[(5Z,13E,9 alpha,11 alpha,15S)-2,3,4-Trinor - 1,5 - inter-m - phenylene - 6,9 - epoxy - 11,5 - dihydroxy - 15 - cyclohexyl - 16,17,18,19,20-pentanor]- prosta-5,13-dienoic
acid (
sodium salt) (
CG 4203) is a new stable
epoprostenol (
prostacyclin) analogue with a relative platelet antiaggregatory potency of 0.46 (
ADP aggregation in vitro) and a hypotensive potency of 0.14 (anaesthetized rat i.v.) as compared to
epoprostenol. In isolated perfused rat hearts,
CG 4203 (4.64 X 10(-9) mol/l) significantly attenuated arrhythmias and loss of left ventricular
creatine kinase (CK) activity observed in control hearts after 30 min perfusion with hypoxic and 30 min reperfusion with oxygenated
Krebs-Ringer solution. In anaesthetized rats,
CG 4203 (1.0 microgram X kg-1 X min-1 i.v.) significantly reduced incidence of
ventricular fibrillation and increase in plasma CK activity after
ligation of the left coronary artery. Infusion of 1.0 and 2.15 micrograms X kg-1 X min-1
CG 4203 i.v. in anaesthetized rats dose-dependently inhibited electrocardiographic changes, i.e. ST depression observed after i.v. injection of 1.0 IU X kg-1
vasopressin. In rat models of sustained myocardial
hypoxia,
myocardial infarction, and transient cardiac
ischemia,
CG 4203 thus exerts cardioprotective effects which, depending on the model considered, may be ascribed to either its vasodilatory, coronary dilatory, antiaggregatory or
epoprostenol-like cytoprotective activity.