On the nature and molecular basis of prostacyclin induced late cardiac changes.

The late appearing and long-lasting cardiac effects induced by PgI2 or its stable analogue 7-oxo-PgI2 described by us first in 1983 include: 1.) antiischemic, 2.) antiarrhythmic, 3.) selective electrophysiological and 4.) cardiac cytoprotective changes. Evidence for 1.: Protection from myocardial ischemia due to coronary occlusion in dogs furthermore a significant diminution of ischemic loss of the myocardial ATP and CP content and of the myocardial lactate accumulation in excised rat heart exposed to global ischemia. 2: Protection from postocclusion and reperfusion arrhythmias in dogs. 3: A selective prolongation of the ventricular refractory period (VERP) as well as of the action potential duration (APD90) in the isolated rabbit papillary muscle furthermore prolongation of QT distance and VERP in the rabbit and the guinea pig heart "in situ". 4.: The cardiac cytoprotective effect, i.e. ischemic loss of intracellular K+ and ischemic gain of intracellular Na+ in isolated hearts of 7-oxo-PgI2 treated guinea pigs subjected to 25 min global ischemia was significantly moderated. These protective actions proved to be dose and time dependent - maximal effects appeared 48 hrs after administration of a single dose of 50 micrograms/kg i.m. 7-oxo-PgI2. These effects are certainly not due to 7-oxo-PgI2 itself but this latter seems to be indispensable for induction of a long acting principle, which can probably be extracted from hearts of pretreated animals and this substance of lipoid character exerts electrophysiological effects similar to those observed after 7-oxo-PgI2 pretreatment. Pretreatment may also reduce isoproterenol induced heart rate increase and prolong bleeding time in conscious rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)