Hypertonic saline worsens infarct volume after transient focal ischemia inrats

Background and Purpose-Hypertonic saline (HS) has been advocated as a hyper osmolar agent for the treatment of cerebral edema, especially after traumat ic brain injury. We tested the hypothesis that continuous intravenous HS ad ministered during reperfusion from transient focal cerebral ischemia attenu ates infarct volume. Methods-Halothane-anesthetized male Wistar rats were subjected to 2 hours o f middle cerebral artery occlusion (MCAO) by the intraluminal occlusion tec hnique. At the onset of reperfusion, rats received a 10-mL/kg intravenous b olus 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 exp eriments, ischemic damage was determined in cohorts treated with equivolume tric 3% saline (n = 8) or 20% mannitol (n = 8). In a third series, regional cerebral blood now was measured ([C-14]iodoantipyrine autoradiography) at 6 hours of reperfusion in 7.5%-SAL-treated (n = 5) or SAL-treated (n = 5) a nimals. Results-In SAL rats, serum Na+ was 137+/-3 and 138+/-2 mEq/L (mean+/-SEM) a t baseline and 22 hours of reperfusion, respectively. In 7.5% SAL, serum Na f was 136+/-2 and 154+/-2 mEq/L at baseline and reperfusion, respectively. Physiological variables and reduction in laser-Doppler signal during MCAO a nd early reperfusion were not different between the 2 treatment groups. Cor tical 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 thera py. Ipsilateral cortical tissue volume was increased relative to the contra lateral aide (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 heterogeneou s in all animals, but there was no evidence of postischemic hypoperfusion o r blood flow maldistribution in 7.5%-SAL-treated animals. Conclusions-These data demonstrate that hypernatremia resulting from postis chemic HS infusion worsens cortical infarct volume in transient focal cereb ral ischemia. The deleterious effect is not linked to exacerbation of delay ed hypoperfusion during early reperfusion (6 hours); however, blood flow de fects at later recovery time points remain to be excluded. These results ma y have implications for HS therapy in clinical ischemic stroke.