Prevention of coronary platelet aggregation with a phosphodiesterase inhibitor RX-RA 69.
The formation and prevention of coronary platelet thrombi (CPT) was studied in a modified Folts model in 23 anaesthetized dogs. The left circumflex coronary artery was acutely damaged and narrowed until resting flow started to fall. Spontaneous sharp decrease of flow indicated the acute formation of CPT. Intravenous infusion of 30 ng/kg/min of PGI2 prevented the formation of CTP. The effect lasted 3-7 min after termination of the infusion. RX-RA 69 a potent inhibitor of platelet phosphodiesterase (IC50 of 1 X 10(-9) mol/1) inhibited the formation of CPT for 9 and 18 min when 60 and 120 micrograms/kg were administered i.v. The results demonstrate that platelet aggregation induced by acute damage of the vascular wall can be inhibited by a potent PDE inhibitor.
Machleidt
C
C
Rose
P
P
Mittmann
U
U
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology*
D011743:Pyrimidines; C035537:RX-RA 69; D011464:Epoprostenol; D015105:3',5'-Cyclic-AMP Phosphodiesterases