vapiprost and Myocardial-Infarction

To compare a thromboxane antagonist (GR3219) with aspirin in patients with prolonged chest pain and ST segment depression to see if the frequency of attacks of chest pain was reduced.. The trial was part of a study comparing GR3219 with aspirin, and streptokinase with placebo and comprised the GR3219/aspirin leg. Thirty one patients were randomly assigned to GR3219 80 mg twice daily and 28 to aspirin 300 mg daily. The patients were under the age of 76 and admitted to a coronary care unit within 6 hours of continuous chest pain. The ECG showed at least 1 mm of flat or down-going ST segment. The patients kept diaries of their pain over the subsequent 31 days.. Seventy percent of patients developed further chest pain. There was no difference between the pattern of recurrent chest pain according to which drug was used.. The hypothesis that specific thromboxane A blockade with GR3219 would be more efficacious than aspirin was not supported by these results.

Topics: Aged; Aspirin; Biphenyl Compounds; Coronary Care Units; Double-Blind Method; Electrocardiography; Female; Heptanoic Acids; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Recurrence; Streptokinase; Thromboxane A2

The photochemical reaction between rose bengal and light (540 nm) produces thrombotic occlusion in rat coronary artery. We have now developed an experimental myocardial infarction (MI) model by photochemically induced thrombosis (PIT) in rats and investigated the mechanisms responsible for the induction of MI. PIT in the coronary artery induced myocardial ischemia, which was determined by tissue oxygen tension (tpO2), and resulted in MI. Pretreatment with a thromboxane (TX) A2-receptor antagonist, vapiprost, prevented a decrease in myocardial tpO2 and markedly reduced the MI area, although vapiprost inhibited collagen-induced platelet aggregation by 30% ex vivo. An ADP-induced platelet aggregation inhibitor, clopidogrel, also reduced the MI area. In contrast to vapiprost, clopidogrel inhibited collagen-induced platelet aggregation by 90% ex vivo. Pretreatment with a 5-HT2-receptor antagonist, ketanserin, which did not inhibit collagen-induced platelet aggregation ex vivo, prevented the decrease in myocardial tpO2 and reduced the MI area. These results suggest that TXA2, 5-HT and ADP play a role in the induction of MI and that platelet aggregation and other factors induce ischemia in this model.

Topics: Animals; Biphenyl Compounds; Clopidogrel; Coronary Vessels; Disease Models, Animal; Electrocardiography; Heptanoic Acids; Ketanserin; Male; Myocardial Infarction; Oxygen; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Thrombosis; Ticlopidine