Combined sphingosine, S1P and ischemic postconditioning rescue the heart after protracted ischemia.

Biochemical and Biophysical Research Communications
Donald A VesseyJoel S Karliner

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.

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Citations

Jun 23, 2009·Basic Research in Cardiology·Andreas SkyschallyGerd Heusch
Aug 4, 2010·Basic Research in Cardiology·Lydia LacerdaSandrine Lecour
Mar 7, 2012·Cardiovascular Drugs and Therapy·Sarin J SomersSandrine Lecour
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Nov 20, 2008·Cardiovascular Research·Joel S Karliner
Mar 14, 2009·Cardiovascular Research·Christopher K Means, Joan Heller Brown
Aug 12, 2009·Cardiovascular Research·Lydia LacerdaSandrine Lecour
Feb 28, 2009·Journal of Cardiovascular Pharmacology·Joel S Karliner
May 13, 2009·Journal of Cardiovascular Pharmacology·Rong TaoJoel S Karliner
Aug 4, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Donald A VesseyJoel S Karliner
Jun 28, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Emmanuel Eroume A EgomMing Lei
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Mar 28, 2021·Nature Reviews. Cardiology·Ran Hee ChoiWilliam L Holland

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