Prostacyclin During Evolving Myocardial Infarction

Mueller, Hiltrud

Abstract

During the past decade evidence has developed that two prostaglandins importantly influence platelet activation and coronary vasomotor tone: Thromboxane A2 (TxA2) , a potent platelet aggregator and vasoconstrictor, and prostacyclin (PGI2), a powerful inhibitor of platelet aggregation, disperser of platelet aggregates and vasodilator. Results in the experimental animal and in man suggest that an increase in the transcardiac ratio of TxA2/PGI2 may initiate or enhance a vicious cycle for maintaining myocardial ischemia or even play a role in its pathogenesis. Data also suggest that increase in transcardiac TxA2 formation is related to the instability and intensity of ischemia and that exogenous PGI2 may dampen or abolish TxA2 induced abnormalities. We propose to evaluate the following questions: (1) Is transcardiac formation of TxA2 increased during evolving myocardial infarction (MI) in man? (2) Does exogenous PGI2 decrease transcardiac TxA2 liberation and platelet activation? and (3) Does PGI2 increase coronary perfusion of the ischemic myocardium, or does it cause a redistribution of flow away from the ischemic compartment? In 20 patients, catheters will be placed into the aorta and coronary sinus. Coronary sinus and great cardiac vein flow (thermodilution technique), aggregation of platelets, release of Beta-thromboglobulin and TxA2 by platelets in vivo and release of TxA2 from stimulated platelets in vitro will be measured. Studies will be performed at baseline, during 90 min of iv infusion of PGI2 and 45 min after its termination. A 24 hr PGI2 infusion will follow to evaluate the tolerance and effectiveness of PGI2, monitored by hemodynamic and platelet function studies. Subsequently, platelet function will be measured for 48 hrs to evaluate a possible platelet rebound phenomenon p- PGI2 infusion. 10 pts will be studied as control without PGI2 infusion. Preliminary results from sequential measurements of peripheral blood demonstrate that platelet function is greatly enhanced during evolving MI and that PGI2 decreases platelet activation. Very preliminary results of transcardiac studies suggest that release of TxA2 across the ischemic/infarcting compartment is enhanced. These studies also suggest that PGI2 does not appear to be a potent coronary vasodilator in the setting of acute MI. If PGI2 is effective in acute myocardial infarction we foresee its use in numerous forms of acute myocardial ischemia. PGI2 also could develop to an important intervention subsequent to intracoronary thrombolysis to reduce or abolish coronary reocclusion, prevent emboli from remaining thrombus at the coronary lesion and to abolish coronary vasospasm.