Hypertonic Saline Worsens Infarct Volume After Transient Focal Ischemia in Rats

Abstract

Background and Purpose-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, nϭ8) or 7.5% SAL (chloride:acetate 50:50, nϭ8) 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 (nϭ8) or 20% mannitol (nϭ8). In a third series, regional cerebral blood flow was measured ([ 14 C]iodoantipyrine autoradiography) at 6 hours of reperfusion in 7.5%-SAL-treated (nϭ5) or SAL-treated (nϭ5) animals. Results-In SAL rats, serum Na ϩ was 137Ϯ3 and 138Ϯ2 mEq/L (meanϮSEM) at baseline and 22 hours of reperfusion, respectively. In 7.5% SAL, serum Na ϩ was 136Ϯ2 and 154Ϯ2 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 (121Ϯ14 mm 3 ; 30Ϯ3% of contralateral cortex; PϽ0.05) than in SAL (64Ϯ15 mm 3 ; 16Ϯ4% of contralateral cortex). Striatal infarct volume was unchanged by HS therapy. Ipsilateral cortical tissue volume was increased relative to the contralateral side (by 26Ϯ5% with SAL; by 41Ϯ5% 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. (Stroke.

Effect of Duration of Osmotherapy on Blood–Brain Barrier Disruption and Regional Cerebral Edema after Experimental Stroke

“…In our previous study, the temporal profile of ischemiaevoked increases in brain water content (Toung et al, 2002) suggested a major vasogenic etiology, rather than cytotoxic edema secondary to postischemic energy failure. We have previously shown that institution of a hyperosmolar state with continuous infusion of HS when started at the onset of reperfusion in our rat model of transient focal ischemia worsened infarct volume (Bhardwaj et al, 2000). The explanation for the observed worsening of infarct volume is not readily evident at present, but the mechanism of this detrimental effect was not due to maldistribution of regional CBF.…”

Effects of Mannitol on Ischemia-Induced Degeneration in Rat Hippocampus

“…Some experimental data on focal ischemia demonstrate the adverse effects of mannitol on the brain (19). Most of reports on the effects of mannitol have been based on in vivo experiments, in which the effects of mannitol are evaluated by histological examinations based on fixed and stained brain preparations.…”

“…On the other hand mannitol has been reported to worsen the infarct volume after transient focal ischemia in rat cortex, caudoputamen complex, and hemisphere in rats (19). It was also reported that mannitol did not have any effect on energy metabolism in forebrain ischemia (20).…”

Management of intracranial hypertension: Recent advances and future directions

“…Like mannitol, it may also cause rebound ICH, but the evidences are also less convincing. [65][66] Many studies have compared mannitol with HTS with most in favour of HTS. HTS seems to have a greater and longer lasting reduction of ICP than mannitol, 67 is even effective in decreasing ICP refractory to mannitol 68 and also has less failure rates.…”