LOW REGULATORY VOLUME DECREASE RATE IN PLATELETS FROM ISCHEMIC PATIENTS - A POSSIBLE ROLE FOR HEPOXILIN A(3) IN THROMBOGENICITY

Hepoxilin-A(3) (Hx-A(3)) is produced by platelets in response to shear -stress. It has an antithrombotic effect on platelets, A low Hx-A(3) l evel may contribute to the high thrombogenic state that exists in pati ents with acute coronary syndromes. Since we have previously demonstra ted that the regulatory volume decrease (RVD) of human platelets expos ed to hypotonic solutions is controlled by Hx-A(3), it is possible tha t the RVD rate reflects Hx-A(3) activity. In this study, the RVD rate of platelets taken from a healthy control group (n = 21) was compared to that of patients with chronic ischemic heart disease (n = 23), acut e ischemic heart disease (n = 24) and acute myocardial infarction (MI, n = 29). The RVD rate of the control group was significantly higher t han the other three groups (P < 0.001). The addition of 100 nM of Hx-A (3) to the platelets of eight patients with MI increased their RVD rat e to that of the controls. Patients with diabetes mellitus or hyperten sion have the lowest RVD rates, Medications such as aspirin, heparin, and streptokinase did not affect the Hx-A(3) activity of platelets obt ained from patients with ischemic heart disease. The results of the pr esent study indicate that patients with acute ischemia may have a low level of platelet Hx-A(3) activity. This possible low level of Hx-A(3) activity may be associated with a failure to develop an antithromboti c reaction to the shear-stress forces generated during acute ischemia.