Toshiji Kanayama

Vasodilation produced by prostacyclin (PGI2) and 9(0)-thiaprostacyclin (PGI2-S) in the caninen femoral circulation

The action of 9(0)-thiaprostacyclin (PGI2-S) was compared with that of prostacyclin (PGI2) and papaverine in the femoral circulation of dogs. PGI2-S, injected into the dog femoral artery in a dose of 0.1 microgram or higher, produced marked vasodilation in the femoral artery without any change in blood pressure. The potentcy of PGI2-S was one tenth that of PGI2, and was a hundred times that of papaverine. The stability of PGI2-S in neutral solution was forty times that of PGI2.

Beneficial effects of a new prostacyclin analogue, KP-10614, on acute myocardial infarction in rats.

Summary: The potential therapeutic value of a new prostacyclin analogue, (4z, 16s)-4,5,18,18,19,19-hexadehydro-16,20-dimethyl-Δ6(9a)-9-(O)-methano-PGI1 (KP-10614), was studied in acute myocardial infarction in rats. Myocardial infarction was induced by ligation of the left coronary artery and ischemic injury was followed up to 4 h. The infarct size, evaluated by the area unstained by 2,3,5-triphenyltetrazolium chloride, reached 41.1 ± 1.4% of the left ventricle at 4 h. KP-10614 (3 ng/kg/min × 4 h) reduced the infarct size at 4 h significantly (26.5 ± 2.9%). At the same dose, KP-10614 inhibited ADP-induced ex vivo platelet aggregation significantly (21.5 ± 4.0% of the control aggregation), but did not alter the arterial blood pressure or heart rate. To assess the role of platelets in myocardial infarction, circulating platelets were reduced by about 95% with rabbit antiserum to rat platelets. In platelet-depleted rats, the infarct size decreased significantly to 24.1 ± 4.6% of the left ventricle at 4 h. These results suggest that platelets play an important role in expression of myocardial ischemic injury resulting from coronary artery occlusion in rats, and the ability of KP-10614 to decrease the infarct size appeared to be attributable, at least in part, to the inhibition of platelet aggregation or cellular metabolic effects produced by platelets at the site of tissue injury.