Hypertonic saline worsens infarct volume after transient focal ischemia in rats

Anish Bhardwaj, Izumi Harukuni, Stephanie J. Murphy, Nabil J. Alkayed, Barbara J. Crain, Raymond C. Koehler, Patricia D. Hurn, Richard J. Traystman

Research output: Contribution to journalArticle

57 Citations (Scopus)

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; P<0.05) than in SAL (64±15 mm3; 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 languageEnglish (US)
Pages (from-to)1694-1701
Number of pages8
JournalStroke
Volume31
Issue number7
StatePublished - Jul 2000
Externally publishedYes

Fingerprint

Reperfusion
Ischemia
Cerebrovascular Circulation
Middle Cerebral Artery Infarction
Transient Ischemic Attack
Regional Blood Flow
Mannitol
Hypernatremia
Corpus Striatum
Brain Edema
Halothane
Serum
Radiography
Wistar Rats
Chlorides
Acetates
Lasers
Stroke
Therapeutics

Keywords

  • Infarction
  • Ischemia, focal
  • Mannitol
  • Osmolar concentration
  • Reperfusion
  • Saline solution, hypertonic

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Bhardwaj, A., Harukuni, I., Murphy, S. J., Alkayed, N. J., Crain, B. J., Koehler, R. C., ... Traystman, R. J. (2000). Hypertonic saline worsens infarct volume after transient focal ischemia in rats. Stroke, 31(7), 1694-1701.

Hypertonic saline worsens infarct volume after transient focal ischemia in rats. / Bhardwaj, Anish; Harukuni, Izumi; Murphy, Stephanie J.; Alkayed, Nabil J.; 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 journalArticle

Bhardwaj, A, Harukuni, I, Murphy, SJ, Alkayed, NJ, Crain, BJ, Koehler, RC, Hurn, PD & Traystman, RJ 2000, 'Hypertonic saline worsens infarct volume after transient focal ischemia in rats', Stroke, vol. 31, no. 7, pp. 1694-1701.
Bhardwaj A, Harukuni I, Murphy SJ, Alkayed NJ, Crain BJ, Koehler RC et al. Hypertonic saline worsens infarct volume after transient focal ischemia in rats. Stroke. 2000 Jul;31(7):1694-1701.
Bhardwaj, Anish ; Harukuni, Izumi ; Murphy, Stephanie J. ; Alkayed, Nabil J. ; Crain, Barbara J. ; Koehler, Raymond C. ; Hurn, Patricia D. ; Traystman, Richard J. / Hypertonic saline worsens infarct volume after transient focal ischemia in rats. In: Stroke. 2000 ; Vol. 31, No. 7. pp. 1694-1701.
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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; P<0.05) than in SAL (64±15 mm3; 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.",
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author = "Anish Bhardwaj and Izumi Harukuni and Murphy, {Stephanie J.} and Alkayed, {Nabil J.} and Crain, {Barbara J.} and Koehler, {Raymond C.} and Hurn, {Patricia D.} and Traystman, {Richard J.}",
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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 J.

AU - Crain, Barbara J.

AU - Koehler, Raymond C.

AU - Hurn, Patricia D.

AU - Traystman, Richard J.

PY - 2000/7

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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; P<0.05) than in SAL (64±15 mm3; 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; P<0.05) than in SAL (64±15 mm3; 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

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