Controlled release of lipopolysaccharide in the subarachnoid space of rabbits induces chronic vasospasm in the absence of blood

Pablo F. Recinos, Gustavo Pradilla, Quoc-Anh Thai, Marilyn Perez, Alia M. Hdeib, Rafael J Tamargo

Research output: Contribution to journalArticle

Abstract

Objective: Leukocyte-endothelial cell interactions appear to play a role in the development of vasospasm after SAH. Using a purely inflammatory protein, LPS, we evaluated the effect of inflammation on the development of chronic vasospasm in the absence of blood and compared it to SAH-induced vasospasm in rabbits. Methods: Lipopolysaccharide was incorporated into EVAc polymers to produce 20% LPS/EVAc polymers (wt/wt). Rabbits (n = 23) were randomized to 4 experimental groups: (1) empty polymer (n = 6), (2) SAH (n = 5), (3) 0.7 mg/kg polymeric LPS dose (n = 6), and (4) 1.4 mg/kg polymeric LPS dose (n = 6). Blood and polymers were inserted into the cisterna magna. The rabbits were killed 3 days postoperatively, and the basilar arteries were harvested for morphometric analysis. Clinical response and lumen patencies were analyzed using ANOVA and a post hoc Newman-Keuls Multiple Comparisons test. Results: Significant narrowing of the basilar artery was observed by insertion of 20% LPS/EVAc polymers into the subarachnoid space at a polymeric dose of 1.4 mg/kg (actual dose, 66 μg kg-1 d-1) (75.4% ± 4.2%; P <.01) and by SAH (80.3% ± 8.1%; P <.01) as compared with the empty polymer group. A trend toward narrowing was observed in the 0.7 mg/kg polymeric LPS dose group (actual dose, 33 μg kg-1 d-1) (85.2% ± 2.6%; P > .05). Symptoms associated with SAH were noted in 50% of the rabbits in the 0.7 mg/kg LPS group and in 100% of rabbits in the 1.4 mg/kg LPS group. Conclusion: Controlled release of LPS into the subarachnoid space of rabbits produced chronic vasospasm in a dose-dependent manner. At a polymeric dose of 1.4 mg/kg, LPS-induced vasospasm was equivalent to that induced by SAH. This suggests that LPS and SAH may induce vasospasm through similar mechanisms and provides further evidence that inflammation plays a central role in the etiology of chronic vasospasm.

Original languageEnglish (US)
Pages (from-to)463-469
Number of pages7
JournalSurgical Neurology
Volume66
Issue number5
DOIs
StatePublished - Nov 2006

Fingerprint

Subarachnoid Space
Lipopolysaccharides
Polymers
Rabbits
Basilar Artery
Cisterna Magna
Inflammation
Cell Communication
Analysis of Variance
Leukocytes
Endothelial Cells
Proteins

Keywords

  • Endotoxin
  • Lipopolysaccharide
  • Rabbit
  • Rabbits
  • Subarachnoid hemorrhage
  • Vasospasm

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Controlled release of lipopolysaccharide in the subarachnoid space of rabbits induces chronic vasospasm in the absence of blood. / Recinos, Pablo F.; Pradilla, Gustavo; Thai, Quoc-Anh; Perez, Marilyn; Hdeib, Alia M.; Tamargo, Rafael J.

In: Surgical Neurology, Vol. 66, No. 5, 11.2006, p. 463-469.

Research output: Contribution to journalArticle

Recinos, Pablo F. ; Pradilla, Gustavo ; Thai, Quoc-Anh ; Perez, Marilyn ; Hdeib, Alia M. ; Tamargo, Rafael J. / Controlled release of lipopolysaccharide in the subarachnoid space of rabbits induces chronic vasospasm in the absence of blood. In: Surgical Neurology. 2006 ; Vol. 66, No. 5. pp. 463-469.
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abstract = "Objective: Leukocyte-endothelial cell interactions appear to play a role in the development of vasospasm after SAH. Using a purely inflammatory protein, LPS, we evaluated the effect of inflammation on the development of chronic vasospasm in the absence of blood and compared it to SAH-induced vasospasm in rabbits. Methods: Lipopolysaccharide was incorporated into EVAc polymers to produce 20{\%} LPS/EVAc polymers (wt/wt). Rabbits (n = 23) were randomized to 4 experimental groups: (1) empty polymer (n = 6), (2) SAH (n = 5), (3) 0.7 mg/kg polymeric LPS dose (n = 6), and (4) 1.4 mg/kg polymeric LPS dose (n = 6). Blood and polymers were inserted into the cisterna magna. The rabbits were killed 3 days postoperatively, and the basilar arteries were harvested for morphometric analysis. Clinical response and lumen patencies were analyzed using ANOVA and a post hoc Newman-Keuls Multiple Comparisons test. Results: Significant narrowing of the basilar artery was observed by insertion of 20{\%} LPS/EVAc polymers into the subarachnoid space at a polymeric dose of 1.4 mg/kg (actual dose, 66 μg kg-1 d-1) (75.4{\%} ± 4.2{\%}; P <.01) and by SAH (80.3{\%} ± 8.1{\%}; P <.01) as compared with the empty polymer group. A trend toward narrowing was observed in the 0.7 mg/kg polymeric LPS dose group (actual dose, 33 μg kg-1 d-1) (85.2{\%} ± 2.6{\%}; P > .05). Symptoms associated with SAH were noted in 50{\%} of the rabbits in the 0.7 mg/kg LPS group and in 100{\%} of rabbits in the 1.4 mg/kg LPS group. Conclusion: Controlled release of LPS into the subarachnoid space of rabbits produced chronic vasospasm in a dose-dependent manner. At a polymeric dose of 1.4 mg/kg, LPS-induced vasospasm was equivalent to that induced by SAH. This suggests that LPS and SAH may induce vasospasm through similar mechanisms and provides further evidence that inflammation plays a central role in the etiology of chronic vasospasm.",
keywords = "Endotoxin, Lipopolysaccharide, Rabbit, Rabbits, Subarachnoid hemorrhage, Vasospasm",
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T1 - Controlled release of lipopolysaccharide in the subarachnoid space of rabbits induces chronic vasospasm in the absence of blood

