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J Thorac Cardiovasc Surg 2007;133:1588-1596
© 2007 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

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

^a Department of Pediatric Cardiac Surgery, Oregon Health Sciences University, Portland, Ore
^b Department of Neuropathology, Oregon Health Sciences University, Portland, Ore
^c Department of Immunology, Oregon Health Sciences University, Portland, Ore.

Presented as a poster presentation at the Thirty-second Annual Meeting of the Western Thoracic Surgical Association, Sun Valley, Idaho, June 21-24, 2006.

Received for publication July 27, 2006; revisions received November 15, 2006; accepted for publication December 18, 2006.

^_* Address for reprints: Edward J. Hickey, MD, CHSS Data Center, Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. (Email: hickeydoc{at}yahoo.com).

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.