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, 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 ([14C]iodoantipyrine auto radiography) 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 mm3; 30±3% of contralateral cortex; P3; 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 c 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1694-1701 |
| Number of pages | 8 |
| Journal | Stroke |
| Volume | 31 |
| Issue number | 7 |
| State | Published - Jul 2000 |
| Externally published | Yes |
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Keywords
- Infarction
- Ischemia, focal
- Mannitol
- Osmolar concentration
- Reperfusion
- Saline solution, hypertonic
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Neuroscience(all)
Cite this
Hypertonic saline worsens infarct volume after transient focal ischemia in rats. / Bhardwaj, Anish; Harukuni, Izumi; Murphy, Stephanie J.; Alkayed, Nabil; Crain, Barbara J.; Koehler, Raymond C.; Hurn, Patricia D.; Traystman, Richard J.
In: Stroke, Vol. 31, No. 7, 07.2000, p. 1694-1701.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hypertonic saline worsens infarct volume after transient focal ischemia in rats
AU - Bhardwaj, Anish
AU - Harukuni, Izumi
AU - Murphy, Stephanie J.
AU - Alkayed, Nabil
AU - Crain, Barbara J.
AU - Koehler, Raymond C.
AU - Hurn, Patricia D.
AU - Traystman, Richard J.
PY - 2000/7
Y1 - 2000/7
N2 - 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, 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 ([14C]iodoantipyrine auto radiography) 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 mm3; 30±3% of contralateral cortex; P3; 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 c 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.
AB - 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, 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 ([14C]iodoantipyrine auto radiography) 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 mm3; 30±3% of contralateral cortex; P3; 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 c 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.
KW - Infarction
KW - Ischemia, focal
KW - Mannitol
KW - Osmolar concentration
KW - Reperfusion
KW - Saline solution, hypertonic
UR - http://www.scopus.com/inward/record.url?scp=0033934996&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033934996&partnerID=8YFLogxK
M3 - Article
C2 - 10884475
AN - SCOPUS:0033934996
VL - 31
SP - 1694
EP - 1701
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 7
ER -