In patients with acute
myocardial infarction, timely reperfusion is essential to limit
infarct size. However, reperfusion also adds to myocardial injury. Brief episodes of ischaemia/reperfusion in the myocardium or on organ remote from the heart, before or shortly after sustained myocardial ischaemia effectively reduce
infarct size, provided there is eventual reperfusion. Such conditioning phenomena have been established in many experimental studies and also translated to humans. The underlying signal transduction, that is the molecular identity of triggers, mediators and effectors, is not clear yet in detail, but several extracellular signalling molecules, such as
adenosine,
bradykinin and
opioids, have been identified to contribute to cardioprotection by conditioning manoeuvres. Several trials have attempted the translation of cardioprotection by such
autacoids into a clinical scenario of myocardial ischaemia and reperfusion.
Adenosine and its selective agonists reduced
infarct size in a few studies, but this benefit was not translated into improved clinical outcome. All studies with
bradykinin or drugs which increase
bradykinin's bioavailability reported reduced
infarct size and some of them also improved clinical outcome. Synthetic
opioid agonists did not result in a robust
infarct size reduction, but this failure of translation may relate to the cardioprotective properties of the underlying anaesthesia per se or of the comparator drugs. The translation of findings in healthy, young animals with acute
coronary occlusion/reperfusion to patients of older age, with a variety of co-morbidities and co-medications, suffering from different scenarios of myocardial ischaemia/reperfusion remains a challenge.