Combined sphingosine, S1P and ischemic postconditioning rescue the heart after protracted ischemia. Biochemical and biophysical research communications [Biochem Biophys Res Commun] Journal article | | Title | Combined sphingosine, S1P and ischemic postconditioning rescue the heart after protracted ischemia. | | Author(s) | Vessey DA, Li L, Kelley M, Karliner JS | | Institution | Liver Study Unit (151-K), Department of Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA; Department of Medicine, University of California, San Francisco, CA 94143, USA. | | Source | Biochem Biophys Res Commun 2008 Aug 13. | | Abstract | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18706887 |
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