hypertonic saline (ipsilateral, 82.3 +/- 1.3%; contralateral, 78.6 +/- 0.7%) resulted in attenuation of stroke-associated increases in brain water content to a greater extent than mannitol (ipsilateral, 83.6 +/- 1.6%; contralateral, 79.1 +/- 1.0%).
  
  
  CONCLUSIONS
  In a well-characterized animal model of large ischemic stroke, total lung water content increases, which is likely neurogenic in origin. Attenuation of stroke-associated increases in lung and brain water content with continuous infusion of hypertonic saline may have therapeutic implication in the treatment of cerebral and pulmonary edema following ischemic stroke.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Thomas J K
authors.initials: TJ
authors.lastname: Toung
authors.forename: Yi
authors.initials: Y
authors.lastname: Chang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lin
authors.forename: Anish
authors.initials: A
authors.lastname: Bhardwaj
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000503:physiopathology*; D004292:Dominance, Cerebral / Q000502:physiology; D015633:Extravascular Lung Water / Q000187:drug effects* / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D012462:Saline Solution, Hypertonic; D008353:Mannitol