Prostanoids, Coronary Circulation and Coronary Artery Spasm in Open Chest Dogs and Miniature Pigs

Effects of prostanoids on coronary circulation were studied in anesthetized open chest dogs with intact coronary arteries or in closed chest Gottingen miniature pigs with denuded vessels. In the latter model, coronary artery spasm was repeatedly provoked at the previously denuded area by histamine i.c. after pretreatment with cimetidine i.v. H₂-blocker. In the canine model, prostacyclin (PGI₂) dilated to a greater extent the diameter of the large epicardial coronary artery than did PGE₂, and both equally reduced the total coronary resistance. Vasoconstrictive effects of carbocyclic thromboxane A₂, a stable analogue of thromboxane A2 (TxA₂) on the epicardial coronary artery was augmented from 1.1±0.3 to 6.5±1.3% (p<0.01) after pretreatment with cyclooxygenase inhibitors. In case of Göttingen miniature pigs 3 months after endothelial denudation and cholesterol freeding, neither PGI₂ nor indomethacin prevented histamine-induced coronary artery spasm. Thiothromboxane A₂, a stable analogue of TxA₂, did not provoke coronary artery spasm in the animals. Therefore, prostanoids may not be crucial to the provocation or prevention of coronary artery spasm from which myocardial ischemia ensues.