Neglect of the coronary circulation: some critical remarks on problems in the translation of cardioprotection

摘要: Acute myocardial infarction remains a significant health problem throughout the world, and for those patients surviving immediate event, infarct size is main determinant of further prognosis.1–3 Timely reperfusion, as originally reported in dogs by John Ross Jr over 30 years ago,4–6 still only way to reduce ultimate but comes also at price induces injury itself.7,8 Ischaemic preconditioning ischaemic postconditioning, again both dogs,9,10 size—provided there reperfusion!—in all species tested so far, including man.11–15 Although phenomena pre- postconditioning have stimulated research on pathobiology ischaemia reperfusion general, notably endogenous protective signalling mechanisms,12,16 their value has thus far remained mostly paradigmatic. The translation experimental findings with acute somewhat inferential preconditioning11 been limited small-scale proof-of-concept studies highly selected patients17,18 or retrospective analyses19 not yet successful therapeutic reality. Obvious problems cardioprotection from experiment clinic critically reviewed before,13–15,20 choice model mimic human situation, potentially cardioprotective molecule/drug, design clinical trial respect dose time treatment, selection size, site collateralization infarcting myocardium, age,21 co-morbidities, co-treatments.22 Surprisingly, coronary circulation, which culprit infarction, neglected potential …