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Endotoxin preconditioning induces robust protection against brain injury resulting from deep hypothermic circulatory arrest.
E. J. Hickey, J. You, V. Kaimaktchiev, M. Stenzel-Poore, R. M. Ungerleider*. Oregon Health Sciences University, Portland, OR,
BACKGROUND:
Delayed preconditioning genetically reprograms the response to ischemic injury. Subclinical bacterial endotoxin (ET) acts through preconditioning, powerfully protecting against experimental stroke. We investigated the potential for ET to protect against cardiopulmonary bypass (CPB) related brain injury.
METHODS:
Neonatal piglets were blindly and randomly preconditioned with ET (n=6) or saline (n=6). Three days later, they experienced 2hrs hypothermic circulatory arrest (HCA) before being weaned and supported anesthetized for 20hrs in an intensive care setting. Controls included CPB without HCA (n=3) and no CPB (n=3). Brain injury was quantified using light and fluorescent microscpy (Fluoro-Jade).
RESULTS:
All animals were clinically indistinguishable before surgery. Peri- and post-operative parameters between experimental groups were similar. No control animal scored falsely positive. Histological scores were 0.33±0.21, 0.66±0.42 and 0.5±0.24 in the cortex(COR), basal ganglia(BG) and hippocampus(HC) respectively, in the ET animals but significantly worse in all saline animals (1.33±0.21(p<0.01); 1.66±0.33,(p=0.09); and 6.0±1.5,(p<0.01)). Two ET brains were histologically indistinguishable from controls.
CONCLUSIONS:
This is the first report of successful delayed preconditioning against CPB brain injury. Because ET preconditioning is a systemic phenomenon offering proven protection against myocardial, hepatic and pulmonary injury, this technique offers enormous potential for protecting against systemic neonatal CPB-injury.  
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