PMID- 17382626 OWN - NLM STAT- MEDLINE DCOM- 20070417 LR - 20071211 IS - 1097-685X (Electronic) IS - 0022-5223 (Linking) VI - 133 IP - 4 DP - 2007 Apr TI - Effect of profound hypothermia during circulatory arrest on neurologic injury and apoptotic repressor protein Bcl-2 expression in an acute porcine model. PG - 919-26 AB - 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. FAU - Ananiadou, Olga G AU - Ananiadou OG AD - Department of Cardiac Surgery, University of Ioannina, School of Medicine, Ioannina, Greece. oananiadou@yahoo.co.uk FAU - Bibou, Katherine AU - Bibou K FAU - Drossos, George E AU - Drossos GE FAU - Charchanti, Antonia AU - Charchanti A FAU - Bai, Mary AU - Bai M FAU - Haj-Yahia, Saleem AU - Haj-Yahia S FAU - Anagnostopoulos, Constantine E AU - Anagnostopoulos CE FAU - Johnson, Elizabeth O AU - Johnson EO LA - eng PT - Journal Article DEP - 20070222 PL - United States TA - J Thorac Cardiovasc Surg JT - The Journal of thoracic and cardiovascular surgery JID - 0376343 RN - 0 (Proto-Oncogene Proteins c-bcl-2) SB - IM CIN - J Thorac Cardiovasc Surg. 2007 Nov;134(5):1381-2; author reply 1382-3. PMID: 17976495 MH - Animals MH - Apoptosis/physiology MH - Brain Diseases/etiology/*metabolism MH - Cardiopulmonary Bypass/adverse effects MH - Circulatory Arrest, Deep Hypothermia Induced/*adverse effects MH - Disease Models, Animal MH - Hippocampus/physiopathology MH - Hypothermia, Induced/adverse effects MH - In Situ Nick-End Labeling MH - Male MH - Neocortex/physiopathology MH - Proto-Oncogene Proteins c-bcl-2/*biosynthesis MH - Swine EDAT- 2007/03/27 09:00 MHDA- 2007/04/18 09:00 CRDT- 2007/03/27 09:00 PHST- 2006/04/19 00:00 [received] PHST- 2006/09/25 00:00 [revised] PHST- 2006/10/09 00:00 [accepted] PHST- 2007/03/27 09:00 [pubmed] PHST- 2007/04/18 09:00 [medline] PHST- 2007/03/27 09:00 [entrez] AID - S0022-5223(06)02086-1 [pii] AID - 10.1016/j.jtcvs.2006.10.045 [doi] PST - ppublish SO - J Thorac Cardiovasc Surg. 2007 Apr;133(4):919-26. doi: 10.1016/j.jtcvs.2006.10.045. Epub 2007 Feb 22.