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Eur J Cardiothorac Surg 2006;29:168-174
© 2006 Elsevier Science NL
a Department of Anesthesiology and Critical Care, Mayo Clinic, Rochester, MN, USA
b Department of Biochemistry and Biophysics, University of Pennsylvania, School of Medicine, 901 Stellar-Chance Bldg., Philadelphia, PA 19104, USA
c Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, PA 19104, USA
Received 31 March 2005; received in revised form 29 September 2005; accepted 3 November 2005.
* Corresponding author. Tel.: +1 215 898 6382; fax: +1 215 573 3787. (Email: pastuszk{at}mail.med.upenn.edu).
Objective: To investigate the possible neuroprotective effects of selective cerebral perfusion (SCP) during deep hypothermic circulatory arrest on brain oxygenation and metabolism in newborn piglets. Methods: Newborn piglets 24 days of age, anesthetized and mechanically ventilated, were used for the study. The animals were placed on cardiopulmonary bypass, cooled to 18 °C and put on SCP (20 ml/(kg min)) for 90 min. After rewarming, the animals were monitored through 2 h of recovery. Oxygen pressure in the microvasculature of the cortex was measured by oxygen-dependent quenching of phosphorescence. The extracellular level of dopamine in striatum was measured by microdialysis and hydroxyl radicals by ortho-tyrosine levels. Levels of phosphorylated cAMP response element binding protein (pCREB) in striatal tissue were measured by Western blots using antibodies specific for phosphorylated CREB.
The results are presented as mean ± SD (p < 0.05 was significant). Results: Pre-bypass cortical oxygen pressure was 48.9 ± 11.3 mmHg and during the first 5 min of SCP, the peak of the histogram, corrected to 18 °C, decreased to 11.2 ± 3.8 mmHg (p < 0.001) and stayed near that value to the end of bypass. The mean value for the peak of the histograms measured at the end of SCP was 8 ± 3 mmHg (p < 0.001). SCP completely prevented the deep hypothermic circulatory arrest-dependent increase in extracellular dopamine and hydroxyl radicals. After SCP, there was a statistically significant increase in pCREB immunoreactivity (534 ± 60%) compared to the sham-operated group (100 ± 63%, p < 0.005). Measurements of total CREB showed that SCP did induce a statistically significant increase in CREB as compared to sham-operated animals (168 ± 31%, p < 0.05). Conclusion: SCP, as compared to DHCA, improved cortical oxygenation and prevented increases in the extracellular dopamine and hydroxyl radicals. The increase in pCREB in the striatum following SCP may contribute to improved cellular recovery after this procedure.
Key Words: Selective cerebral perfusion Brain oxygenation Dopamine Hydroxyl radicals cAMP response element binding protein
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