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Ouabain—The Key to Cardioprotection?

Based on a wealth of mechanistic evidence supported by the fact that ouabain mimics the spleen–liver effect in this article, the hypothesis is established that the endogenous hormone ouabain not only mimics the effects of ischemic preconditioning but also may be an ideal drug for the prevention of ischemic diseases. Moreover, it is argued that the spleen–liver effect may represent a general protective mechanism for the protection of organisms against oxygen deficiency. Investigating the spleen–liver mechanism offers a new approach to decipher the secrets of ischemic conditioning. Preconditioning represents a basic mechanism to protect a wide variety of cells against stressful stimuli such as ischemia. The ability to undergo preconditioning is almost ubiquitous in tissues and is highly conserved across species. Reinvestigation of the “spleen–liver mechanism” will allow the study of metabolic inhibitors and hormone mimics that all could help to transform ischemic preconditioning into a cure of the epidemic ischemic heart disease. Ouabain mimics the effects of the spleen factor. Cardioprotection induced by ouabain is due to the activation of pathways that are also activated in ischemic preconditioning. Just like ischemic preconditioning, ouabain activates the reperfusion injury salvage kinase pathway. Activation of nuclear factor kappa B and other transcription factors contribute to the long lasting effects of ouabain. The endogenous hormone ouabain just like preconditioning offers multiorgan protection based on innate mechanisms, which warrants clinical investigation. Clinical studies with ouabain that correspond to current standards are warranted.