Prevention of blockage of partially obstructed coronary arteries with prostacyclin correlates with inhibition of platelet aggregation.
Coronary arteries (circumflex or left anterior descending) of anesthetized dogs were partially obstructed to approximately 5% of the normal lumen size by fitting a plastic cylinder around the vessel. Under these conditions, blood flow in the artery was not maintained but, instead, gradually declined over a few minutes until the vessel was completely blocked. Shaking the plastic obstructor restored blood flow temporarily, however, flow gradually declined again to zero. Sometimes flow was spontaneously restored by immediate increases that occurred at irregular intervals while, on other occasions, blood flow had to be restored by shaking the obstructor every time the rate declined to near zero. Intravenous infusion of prostacyclin (PGI2) at 15 to 150 ng/kg/min reversed and prevented the blockage of the coronary arteries. The efficacy of PGI2 in preventing blockage correlated with inhibition of ADP-induced platelet aggregation in platelet rich plasma prepared from blood samples withdrawn from the dogs during PGI2 infusion. Other coronary vasodilators, nitroglycerin and PGE2, that have no antiaggregatory effects, failed to prevent blockage whereas PGE1 and indomethacin, which do block aggregation, also prevented blockage of the vessels. PGI2 or its precursor, PGH2, dripped topically on the obstructed site prevented the blockage of the artery. This local effect of IGI2 could be obtained with amounts too small to cause systemic inhibition of platelet aggregation. The results show that PGI2 prevents blockage of partially obstructed coronary arteries and this effect correlates with inhibition of platelet aggregation. Furthermore, the data suggest that locally produced PGI2 may have a local antiaggregatory effect without inhibiting platelet aggregation in the general circulation.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000287:Administration, Topical; D000818:Animals; D001158:Arteries; D003327:Coronary Disease / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D004285:Dogs; D011464:Epoprostenol / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007263:Infusions, Parenteral; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000627:therapeutic use*; D011463:Prostaglandins H / Q000008:administration & dosage / Q000627:therapeutic use
D011453:Prostaglandins; D011463:Prostaglandins H; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D005996:Nitroglycerin; D007213:Indomethacin