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Ann Thorac Surg 2007;84:170-176
© 2007 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Response of Brain Oxygenation and Metabolism to Deep Hypothermic Circulatory Arrest in Newborn Piglets: Comparison of pH-Stat and Alpha-Stat Strategies

^a Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
^b Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
^c Department of Surgery, University of Oklahoma, Oklahoma City, Oklahoma
^d Department of Anesthesiology, University of Miami, Miami, Florida
^e Department of Anesthesiology and Critical Care, Mayo Clinic, Rochester, Minnesota

Accepted for publication February 5, 2007.

^_* Address correspondence to Dr Pastuszko, Department of Biochemistry and Biophysics, 901 Stellar-Chance Bldg., University of Pennsylvania, Philadelphia, PA 19104 (Email: pastuszk{at}mail.med.upenn.edu).

Background: To determine the effect of pH-stat as compared with alpha-stat management on brain oxygenation, level of striatal extracellular dopamine, phosphorylation, and levels of protein kinase B (Akt) and cyclic adenosine 3’, 5’-monophosphate response element-binding protein (CREB), and levels of extracellular signal-regulated kinase (ERK)1/2, Bcl-2, and Bax in a piglet model of deep hypothermic circulatory arrest (DHCA).

Methods: The piglets were placed on cardiopulmonary bypass (CPB), cooled with pH-stat or alpha-stat to 18°C, subjected to 90 minutes of DHCA, rewarmed, weaned from CPB, and maintained for two hours recovery. The cortical oxygen was measured by: quenching of phosphorescence; dopamine by microdialysis; phosphorylation of CREB (p-CREB), ERK (p-ERK) 1/2, Akt (p-Akt), and level of Bcl-2, Bax by Western blots.

Results: Oxygen pressure histograms for the microvasculature of the cortex show substantially higher oxygen levels during cooling and during the oxygen depletion period after cardiac arrest (up to 15 minutes) when using pH-stat compared with alpha-stat management. Significant increases in dopamine occurred at 45 minutes and 60 minutes of DHCA in the alpha-stat and pH-stat groups, respectively. The p-CREB and p-Akt in the pH-stat group were significantly higher than in the alpha-stat group (140 ± 9%, p < 0.05 and 125 ± 6%, p < 0.05, respectively). There was no significant difference in p-ERK1/2 and Bax. The Bcl-2 increased in the pH-stat group to 121 ± 4% (p < 0.05) compared with the alpha-stat group. The ratio Bcl-2:Bax increased in the pH-stat group compared with the alpha-stat group.

Conclusions: The increase in p-CREB, p-Akt, Bcl-2, Bcl-2/Bax, and delay in increase of dopamine indicated that pH-stat, in the piglet model, prolongs "safe" time of DHCA and provides some brain protection against ischemic injury.