Abstract
Ischaemic preconditioning limits the damage induced by subsequent ischaemia/reperfusion (I/R). However, preconditioning is of little practical use as the onset of an infarction is usually unpredictable. Recently, it has been shown that the heart can be protected against the extension of I/R injury if brief (10-30 sec.) coronary occlusions are performed just at the beginning of the reperfusion. This procedure has been called postconditioning (PostC). It can also be elicited at a distant organ, termed remote PostC, by intermittent pacing (dyssynchrony-induced PostC) and by pharmacological interventions, that is pharmacological PostC. In particular, brief applications of intermittent bradykinin or diazoxide at the beginning of reperfusion reproduce PostC protection. PostC reduces the reperfusion-induced injury, blunts oxidant-mediated damages and attenuates the local inflammatory response to reperfusion. PostC induces a reduction of infarct size, apoptosis, endothelial dysfunction and activation, neutrophil adherence and arrhythmias. Whether it reduces stunning is not clear yet. Similar to preconditioning, PostC triggers signalling pathways and activates effectors implicated in other cardioprotective manoeuvres. Adenosine and bradykinin are involved in PostC triggering. PostC triggers survival kinases (RISK), including Akappat and extracellular signal-regulated kinase (ERK). Nitric oxide, via nitric oxide synthase and non-enzymatic production, cyclic guanosine monophosphate (cGMP) and protein kinases G (PKG) participate in PostC. PostC-induced protection also involves an early redox-sensitive mechanism, and mitochondrial adenosine-5' -triphosphate (ATP)-sensitive K(+) and PKC activation. Protective pathways activated by PostC appear to converge on mitochondrial permeability transition pores, which are inhibited by acidosis and glycogen synthase kinase-3beta (GSK-3beta). In conclusion, the first minutes of reperfusion represent a window of opportunity for triggering the aforementioned mediators which will in concert lead to protection against reperfusion injury. Pharmacological PostC and possibly remote PostC may have a promising future in clinical scenario.