Brain oxygen and metabolism is dependent on the rate of low-flow cardiopulmonary bypass following circulatory arrest in newborn piglets.
OBJECTIVE
To determine the optimum rate of low-flow hypothermic cardiopulmonary bypass (LF), following circulatory arrest (DHCA) on brain oxygenation (bO(2)), extracellular dopamine (DA), phosphorylation of select neuroregulatory proteins responsible for neuronal injury, and survival following ischemic brain injury: CREB, Erk1/2, Akt, Bcl-2, and Bax.


METHODS
The piglets were placed on cardiopulmonary bypass (CPB) and cooled to 18 degrees C. They were then subjected to 30 min of DHCA followed by 1h of LF at 20, 50, or 80 ml/(kg/min), rewarmed, separated from CPB, and maintained for 2h. The bO(2) was measured by quenching of phosphorescence; DA by microdialysis; phosphorylation of CREB, ERK1/2, Akt, Bcl-2, and Bax by Western blots. The results are means+/-SD for seven experiments.


RESULTS
Pre-bypass bO(2) was 47.4+/-4.2 mmHg and decreased to 1.9+/-0.8 mmHg during DHCA. At the end of LF at 20, 50, and 80 ml/(kg/min), bO(2) was 11.8+/-1.6, 26+/-1.8, and 33.9+/-2.6 mmHg, respectively. The DA increased 510-fold relative to control (p<0.001) by 15 min of LF-20 with maximum increase occurring at 45 min. With LF-50, increase in DA was not statistically significant and no increase was observed when LF-80 was used. Bcl-2 immunoreactivity increased after LF-50 and LF-80 (140+/-14.5%, p<0.05 and 202+/-34%, p<0.05, respectively). Neither flow increased Bax immunoreactivity. The ratio of Bcl-2/Bax, pCREB, pAkt, pErk increased significantly with increasing the flow rate of LF.


CONCLUSIONS
The protective effect of LF following DHCA on brain metabolism is dependent on the flow rate. Flow-dependent increase in pCREB, pErk1/2, pAkt, increase in Bcl-2/Bax, and decrease in DA indicated that to minimize DHCA-dependent neuronal injury, LF flow should be above 50 ml/(kg/min).
Pastuszko
Peter
P
Department of Surgery, The University of Oklahoma, Oklahoma City, OK, USA. peter-pastuszko@ouhsc.edu
Liu
Huiping
H
Mendoza-Paredes
Alberto
A
Schultz
Steven E
SE
Markowitz
Scott D
SD
Greeley
William J
WJ
Wilson
David F
DF
Pastuszko
Anna
A
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002315:Cardiopulmonary Bypass / Q000379:methods*; D002540:Cerebral Cortex / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000379:methods*; D003342:Corpus Striatum / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis; D015259:Dopamine Agents / Q000032:analysis; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis; D051058:Oncogene Protein v-akt / Q000032:analysis; 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; D015259:Dopamine Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051058:Oncogene Protein v-akt; D020928:Mitogen-Activated Protein Kinases; D010100:Oxygen; D004298:Dopamine