Original Article: Low Regulatory Volume Decrease Rate in Platelets from Ischemic Patients: A Possible Role for Hepoxilin A₃ in Thrombogenicity

Abstract

Hepoxilin-A₃ (Hx-A₃) is produced by platelets in response to shear-stress. It has an antithrombotic effect on platelets. A low Hx-A₃ level may contribute to the high thrombogenic state that exists in patients with acute coronary syndromes. Since we have previously demonstrated that the regulatory volume decrease (RVD) of human platelets exposed to hypotonic solutions is controlled by Hx-A₃ it is possible that the RVD rate reflects Hx-A₃ 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), acute ischemic heart disease (n = 24) and acute myocardial infarction (MI, n = 29). The RVD rate of the control group was significantly higher than the other three groups (P < 0.001). The addition of 100 nM of Hx-A, to the platelets of eight patients with MI increased their RVD rate to that of the controls. Patients with diabetes mellitus or hypertension have the lowest RVD rates. Medications such as aspirin, heparin, and streptokinase did not affect the Hx-A₃ activity of platelets obtained from patients with ischemic heart disease. The results of the present study indicate that patients with acute ischemia may have a low level of platelet Hx-A₃ activity. This possible low level of Hx-A, activity may be associated with a failure to develop an antithrombotic reaction to the shear-stress forces generated during acute ischemia.