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

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 133; no. 6; pp. 1588 - 1596
• Main Authors: Hickey, Edward J., MRCS, You, Xiaomang, MD, Kaimaktchiev, Vassil, MD, Stenzel-Poore, Mary, PhD, Ungerleider, Ross M., MD
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Mosby, Inc 01.06.2007; AATS/WTSA; Elsevier
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Brain Injuries - pathology; Brain Injuries - prevention & control; Cardiothoracic Surgery; Circulatory Arrest, Deep Hypothermia Induced; Ischemic Preconditioning - methods; Lipopolysaccharides - pharmacology; Medical sciences; Microscopy, Fluorescence; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Swine; 25; 19; deep hypothermic circulatory arrest; TNF; LPS; CPB; tumor necrosis factor; cardiopulmonary bypass; TLR; lipopolysaccharide; DHCA; 20; Toll-like receptor; 21; Heart; Brain; Prisoner; Carceral environment; Arrest; Injury; Thorax; Trauma; Encephalon; Treatment; Surgery; Legal aspect; Lipopolysaccharide; Lesion; Protection; Preconditioning
• ISSN: 0022-5223; 1097-685X
• DOI: 10.1016/j.jtcvs.2006.12.056

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.