title: Effect of profound hypothermia during circulatory arrest on neurologic injury and apoptotic repressor protein Bcl-2 expression in an acute porcine model.
abstract: OBJECTIVE
  We reported that the neocortex and hippocampus are selectively vulnerable to injury in an acute porcine model of hypothermic circulatory arrest at 18 degrees C. We hypothesize that further cooling to 10 degrees C could reduce neurologic injury in these regions. To further elucidate the mechanisms of neurologic injury and protection, we assessed the expression of the anti-apoptotic protein Bcl-2.
  
  
  METHODS
  Twelve piglets underwent 75 minutes of hypothermic circulatory arrest at 18 degrees C (n = 6) and 10 degrees C (n = 6). After gradual rewarming and reperfusion, animals were put to death and brains were perfusion-fixed and cryopreserved. Regional patterns of neuronal apoptosis after hypothermic circulatory arrest were characterized by in situ DNA fragmentation with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) histochemistry. Bcl-2 protein expression was characterized with immunohistochemistry. Statistical comparisons were made by t test, analysis of variance, and Mann-Whitney U test, as appropriate.
  
  
  RESULTS
  Concentrations of TUNEL(+) cells were significantly lower after profound hypothermia at 10 degrees C compared with 18 degrees C hypothermia in the sensory and motor neocortex and hippocampus (t test, P < .0001; P < .006; P < .006, respectively). Positive Bcl-2 immunostaining was observed only in the motor and sensory neocortex and hippocampus after 18 degrees C hypothermic circulatory arrest. Profound cooling to 10 degrees C resulted in a significant increase in Bcl-2 immunostaining in the motor and sensory cortex as compared with 18 degrees C (Mann-Whitney U test, P < .05).
  
  
  CONCLUSIONS
  Deep hypothermia at 10 degrees C protects the neocortex and hippocampus from insult during hypothermic circulatory arrest as suggested by significantly reduced TUNEL(+) staining in these areas. Although a concomitant increase in Bcl-2 expression was observed in the neocortex at 10 degrees C, it remains unclear whether profound hypothermia deters from neuronal injury by activation of the anti-apoptotic protein Bcl-2.
authors: Department of Cardiac Surgery, University of Ioannina, School of Medicine, Ioannina, Greece. oananiadou@yahoo.co.uk
authors: Olga G
authors: OG
authors: Ananiadou
authors: Katherine
authors: K
authors: Bibou
authors: George E
authors: GE
authors: Drossos
authors: Antonia
authors: A
authors: Charchanti
authors: Mary
authors: M
authors: Bai
authors: Saleem
authors: S
authors: Haj-Yahia
authors: Constantine E
authors: CE
authors: Anagnostopoulos
authors: Elizabeth O
authors: EO
authors: Johnson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001927:Brain Diseases / Q000209:etiology / Q000378:metabolism*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000503:physiopathology; D007036:Hypothermia, Induced / Q000009:adverse effects; D020287:In Situ Nick-End Labeling; D008297:Male; D019579:Neocortex / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013552:Swine
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2