Cardioprotection: endogenous protective mechanisms promoted by prostacyclin

Abstract

Evidence is accumulating that acute stress situations such as ischemia, adrenergic dominance, and ouabain intoxication enhance production of endogenous substances (PgI2, adenosine, NO) which may protect the myocardium from harmful consequences of these stress situations. PgI2 and its stable analogue 7-oxo-PgI2 exert an early direct- and induce a delayed indirect antiischemic, antiarrhythmic, and cytoprotective effect. The direct action is shortlasting; it protects from myocardial ischemia and arrhythmias, at least partly, by its vasodilating, antiaggregatory, and "membrane-stabilizing" effects. The delayed, long-lasting PgI2-induced protection from postocclusion, reperfusion- and ouabain-arrhythmias is dose- (optimal 50 micrograms/kg) and time- (optimal 48 h after treatment) dependent. Its mechanism is probably based on a 7-oxo-PgI2 induced increase in the activity of Na/K-ATP-ase, and further, on a reduced sensitivity to beta-adrenergic agonists and to changes at the cardiac membrane level, resulting in a prolongation of the action potential duration and the effective refractory period.