Increases in lung and brain water following experimental stroke: Effect of mannitol and hypertonic saline

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. DESIGN:Prospective laboratory animal study. SETTING:Research laboratory in a university teaching hospital. SUBJECTS:Adult male Wistar rats (300–450 g, n = 103). INTERVENTIONS: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. MEASUREMENTS AND MAIN 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%),