Abstract
Objective: Concern over neurologic injury limits safe duration of deep hypothermic circulatory arrest (DHCA) in surgery for congenital cardiac disease. Proteomics is a novel and powerful technique to study global protein changes in a given protein system. Using a neonatal model of cardiopulmonary bypass with DHCA, we sought to characterize the protein changes associated with DHCA brain injury. Methods: Ten neonatal piglets were randomized to cardiopulmonary bypass with DHCA or sham operation. DHCA animals underwent induction of bypass (100 mL · kg-1 · min-1), cooling to 18°C, then DHCA for 60 minutes. Animals were rewarmed to normothermia, weaned from bypass, and harvested after 30 minutes off bypass. Sham animals underwent sternotomy without further instrumentation. Plasma samples were taken before bypass and before harvest. Proteins differentially expressed in the cerebral neocortex between the 2 groups were determined by 2-dimensional differential gel electrophoresis using fluorescent cyanine dyes and mass spectrometry. A second group of 4 piglets were similarly randomized and, after the experiment, tissues underwent perfusion-fixation for histologic examination. Results: Cardiopulmonary bypass with DHCA caused extensive histologic and ultrastructural cerebral injury. Proteomic analysis of cerebral cortex found 10 protein spots to be differentially expressed; 9 were identified by mass spectrometry to represent 6 proteins, including apolipoprotein A-1, neurofilament-M protein, and enolase. Decreased expression of plasma apolipoprotein A-1 was found in DHCA. Conclusions: The acute protein changes associated with cerebral injury in a neonatal model of cardiopulmonary bypass with DHCA have been characterized. These may direct further research aimed at attenuating injury seen from cardiopulmonary bypass with DHCA.
| Original language | English (US) |
|---|---|
| Journal | Journal of Thoracic and Cardiovascular Surgery |
| Volume | 132 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Surgery
Cite this
Proteomics of cerebral injury in a neonatal model of cardiopulmonary bypass with deep hypothermic circulatory arrest. / Sheikh, Amir M.; Barrett, Cindy; Villamizar, Nestor; Alzate, Oscar; Miller, Sara; Shelburne, John; Lodge, Andrew; Lawson, Jeffrey; Jaggers, James.
In: Journal of Thoracic and Cardiovascular Surgery, Vol. 132, No. 4, 10.2006.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Proteomics of cerebral injury in a neonatal model of cardiopulmonary bypass with deep hypothermic circulatory arrest
AU - Sheikh, Amir M.
AU - Barrett, Cindy
AU - Villamizar, Nestor
AU - Alzate, Oscar
AU - Miller, Sara
AU - Shelburne, John
AU - Lodge, Andrew
AU - Lawson, Jeffrey
AU - Jaggers, James
PY - 2006/10
Y1 - 2006/10
N2 - Objective: Concern over neurologic injury limits safe duration of deep hypothermic circulatory arrest (DHCA) in surgery for congenital cardiac disease. Proteomics is a novel and powerful technique to study global protein changes in a given protein system. Using a neonatal model of cardiopulmonary bypass with DHCA, we sought to characterize the protein changes associated with DHCA brain injury. Methods: Ten neonatal piglets were randomized to cardiopulmonary bypass with DHCA or sham operation. DHCA animals underwent induction of bypass (100 mL · kg-1 · min-1), cooling to 18°C, then DHCA for 60 minutes. Animals were rewarmed to normothermia, weaned from bypass, and harvested after 30 minutes off bypass. Sham animals underwent sternotomy without further instrumentation. Plasma samples were taken before bypass and before harvest. Proteins differentially expressed in the cerebral neocortex between the 2 groups were determined by 2-dimensional differential gel electrophoresis using fluorescent cyanine dyes and mass spectrometry. A second group of 4 piglets were similarly randomized and, after the experiment, tissues underwent perfusion-fixation for histologic examination. Results: Cardiopulmonary bypass with DHCA caused extensive histologic and ultrastructural cerebral injury. Proteomic analysis of cerebral cortex found 10 protein spots to be differentially expressed; 9 were identified by mass spectrometry to represent 6 proteins, including apolipoprotein A-1, neurofilament-M protein, and enolase. Decreased expression of plasma apolipoprotein A-1 was found in DHCA. Conclusions: The acute protein changes associated with cerebral injury in a neonatal model of cardiopulmonary bypass with DHCA have been characterized. These may direct further research aimed at attenuating injury seen from cardiopulmonary bypass with DHCA.
AB - Objective: Concern over neurologic injury limits safe duration of deep hypothermic circulatory arrest (DHCA) in surgery for congenital cardiac disease. Proteomics is a novel and powerful technique to study global protein changes in a given protein system. Using a neonatal model of cardiopulmonary bypass with DHCA, we sought to characterize the protein changes associated with DHCA brain injury. Methods: Ten neonatal piglets were randomized to cardiopulmonary bypass with DHCA or sham operation. DHCA animals underwent induction of bypass (100 mL · kg-1 · min-1), cooling to 18°C, then DHCA for 60 minutes. Animals were rewarmed to normothermia, weaned from bypass, and harvested after 30 minutes off bypass. Sham animals underwent sternotomy without further instrumentation. Plasma samples were taken before bypass and before harvest. Proteins differentially expressed in the cerebral neocortex between the 2 groups were determined by 2-dimensional differential gel electrophoresis using fluorescent cyanine dyes and mass spectrometry. A second group of 4 piglets were similarly randomized and, after the experiment, tissues underwent perfusion-fixation for histologic examination. Results: Cardiopulmonary bypass with DHCA caused extensive histologic and ultrastructural cerebral injury. Proteomic analysis of cerebral cortex found 10 protein spots to be differentially expressed; 9 were identified by mass spectrometry to represent 6 proteins, including apolipoprotein A-1, neurofilament-M protein, and enolase. Decreased expression of plasma apolipoprotein A-1 was found in DHCA. Conclusions: The acute protein changes associated with cerebral injury in a neonatal model of cardiopulmonary bypass with DHCA have been characterized. These may direct further research aimed at attenuating injury seen from cardiopulmonary bypass with DHCA.
UR - http://www.scopus.com/inward/record.url?scp=33748776575&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748776575&partnerID=8YFLogxK
U2 - 10.1016/j.jtcvs.2006.07.002
DO - 10.1016/j.jtcvs.2006.07.002
M3 - Article
C2 - 17000293
AN - SCOPUS:33748776575
VL - 132
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
SN - 0022-5223
IS - 4
ER -