PMID- 16731130
OWN - NLM
STAT- MEDLINE
DCOM- 20070927
LR  - 20161124
IS  - 1552-6259 (Electronic)
IS  - 0003-4975 (Linking)
VI  - 81
IP  - 6
DP  - 2006 Jun
TI  - Thoracic Surgery Directors Association Award. Cobalt chloride pretreatment 
      attenuates myocardial apoptosis after hypothermic circulatory arrest.
PG  - 2055-62; discussion 2062
AB  - BACKGROUND: Deep hypothermic circulatory arrest (DHCA) causes myocyte injury as a 
      consequence of ischemia and reperfusion. Previous studies have shown that hypoxia 
      or hypoxia-mimetic agents (cobalt chloride [CoCl2] or deferoxamine [DFX]) limit 
      myocyte necrosis by upregulating the transcription factor hypoxia-inducible 
      factor. However, it remains unknown whether these agents attenuate myocardial 
      apoptosis after DHCA. This study tested the hypotheses (1) that hypoxia, DFX, or 
      CoCl2 preconditioning attenuates myocardial apoptosis during DHCA; and (2) that 
      the protective mechanism involves the altered expression of apoptosis regulatory 
      proteins pAkt (antiapoptotic), Bcl-2 (antiapoptotic), and Bax (proapoptotic). 
      METHODS: Anesthetized neonatal piglets were randomly assigned to four groups (n = 
      6 in a group): control (NaCl injection); hypoxia (pO2 of 30 to 40 mm Hg for 3 
      hours); DFX injection; or CoCl2 injection. Twenty-four hours later, the animals 
      underwent cardiopulmonary bypass (CPB) and 110 minutes of DHCA. One week after 
      CPB, percentage of apoptotic myocytes (terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling [TUNEL] assay) and expression of the 
      pAKT, Bcl-2, and Bax were assessed by Western blot. RESULTS: Although 
      preconditioning with hypoxia and DFX failed to show a protective benefit, CoCl2 
      pretreatment significantly attenuated myocardial apoptosis (9.3% +/- 4.1%) versus 
      controls (33.8% +/- 9.7%, p = 0.042). That was associated with increased 
      myocardial pAkt expression (0.19 +/- 0.006 in CoCl2 versus 0.12 +/- 0.008 in 
      control, p < 0.001). The expression of Bcl-2 was also significantly higher in the 
      CoCl2 group (0.15 +/- 0.02) versus control (0.11 +/- 0.01, p = 0.007), whereas 
      Bax expression was lower (0.34 +/- 0.04 versus 0.54 +/- 0.03 for control, p < 
      0.001). CONCLUSIONS: Preconditioning with CoCl2 before prolonged DHCA in neonatal 
      piglets attenuates myocardial apoptosis by mechanisms involving phosphorylation 
      of Akt, upregulation of the antiapoptotic protein Bcl-2, and decreased expression 
      of the proapoptotic protein Bax.
FAU - Kerendi, Faraz
AU  - Kerendi F
AD  - Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University 
      School of Medicine, Atlanta, Georgia, USA.
FAU - Kirshbom, Paul M
AU  - Kirshbom PM
FAU - Halkos, Michael E
AU  - Halkos ME
FAU - Wang, Ning-Ping
AU  - Wang NP
FAU - Kin, Hajime
AU  - Kin H
FAU - Jiang, Rong
AU  - Jiang R
FAU - Zhao, Zhi-Qing
AU  - Zhao ZQ
FAU - Kanter, Kirk R
AU  - Kanter KR
FAU - Guyton, Robert A
AU  - Guyton RA
FAU - Vinten-Johansen, Jakob
AU  - Vinten-Johansen J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Netherlands
TA  - Ann Thorac Surg
JT  - The Annals of thoracic surgery
JID - 15030100R
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 3G0H8C9362 (Cobalt)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EVS87XF13W (cobaltous chloride)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/*drug effects/genetics
MH  - Apoptosis Regulatory Proteins/*biosynthesis/genetics
MH  - Awards and Prizes
MH  - Blotting, Western
MH  - Cardiopulmonary Bypass/adverse effects
MH  - Circulatory Arrest, Deep Hypothermia Induced/*adverse effects
MH  - Cobalt/administration & dosage/*therapeutic use
MH  - DNA Fragmentation
MH  - Deferoxamine/administration & dosage/therapeutic use
MH  - Gene Expression Regulation/drug effects
MH  - Genes, bcl-2
MH  - Heart/*drug effects
MH  - Hypoxia/complications
MH  - Hypoxia-Inducible Factor 1/biosynthesis/genetics
MH  - In Situ Nick-End Labeling
MH  - Ischemic Preconditioning, Myocardial/*methods
MH  - Myocardium/metabolism/*pathology
MH  - Phosphorylation
MH  - *Preanesthetic Medication
MH  - Protein Processing, Post-Translational
MH  - Proto-Oncogene Proteins c-akt/biosynthesis/genetics
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis/genetics
MH  - Random Allocation
MH  - Sus scrofa
MH  - Thoracic Surgery
MH  - United States
MH  - bcl-2-Associated X Protein/biosynthesis/genetics
EDAT- 2006/05/30 09:00
MHDA- 2007/09/28 09:00
CRDT- 2006/05/30 09:00
PHST- 2005/01/26 00:00 [received]
PHST- 2005/12/30 00:00 [revised]
PHST- 2006/01/04 00:00 [accepted]
PHST- 2006/05/30 09:00 [pubmed]
PHST- 2007/09/28 09:00 [medline]
PHST- 2006/05/30 09:00 [entrez]
AID - S0003-4975(06)00136-6 [pii]
AID - 10.1016/j.athoracsur.2006.01.059 [doi]
PST - ppublish
SO  - Ann Thorac Surg. 2006 Jun;81(6):2055-62; discussion 2062. doi: 
      10.1016/j.athoracsur.2006.01.059.