Histamine-induced spasm not significantly modulated by prostanoids in a swine model of coronary artery spasm.

The role of prostanoids in a swine model of coronary artery spasm was examined. Eighteen miniature pigs underwent endothelial denudation of the left coronary artery (left circumflex branch in 14 pigs and left anterior descending branch in 4 pigs) followed by high cholesterol feeding. Three months after the denudation, when coronary artery spasm was repeatedly provoked along the denuded portion of the coronary artery by histamine, the vasoconstrictive effect of thromboxane A2 and the preventive effects of indomethacin and prostacyclin against histamine-induced coronary artery spasm were examined. Intracoronary administration of thiothromboxane A2, 200 micrograms, a stable thromboxane A2 analog, failed to provoke coronary artery spasm (seven of seven cases) but nonselectively constricted the coronary artery by 33%. Intravenous administration of indomethacin, 2 mg/kg, or continuous intravenous infusion of prostacyclin, 50 ng/kg per min, failed to prevent histamine-induced coronary artery spasm (four of four and eight of eight cases, respectively), yet the spasm was all but prevented by intravenous pretreatment with diphenhydramine at a dose of 1 mg/kg. Thus, in this swine model, prostanoids may not play a primary role in the occurrence of coronary artery spasm.