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

Abstract

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. 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). 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. 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.