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  • Title: Effect of profound hypothermia during circulatory arrest on neurologic injury and apoptotic repressor protein Bcl-2 expression in an acute porcine model.
    Author: Ananiadou OG, Bibou K, Drossos GE, Charchanti A, Bai M, Haj-Yahia S, Anagnostopoulos CE, Johnson EO.
    Journal: J Thorac Cardiovasc Surg; 2007 Apr; 133(4):919-26. PubMed ID: 17382626.
    Abstract:
    OBJECTIVES: 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.
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