Cardioprotection research must leave its comfort zone

The translation from mechanistic, more reductionist basic science research to clinical outcome studies is not a linear, rational process but fraught with many surprises such that the prediction of a clinically meaningful endpoint even from a robust preclinical endpoint is difficult. Such translational gap is not genuine for the field of cardioprotection, but particularly prominent here since there are literally thousands of basic science studies on cardioprotective interventions, drugs and signalling mechanisms but just one phase III trial with improved clinical outcome as primary endpoint.1 In the more robust experimental studies, cardioprotection has been evidenced as a reduction of infarct size following a protocol of transmural myocardial ischaemia and reperfusion, and infarct size has been—in line with solid pathophysiology—normalized for the ischaemic area at risk, without or with additional consideration of residual collateral blood flow. In clinical trials, benefit from adjunct cardioprotection in patients with acute myocardial infarction is measured by reduced MACE rate after months to years of follow-up.2 The discrepancy of success when viewed from an experimental vs. a clinical perspective is therefore obvious and the lack of translation accordingly not so surprising.3 How can we do better? I approach this question from the experimentalist’s view: