TY - JOUR
T1 - Lipopolysaccharide preconditioning induces robust protection against brain injury resulting from deep hypothermic circulatory arrest
AU - Hickey, Edward J.
AU - You, Xiaomang
AU - Kaimaktchiev, Vassil
AU - Stenzel-Poore, Mary
AU - Ungerleider, Ross M.
N1 - Funding Information:
Supported by generous grants from the Medical Research Foundation of Oregon and the Children’s Heart Foundation, which have funded both this study and the considerable preliminary work necessary.
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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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U2 - 10.1016/j.jtcvs.2006.12.056
DO - 10.1016/j.jtcvs.2006.12.056
M3 - Article
C2 - 17532961
AN - SCOPUS:34249065651
SN - 0022-5223
VL - 133
SP - 1588
EP - 1596
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 6
ER -