THE ROLE OF EXTRAPLATELET THROMBOXANE-A2 IN UNSTABLE ANGINA INVESTIGATED WITH A DUAL THROMBOXANE-A2 INHIBITOR - IMPORTANCE OF ACTIVATED MONOCYTES

Background: The role of thromboxane A2 (TxA2) in unstable angina has n ot yet been defined. TxA2 receptor antagonists may be of value in stud ying this role. Methods: To investigate whether TxA2 has a pathogeneti c effect on the occurrence of myocardial ischemia and from what source TxA2 originates, we studied TxA2 formation by unstimulated monocytes from patients with unstable angina (n=40), stable effort angina (n=20) , and controls (n=20). We also compared the effects of picotamide (120 0 mg/day), a TxA2-synthase inhibitor and TxA2-receptor antagonist, wit h those of aspirin (325 mg/day) on myocardial ischemia and TxA2 format ion by monocytes and platelets. The double-blind randomized study was performed on patients with unstable angina on continuous Holter monito ring. Results: In the presence of autologous lymphocytes, unstimulated monocytes from patients with unstable angina formed significantly (P< 0.001) more TxA2 than those from controls or from patients with effort angina. Although TxA2 formation by circulating monocytes and platelet s was inhibited to a greater degree by aspirin than by picotamide (88/-6 and 98+/-2%, respectively, versus 65+/-2 and 74+/-1%, P<0.001), as pirin failed to affect the occurrence of myocardial ischemia whereas p icotamide significantly (P<0.001) reduced the number of anginal attack s (84.8%), silent ischemic episodes (64.2%), and overall duration of i schemia (69.8%), in comparison to the run-in period. Conclusions: Thes e results indicate that TxA2 formed by monocytes contributes to the pa thogenesis of myocardial ischemia in unstable angina. TxA2 formation o ccurs mainly in extravascular spaces, probably within the coronary vas cular wall. Picotamide appears to control myocardial ischemia effectiv ely in patients with unstable angina.