PMID- 19767525
OWN - NLM
STAT- MEDLINE
DCOM- 20091112
LR  - 20211020
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 297
IP  - 5
DP  - 2009 Nov
TI  - Pyruvate-fortified cardioplegia evokes myocardial erythropoietin signaling in 
      swine undergoing cardiopulmonary bypass.
PG  - H1914-22
LID - 10.1152/ajpheart.01213.2008 [doi]
AB  - Pyruvate-fortified cardioplegia protects myocardium and hastens postsurgical 
      recovery of patients undergoing cardiopulmonary bypass (CPB). Pyruvate reportedly 
      suppresses degradation of the alpha-subunit of hypoxia-inducible factor-1 
      (HIF-1), an activator of the gene encoding the cardioprotective cytokine 
      erythropoietin (EPO). This study tested the hypothesis that pyruvate-enriched 
      cardioplegia evoked EPO expression and mobilized EPO signaling mechanisms in 
      myocardium. Hearts of pigs maintained on CPB were arrested for 60 min with 4:1 
      blood-crystalloid cardioplegia. The crystalloid component contained 188 mM 
      glucose + or - 24 mM pyruvate. After 30-min cardiac reperfusion with 
      cardioplegia-free blood, the pigs were weaned from CPB. Left ventricular 
      myocardium was sampled 4 h after CPB for immunoblot assessment of HIF-1alpha, EPO 
      and its receptor, the signaling kinases Akt and ERK, and endothelial nitric oxide 
      synthase (eNOS), an effector of EPO signaling. Pyruvate-fortified cardioplegia 
      stabilized arterial pressure post-CPB, induced myocardial EPO mRNA expression, 
      and increased HIF-1alpha, EPO, and EPO-R protein contents by 60, 58, and 123%, 
      respectively, vs. control cardioplegia (P < 0.05). Pyruvate cardioplegia also 
      increased ERK phosphorylation by 61 and 118%, respectively, vs. control 
      cardioplegia-treated and non-CPB sham myocardium (P < 0.01), but did not alter 
      Akt phosphorylation. Nitric oxide synthase (NOS) activity and eNOS content fell 
      32% following control CPB vs. sham, but pyruvate cardioplegia prevented these 
      declines, yielding 49 and 80% greater NOS activity and eNOS content vs. 
      respective control values (P < 0.01). Pyruvate-fortified cardioplegia induced 
      myocardial EPO expression and mobilized the EPO-ERK-eNOS mechanism. By 
      stabilizing HIF-1alpha, pyruvate-fortified cardioplegia may evoke sustained 
      activation of EPO's cardioprotective signaling cascade in myocardium.
FAU - Ryou, Myoung-Gwi
AU  - Ryou MG
AD  - Department of Integrative Physiology, University of North Texas, Health Science 
      Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA.
FAU - Flaherty, Devin C
AU  - Flaherty DC
FAU - Hoxha, Besim
AU  - Hoxha B
FAU - Sun, Jie
AU  - Sun J
FAU - Gurji, Hunaid
AU  - Gurji H
FAU - Rodriguez, Steven
AU  - Rodriguez S
FAU - Bell, Glenn
AU  - Bell G
FAU - Olivencia-Yurvati, Albert H
AU  - Olivencia-Yurvati AH
FAU - Mallet, Robert T
AU  - Mallet RT
LA  - eng
GR  - HL-71684/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090918
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Cardioplegic Solutions)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Erythropoietin)
RN  - 11096-26-7 (Erythropoietin)
RN  - 8558G7RUTR (Pyruvic Acid)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Cardioplegic Solutions/metabolism/*pharmacology
MH  - *Cardiopulmonary Bypass/adverse effects
MH  - Edema, Cardiac/etiology/metabolism/prevention & control
MH  - Energy Metabolism
MH  - Erythropoietin/genetics/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Glutathione/metabolism
MH  - Heart Arrest, Induced/adverse effects/*methods
MH  - Heart Diseases/etiology/metabolism/physiopathology/*prevention & control
MH  - Heart Rate/drug effects
MH  - Heart Ventricles/drug effects/metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Male
MH  - Models, Animal
MH  - Myocardium/*metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Oxidation-Reduction
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pyruvic Acid/metabolism/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Erythropoietin/metabolism
MH  - Signal Transduction/*drug effects
MH  - Swine
MH  - Time Factors
MH  - Up-Regulation
PMC - PMC2781381
EDAT- 2009/09/22 06:00
MHDA- 2009/11/13 06:00
PMCR- 2010/11/01
CRDT- 2009/09/22 06:00
PHST- 2009/09/22 06:00 [entrez]
PHST- 2009/09/22 06:00 [pubmed]
PHST- 2009/11/13 06:00 [medline]
PHST- 2010/11/01 00:00 [pmc-release]
AID - 01213.2008 [pii]
AID - H-01213-2008 [pii]
AID - 10.1152/ajpheart.01213.2008 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1914-22. doi: 
      10.1152/ajpheart.01213.2008. Epub 2009 Sep 18.