AU - Recinos, Pablo F.

AU - Pradilla, Gustavo

AU - Thai, Quoc-Anh

AU - Perez, Marilyn

AU - Hdeib, Alia M.

AU - Tamargo, Rafael J

PY - 2006/11

Y1 - 2006/11

N2 - Objective: Leukocyte-endothelial cell interactions appear to play a role in the development of vasospasm after SAH. Using a purely inflammatory protein, LPS, we evaluated the effect of inflammation on the development of chronic vasospasm in the absence of blood and compared it to SAH-induced vasospasm in rabbits. Methods: Lipopolysaccharide was incorporated into EVAc polymers to produce 20% LPS/EVAc polymers (wt/wt). Rabbits (n = 23) were randomized to 4 experimental groups: (1) empty polymer (n = 6), (2) SAH (n = 5), (3) 0.7 mg/kg polymeric LPS dose (n = 6), and (4) 1.4 mg/kg polymeric LPS dose (n = 6). Blood and polymers were inserted into the cisterna magna. The rabbits were killed 3 days postoperatively, and the basilar arteries were harvested for morphometric analysis. Clinical response and lumen patencies were analyzed using ANOVA and a post hoc Newman-Keuls Multiple Comparisons test. Results: Significant narrowing of the basilar artery was observed by insertion of 20% LPS/EVAc polymers into the subarachnoid space at a polymeric dose of 1.4 mg/kg (actual dose, 66 μg kg-1 d-1) (75.4% ± 4.2%; P <.01) and by SAH (80.3% ± 8.1%; P <.01) as compared with the empty polymer group. A trend toward narrowing was observed in the 0.7 mg/kg polymeric LPS dose group (actual dose, 33 μg kg-1 d-1) (85.2% ± 2.6%; P > .05). Symptoms associated with SAH were noted in 50% of the rabbits in the 0.7 mg/kg LPS group and in 100% of rabbits in the 1.4 mg/kg LPS group. Conclusion: Controlled release of LPS into the subarachnoid space of rabbits produced chronic vasospasm in a dose-dependent manner. At a polymeric dose of 1.4 mg/kg, LPS-induced vasospasm was equivalent to that induced by SAH. This suggests that LPS and SAH may induce vasospasm through similar mechanisms and provides further evidence that inflammation plays a central role in the etiology of chronic vasospasm.

AB - Objective: Leukocyte-endothelial cell interactions appear to play a role in the development of vasospasm after SAH. Using a purely inflammatory protein, LPS, we evaluated the effect of inflammation on the development of chronic vasospasm in the absence of blood and compared it to SAH-induced vasospasm in rabbits. Methods: Lipopolysaccharide was incorporated into EVAc polymers to produce 20% LPS/EVAc polymers (wt/wt). Rabbits (n = 23) were randomized to 4 experimental groups: (1) empty polymer (n = 6), (2) SAH (n = 5), (3) 0.7 mg/kg polymeric LPS dose (n = 6), and (4) 1.4 mg/kg polymeric LPS dose (n = 6). Blood and polymers were inserted into the cisterna magna. The rabbits were killed 3 days postoperatively, and the basilar arteries were harvested for morphometric analysis. Clinical response and lumen patencies were analyzed using ANOVA and a post hoc Newman-Keuls Multiple Comparisons test. Results: Significant narrowing of the basilar artery was observed by insertion of 20% LPS/EVAc polymers into the subarachnoid space at a polymeric dose of 1.4 mg/kg (actual dose, 66 μg kg-1 d-1) (75.4% ± 4.2%; P <.01) and by SAH (80.3% ± 8.1%; P <.01) as compared with the empty polymer group. A trend toward narrowing was observed in the 0.7 mg/kg polymeric LPS dose group (actual dose, 33 μg kg-1 d-1) (85.2% ± 2.6%; P > .05). Symptoms associated with SAH were noted in 50% of the rabbits in the 0.7 mg/kg LPS group and in 100% of rabbits in the 1.4 mg/kg LPS group. Conclusion: Controlled release of LPS into the subarachnoid space of rabbits produced chronic vasospasm in a dose-dependent manner. At a polymeric dose of 1.4 mg/kg, LPS-induced vasospasm was equivalent to that induced by SAH. This suggests that LPS and SAH may induce vasospasm through similar mechanisms and provides further evidence that inflammation plays a central role in the etiology of chronic vasospasm.

KW - Endotoxin

KW - Lipopolysaccharide

KW - Rabbit

KW - Rabbits

KW - Subarachnoid hemorrhage

KW - Vasospasm

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