ISCHEMIC AND PHARMACOLOGICAL POSTCONDITIONING OF THE HEART: PROTECTIVE ROLE OF APELIN-13

If reperfusion follows an ischemia long enough to produce a myocardial infarction, a worsening of the damage takes place with increase of the infarct size, a more severe loss of contractility, the appearance of myocardial contracture and a greater incidence of arrhythmias. The overall injury is defined ischemia/reperfusion (I/R) injury. Reperfusion injury may be more severe than ischaemia injury and is characterised by impaired NO synthesis and increased ROS production. The heart may be protected against I/R injury by ischemic pre- (IPre) or post-conditioning (IPost). While the former is obtained with repeated 2 – 3 min coronary occlusions before the infarcting ischemia, the latter is performed with repeated 10 – 15 s occlusions starting a few seconds after the beginning of reperfusion. In protection a pivotal role is played by NO. The protection of the heart is also obtained with compounds which can mimic IPre or IPost. Apelin, an endogenous peptide, is produced in various tissues and organs. Out the different isoforms, apelin-13 is the most active one on cardiovascular system, where it displays positive inotropic effect and vasodilation. Apelin prevents I/R injury if given in the very early phase of reperfusion, but not before ischemia, i.e. it mimics IPost but not IPre. The activity of apelin is displayed via the G protein coupled receptor APJ. Apelin-induced protection includes infarct size limitation, a better recovery of contractility with reduction of contracture and prevention of arrhythmias. Apelin protects via RISK pathway elicited by PI3K-Akt system.