Susumu Mizogami

The bile acid binding and hypocholesterolemic activity of anion—exchange resins bearing the imidazolium salt group

Abstract A new anion—exchange resin bearing imidazolium pendant groups on a polystyrene copolymer skeleton was synthesized. This resin is a white odorless powder and the bile acid binding activities in vitro were much more potent than those of cholestyramine. The ion- exchange equilibrium coefficient K phosphoric acid ion − bile acid ion − was 271, compared to that of cholestyramine which was 32. The hypocholesterolemic activity of this resin in cholesterol-fed rabbits proved to be 1.5-fold more potent than that of cholestyramine. Thus, the effective reduction of plasma cholesterol may be achieved with significantly lower doses of this resin.

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.