Lipopolysaccharide preconditioning induces robust protection against brain injury resulting from deep hypothermic circulatory arrest

Edward J. Hickey, Xiaomang You, Vassil Kaimaktchiev, Mary Stenzel-Poore, Ross M. Ungerleider

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Objective: Delayed preconditioning genetically reprograms the response to ischemic injury. Subclinical bacterial lipopolysaccharide acts through preconditioning, powerfully protecting against experimental stroke. We investigated the potential for lipopolysaccharide to protect against brain injury related to cardiopulmonary bypass. Methods: Neonatal piglets were blindly and randomly preconditioned with lipopolysaccharide (n = 6) or saline (n = 6). Three days later, they experienced 2 hours of deep hypothermic circulatory arrest before being weaned and supported anesthetized for 20 hours in an intensive care setting. Controls included cardiopulmonary bypass without deep hypothermic circulatory arrest (n = 3) and no cardiopulmonary bypass (n = 3). Brain injury was quantified by light and fluorescent microscopy (Fluoro-Jade; Histo-Chem, Inc, Jefferson, Ark). Results: All animals were clinically indistinguishable before surgery. Perioperative and postoperative parameters between experimental groups were similar. No control animal scored falsely positive. Histologic scores were 0.33 ± 0.21, 0.66 ± 0.42, and 0.5 ± 0.24 in the cortex, basal ganglia, and hippocampus, respectively, in the lipopolysaccharide-treated animals but significantly worse in all saline control animals (1.33 ± 0.21, P <.01; 1.66 ± 0.33, P = .09; and 6.0 ± 1.5, P <.01). One lipopolysaccharide-treated brain was histologically indistinguishable from controls. Conclusion: This is the first evidence that lipopolysaccharide can precondition against cardiopulmonary bypass-related injury. Because lipopolysaccharide preconditioning is a systemic phenomenon offering proven protection against myocardial, hepatic, and pulmonary injury, this technique offers enormous potential for protecting against systemic neonatal injury related to cardiopulmonary bypass.

Original languageEnglish (US)
Pages (from-to)1588-1596
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume133
Issue number6
DOIs
StatePublished - Jun 2007

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Deep Hypothermia Induced Circulatory Arrest
Brain Injuries
Lipopolysaccharides
Cardiopulmonary Bypass
Wounds and Injuries
Lung Injury
Critical Care
Basal Ganglia
Microscopy
Hippocampus
Stroke
Light
Liver
Brain

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Lipopolysaccharide preconditioning induces robust protection against brain injury resulting from deep hypothermic circulatory arrest. / Hickey, Edward J.; You, Xiaomang; Kaimaktchiev, Vassil; Stenzel-Poore, Mary; Ungerleider, Ross M.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 133, No. 6, 06.2007, p. 1588-1596.

Research output: Contribution to journalArticle

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abstract = "Objective: Delayed preconditioning genetically reprograms the response to ischemic injury. Subclinical bacterial lipopolysaccharide acts through preconditioning, powerfully protecting against experimental stroke. We investigated the potential for lipopolysaccharide to protect against brain injury related to cardiopulmonary bypass. Methods: Neonatal piglets were blindly and randomly preconditioned with lipopolysaccharide (n = 6) or saline (n = 6). Three days later, they experienced 2 hours of deep hypothermic circulatory arrest before being weaned and supported anesthetized for 20 hours in an intensive care setting. Controls included cardiopulmonary bypass without deep hypothermic circulatory arrest (n = 3) and no cardiopulmonary bypass (n = 3). Brain injury was quantified by light and fluorescent microscopy (Fluoro-Jade; Histo-Chem, Inc, Jefferson, Ark). Results: All animals were clinically indistinguishable before surgery. Perioperative and postoperative parameters between experimental groups were similar. No control animal scored falsely positive. Histologic scores were 0.33 ± 0.21, 0.66 ± 0.42, and 0.5 ± 0.24 in the cortex, basal ganglia, and hippocampus, respectively, in the lipopolysaccharide-treated animals but significantly worse in all saline control animals (1.33 ± 0.21, P <.01; 1.66 ± 0.33, P = .09; and 6.0 ± 1.5, P <.01). One lipopolysaccharide-treated brain was histologically indistinguishable from controls. Conclusion: This is the first evidence that lipopolysaccharide can precondition against cardiopulmonary bypass-related injury. Because lipopolysaccharide preconditioning is a systemic phenomenon offering proven protection against myocardial, hepatic, and pulmonary injury, this technique offers enormous potential for protecting against systemic neonatal injury related to cardiopulmonary bypass.",
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