An early bolus of hypertonic saline hydroxyethyl starch improves long-term outcome after global cerebral ischemia

Ruediger R. Noppens, Michael Christ, Ansgar Brambrink, Ines Koerner, Axel Heimann, Oliver Kempski

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

OBJECTIVE: The beneficial effect of hypertonic saline solutions in the emergency treatment of shock and traumatic brain injury is well described. The present study determines effects of a single bolus of hypertonic saline on long-term survival, neurologic function, and neuronal survival 10 days after global cerebral ischemia. In addition, we evaluated the therapeutic window for hypertonic saline treatment (early vs. delayed application). DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Male Wistar rats weighing 240-330 g. INTERVENTIONS: Rats were submitted to temporal global cerebral ischemia using temporary bilateral carotid occlusion combined with hypobaric hypotension. Animals received 7.5% saline/6% hydroxyethyl starch (HHS) or vehicle (NaCl 0.9%) at either 1.5 mins (early treatment) or 31.5 mins (delayed treatment) of reperfusion. Regional cerebral blood flow (rCBF) and physiologic variables were measured during insult and early reperfusion. Animal survival and neurologic function were evaluated throughout the 10-day observation period. Quantification of brain injury was performed on day 10. MEASUREMENTS AND MAIN RESULTS: Early treatment with HHS resulted in a robust restoration of rCBF after ischemia, reduced postischemic mortality by 77% (9% vs. 39% in vehicle-treated controls), ameliorated neurologic performance (Neuro-Deficit-Score 10 days after insult, 96 ± 0.7 vs. 85 ± 1.4, mean ± se), and almost blunted neuronal cell death (hippocampal CA1, 2150 ± 191 vs. 884 ± 141 neurons/mm; cortex, 1746 ± 91 vs. 1060 ± 112). In contrast, delayed treatment resulted in no sustained effects. CONCLUSIONS: Timing of HHS treatment is critical after experimental global cerebral ischemia to reduce mortality, improve neurologic function, and neuronal survival. Our results suggest that early application of HHS may be a potential neuroprotective strategy after global cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)2194-2200
Number of pages7
JournalCritical Care Medicine
Volume34
Issue number8
DOIs
StatePublished - Aug 2006
Externally publishedYes

Fingerprint

Brain Ischemia
Starch
Nervous System
Cerebrovascular Circulation
Regional Blood Flow
Reperfusion
Therapeutics
Hypertonic Saline Solutions
Emergency Treatment
Mortality
Hypotension
Brain Injuries
Wistar Rats
Shock
Cell Death
Ischemia
Observation
Neurons

Keywords

  • Cerebral ischemia
  • Cerebral resuscitation
  • Histopathology
  • Hydroxyethyl starch
  • Hypertonic saline
  • Neurological deficit
  • Rats
  • Survival

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

An early bolus of hypertonic saline hydroxyethyl starch improves long-term outcome after global cerebral ischemia. / Noppens, Ruediger R.; Christ, Michael; Brambrink, Ansgar; Koerner, Ines; Heimann, Axel; Kempski, Oliver.

In: Critical Care Medicine, Vol. 34, No. 8, 08.2006, p. 2194-2200.

Research output: Contribution to journalArticle

Noppens, Ruediger R. ; Christ, Michael ; Brambrink, Ansgar ; Koerner, Ines ; Heimann, Axel ; Kempski, Oliver. / An early bolus of hypertonic saline hydroxyethyl starch improves long-term outcome after global cerebral ischemia. In: Critical Care Medicine. 2006 ; Vol. 34, No. 8. pp. 2194-2200.
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abstract = "OBJECTIVE: The beneficial effect of hypertonic saline solutions in the emergency treatment of shock and traumatic brain injury is well described. The present study determines effects of a single bolus of hypertonic saline on long-term survival, neurologic function, and neuronal survival 10 days after global cerebral ischemia. In addition, we evaluated the therapeutic window for hypertonic saline treatment (early vs. delayed application). DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Male Wistar rats weighing 240-330 g. INTERVENTIONS: Rats were submitted to temporal global cerebral ischemia using temporary bilateral carotid occlusion combined with hypobaric hypotension. Animals received 7.5{\%} saline/6{\%} hydroxyethyl starch (HHS) or vehicle (NaCl 0.9{\%}) at either 1.5 mins (early treatment) or 31.5 mins (delayed treatment) of reperfusion. Regional cerebral blood flow (rCBF) and physiologic variables were measured during insult and early reperfusion. Animal survival and neurologic function were evaluated throughout the 10-day observation period. Quantification of brain injury was performed on day 10. MEASUREMENTS AND MAIN RESULTS: Early treatment with HHS resulted in a robust restoration of rCBF after ischemia, reduced postischemic mortality by 77{\%} (9{\%} vs. 39{\%} in vehicle-treated controls), ameliorated neurologic performance (Neuro-Deficit-Score 10 days after insult, 96 ± 0.7 vs. 85 ± 1.4, mean ± se), and almost blunted neuronal cell death (hippocampal CA1, 2150 ± 191 vs. 884 ± 141 neurons/mm; cortex, 1746 ± 91 vs. 1060 ± 112). In contrast, delayed treatment resulted in no sustained effects. CONCLUSIONS: Timing of HHS treatment is critical after experimental global cerebral ischemia to reduce mortality, improve neurologic function, and neuronal survival. Our results suggest that early application of HHS may be a potential neuroprotective strategy after global cerebral ischemia.",
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AU - Christ, Michael

