PMID- 23717659
OWN - NLM
STAT- MEDLINE
DCOM- 20140107
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - Therapeutic hypothermia activates the endothelin and nitric oxide systems after 
      cardiac arrest in a pig model of cardiopulmonary resuscitation.
PG  - e64792
LID - 10.1371/journal.pone.0064792 [doi]
LID - e64792
AB  - Post-cardiac arrest myocardial dysfunction is a major cause of mortality in 
      patients receiving successful cardiopulmonary resuscitation (CPR). Mild 
      therapeutic hypothermia (MTH) is the recommended treatment after resuscitation 
      from cardiac arrest (CA) and is known to exert neuroprotective effects and 
      improve short-term survival. Yet its cytoprotective mechanisms are not fully 
      understood. In this study, our aim was to determine the possible effect of MTH on 
      vasoactive mediators belonging to the endothelin/nitric oxide axis in our porcine 
      model of CA and CPR. Pigs underwent either untreated CA or CA with subsequent 
      CPR. After state-of-the-art resuscitation, the animals were either left 
      untreated, cooled between 32-34  degrees C after ROSC or treated with a bolus injection 
      of S-PBN (sodium 4-[(tert-butylimino) methyl]benzene-3-sulfonate N-oxide) until 
      180 min after ROSC, respectively. The expression of endothelin 1 (ET-1), 
      endothelin converting enzyme 1 (ECE-1), and endothelin A and B receptors (ETAR 
      and ETBR) transcripts were measured using quantitative real-time PCR while 
      protein levels for the ETAR, ETBR and nitric oxide synthases (NOS) were assessed 
      using immunohistochemistry and Western Blot. Our results indicated that the 
      endothelin system was not upregulated at 30, 60 and 180 min after ROSC in 
      untreated postcardiac arrest syndrome. Post-resuscitative 3 hour-long treatments 
      either with MTH or S-PBN stimulated ET-1, ECE-1, ETAR and ETBR as well as 
      neuronal NOS and endothelial NOS in left ventricular cardiomyocytes. Our data 
      suggests that the endothelin and nitric oxide pathways are activated by MTH in 
      the heart.
FAU - Zoerner, Frank
AU  - Zoerner F
AD  - Department of Surgical Sciences/Anesthesiology and Intensive Care, Uppsala 
      University, Uppsala, Sweden.
FAU - Wiklund, Lars
AU  - Wiklund L
FAU - Miclescu, Adriana
AU  - Miclescu A
FAU - Martijn, Cecile
AU  - Martijn C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130523
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Benzenesulfonates)
RN  - 0 (Cardiovascular Agents)
RN  - 0 (Endothelin-1)
RN  - 0 (Receptors, Endothelin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
SB  - IM
MH  - Animals
MH  - Aspartic Acid Endopeptidases/genetics/metabolism
MH  - Benzenesulfonates/pharmacology
MH  - *Cardiopulmonary Resuscitation
MH  - Cardiovascular Agents/pharmacology
MH  - Endothelin-1/genetics/*metabolism
MH  - Gene Expression/drug effects
MH  - Gene Expression Regulation
MH  - Heart Arrest/metabolism/*therapy
MH  - *Hypothermia, Induced
MH  - Myocardial Reperfusion Injury/metabolism/prevention & control
MH  - Myocardium/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase/genetics/metabolism
MH  - Receptors, Endothelin/genetics/metabolism
MH  - Sus scrofa
PMC - PMC3662665
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/05/30 06:00
MHDA- 2014/01/08 06:00
PMCR- 2013/05/23
CRDT- 2013/05/30 06:00
PHST- 2012/07/22 00:00 [received]
PHST- 2013/04/18 00:00 [accepted]
PHST- 2013/05/30 06:00 [entrez]
PHST- 2013/05/30 06:00 [pubmed]
PHST- 2014/01/08 06:00 [medline]
PHST- 2013/05/23 00:00 [pmc-release]
AID - PONE-D-12-21956 [pii]
AID - 10.1371/journal.pone.0064792 [doi]
PST - epublish
SO  - PLoS One. 2013 May 23;8(5):e64792. doi: 10.1371/journal.pone.0064792. Print 2013.