Response of brain oxygenation and metabolism to deep hypothermic circulatory arrest in newborn piglets: comparison of pH-stat and alpha-stat strategies.
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 degrees 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.
Markowitz
Scott D
SD
Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Mendoza-Paredes
Alberto
A
Liu
Huiping
H
Pastuszko
Peter
P
Schultz
Steven P
SP
Schears
Gregory J
GJ
Greeley
William J
WJ
Wilson
David F
DF
Pastuszko
Anna
A
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood; D002315:Cardiopulmonary Bypass; D002470:Cell Survival; D050792:Circulatory Arrest, Deep Hypothermia Induced; D003342:Corpus Striatum / Q000737:chemistry; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004298:Dopamine / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013552:Swine; D051028:bcl-2-Associated X Protein / Q000032:analysis
D017362:Cyclic AMP Response Element-Binding Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002245:Carbon Dioxide; D010100:Oxygen; D004298:Dopamine