title: Proteomics of cerebral injury in a neonatal model of cardiopulmonary bypass with deep hypothermic circulatory arrest.
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 x kg(-1) x min(-1)), cooling to 18 degrees 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.
authors.affiliation: Department of Pediatric Cardiac Surgery, the Neuroproteomics Center, Duke University Medical Center, Durham, NC, USA. amsheikh10@hotmail.com
authors.forename: Amir M
authors.initials: AM
authors.lastname: Sheikh
authors.forename: Cindy
authors.initials: C
authors.lastname: Barrett
authors.forename: Nestor
authors.initials: N
authors.lastname: Villamizar
authors.forename: Oscar
authors.initials: O
authors.lastname: Alzate
authors.forename: Sara
authors.initials: S
authors.lastname: Miller
authors.forename: John
authors.initials: J
authors.lastname: Shelburne
authors.forename: Andrew
authors.initials: A
authors.lastname: Lodge
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lawson
authors.forename: James
authors.initials: J
authors.lastname: Jaggers
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry; D001930:Brain Injuries / Q000378:metabolism*; D002315:Cardiopulmonary Bypass; D050792:Circulatory Arrest, Deep Hypothermia Induced; D011506:Proteins / Q000032:analysis; D040901:Proteomics; D013552:Swine
chemical_list: D011506:Proteins