Cardioprotection Is Alive But Remains Enigmatic

Abstract

Article, see p 2337… the report of my death was an exaggeration.—Mark Twain, 1897The translation of cardioprotection to clinical practice has been disappointing so far.1,2 Lefer and Marban3 have even questioned whether cardioprotection is still alive because there is at present, after >30 years of intense investigation,4 no phase III trial with improved clinical outcome after a cardioprotective intervention.However, this provocative question appears exaggerated. In fact, there are a number of promising clinical proof-of-concept trials on cardioprotection with surrogate end points, notably infarct size by biomarkers and imaging,5 and the existing neutral or negative clinical outcome trials have major conceptual and methodological problems.6 The biggest problem in the field of cardioprotection, however, is our limited mechanistic understanding, despite literally thousands of experimental studies on its molecular signaling mechanisms.7Almost 10 years ago, I wrote an editorial for Circulation on cardioprotection that focused on nitric oxide, protein kinases, and mitochondria.8 It seems that we have not progressed much further in our understanding of cardioprotection but only in detail. Nitric oxide activates guanylate cyclase to increase cyclic guanosine monophosphate formation as well as …