Role of Platelet-Prostaglandin Synthesis in Shear-Induced Platelet Alterations

Abstract

Exposure of citrated human platelet-rich plasma (C-PRP) to mechanical shear stress has been shown to induce platelet aggregation (PAG), release from platelets of dense granule contents, and platelet lysis. The mechanisms involved in these shear-induced platelet alterations have not been defined. To examine the possible role of prostaglandin (PG) synthesis in shear-induced platelet reactions, C-PRP was sheared in a concentric cylinder viscometer for 5 min at stresses ranging from 50 to 460 dyn/sq cm in the presence or absence of acetylsalicylic acid (ASA), a potent inhibitor of platelet thromboxane-A2 synthesis. With increasing shear stress, a progressive loss of platelets from the sheared C-PRP was observed due to PAG and adherence of the aggregates to the viscometer surfaces. PAG was associated with a progressive release from platelets of serotonin and β-thromboglobulin (β-TG) and formation of malondialdehyde (MDA) a stable end-product of platelet cyclooxygenase-mediated arachidonate metabolism reflecting thromboxane-A2 synthesis. At stresses above 150 dyn/sq cm, a progressive loss of lactic dehydrogenase (LDH) was observed, indicating platelet damage. ASA (0.1 mM) completely abolished shear-induced MDA formation and caused a 50% reduction of shear-induced release of serotonin and β-TG. However, ASA did not cause an appreciable reduction of shear-induced PAG and did not alter the extent of or threshold for shear-induced platelet lysis. The findings indicate that (1) shear-induced release from platelets of dense and α-granule contents is associated with and potentiated by stimulation of thromboxane-A2 synthesis and (2) thromboxane-A2 synthesis appears to play no appreciable role in shear-induced PAG or platelet lysis in this system.