Document Detail


Combined sphingosine, S1P and ischemic postconditioning rescue the heart after protracted ischemia.
MedLine Citation:
PMID:  18706887     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Both sphingosine and sphingosine-1-phosphate (S1P) were able to protect the ex vivo rat heart from ischemia reperfusion injury when added to the perfusion medium at the time of reperfusion after a 40min ischemia (postconditioning). Inhibitor studies revealed distinct mechanisms of protection, with S1P employing a G-protein coupled receptor pathway and sphingosine a cyclic nucleotide dependent protein kinase pathway. However, both restored ischemia-induced depletion of phospho-AKT. Extending the ischemia to 75min reduced protection by both S1P and sphingosine, but protection could be enhanced by employing them in combination. Extending the time of ischemia further to 90min almost eliminated cardioprotection by S1P or sphingosine; and their combination gave only modest protection. However, when S1P plus sphingosine was combined with a novel ramped ischemic postconditioning regimen, left ventricle developed pressure recovered by 66% and there was only a 6% infarct size. The data indicate that detrimental changes are accumulating during protracted ischemia but for up to 90min this damage is not irreversible and hearts can still recover with proper treatment.
Authors:
Donald A Vessey; Luyi Li; Michael Kelley; Joel S Karliner
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-08-14
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  375     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-11     Completed Date:  2008-09-29     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  425-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiotonic Agents / pharmacology*
Coronary Vessels / drug effects,  physiopathology
Heart Ventricles / drug effects*,  metabolism,  physiopathology*
Lysophospholipids / pharmacology*
Phosphorylation
Proto-Oncogene Proteins c-akt / antagonists & inhibitors,  metabolism
Rats
Receptors, G-Protein-Coupled / metabolism
Reperfusion Injury / metabolism,  physiopathology*
Signal Transduction / drug effects
Sphingosine / analogs & derivatives*,  pharmacology*
Grant Support
ID/Acronym/Agency:
1P01 HL68738/HL/NHLBI NIH HHS; P01 HL068738/HL/NHLBI NIH HHS; P01 HL068738-05/HL/NHLBI NIH HHS; R01 HL090606/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Lysophospholipids; 0/Receptors, G-Protein-Coupled; 26993-30-6/sphingosine 1-phosphate; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; NGZ37HRE42/Sphingosine
Comments/Corrections

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