AU - Brambrink, Ansgar

AU - Koerner, Ines

AU - Heimann, Axel

AU - Kempski, Oliver

PY - 2006/8

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N2 - OBJECTIVE: The beneficial effect of hypertonic saline solutions in the emergency treatment of shock and traumatic brain injury is well described. The present study determines effects of a single bolus of hypertonic saline on long-term survival, neurologic function, and neuronal survival 10 days after global cerebral ischemia. In addition, we evaluated the therapeutic window for hypertonic saline treatment (early vs. delayed application). DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Male Wistar rats weighing 240-330 g. INTERVENTIONS: Rats were submitted to temporal global cerebral ischemia using temporary bilateral carotid occlusion combined with hypobaric hypotension. Animals received 7.5% saline/6% hydroxyethyl starch (HHS) or vehicle (NaCl 0.9%) at either 1.5 mins (early treatment) or 31.5 mins (delayed treatment) of reperfusion. Regional cerebral blood flow (rCBF) and physiologic variables were measured during insult and early reperfusion. Animal survival and neurologic function were evaluated throughout the 10-day observation period. Quantification of brain injury was performed on day 10. MEASUREMENTS AND MAIN RESULTS: Early treatment with HHS resulted in a robust restoration of rCBF after ischemia, reduced postischemic mortality by 77% (9% vs. 39% in vehicle-treated controls), ameliorated neurologic performance (Neuro-Deficit-Score 10 days after insult, 96 ± 0.7 vs. 85 ± 1.4, mean ± se), and almost blunted neuronal cell death (hippocampal CA1, 2150 ± 191 vs. 884 ± 141 neurons/mm; cortex, 1746 ± 91 vs. 1060 ± 112). In contrast, delayed treatment resulted in no sustained effects. CONCLUSIONS: Timing of HHS treatment is critical after experimental global cerebral ischemia to reduce mortality, improve neurologic function, and neuronal survival. Our results suggest that early application of HHS may be a potential neuroprotective strategy after global cerebral ischemia.

AB - OBJECTIVE: The beneficial effect of hypertonic saline solutions in the emergency treatment of shock and traumatic brain injury is well described. The present study determines effects of a single bolus of hypertonic saline on long-term survival, neurologic function, and neuronal survival 10 days after global cerebral ischemia. In addition, we evaluated the therapeutic window for hypertonic saline treatment (early vs. delayed application). DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Male Wistar rats weighing 240-330 g. INTERVENTIONS: Rats were submitted to temporal global cerebral ischemia using temporary bilateral carotid occlusion combined with hypobaric hypotension. Animals received 7.5% saline/6% hydroxyethyl starch (HHS) or vehicle (NaCl 0.9%) at either 1.5 mins (early treatment) or 31.5 mins (delayed treatment) of reperfusion. Regional cerebral blood flow (rCBF) and physiologic variables were measured during insult and early reperfusion. Animal survival and neurologic function were evaluated throughout the 10-day observation period. Quantification of brain injury was performed on day 10. MEASUREMENTS AND MAIN RESULTS: Early treatment with HHS resulted in a robust restoration of rCBF after ischemia, reduced postischemic mortality by 77% (9% vs. 39% in vehicle-treated controls), ameliorated neurologic performance (Neuro-Deficit-Score 10 days after insult, 96 ± 0.7 vs. 85 ± 1.4, mean ± se), and almost blunted neuronal cell death (hippocampal CA1, 2150 ± 191 vs. 884 ± 141 neurons/mm; cortex, 1746 ± 91 vs. 1060 ± 112). In contrast, delayed treatment resulted in no sustained effects. CONCLUSIONS: Timing of HHS treatment is critical after experimental global cerebral ischemia to reduce mortality, improve neurologic function, and neuronal survival. Our results suggest that early application of HHS may be a potential neuroprotective strategy after global cerebral ischemia.

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KW - Cerebral resuscitation

KW - Histopathology

KW - Hydroxyethyl starch

KW - Hypertonic saline

KW - Neurological deficit

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