The effect of acetylsalicylic acid and indomethacin on rabbit platelet adherence to collagen and the subendothelium in the presence of a low or high hematocrit

We have examined the effect of ASA and indomethacin on rabbit platelet adherence to collagen or the subendothelium over a range of hematocrits. Platelet adherence to the surfaces was measured in vitro using a rotating probe. Washed rabbit platelets were prelabeled with 51Cr and resuspended in media containing 4% albumin, apyrase and physiological concentrations of calcium and magnesium. ASA, indomethacin or their solvents were incubated for 10 min with the platelet suspensions before washed rabbit red blood cells were added. Collagen-coated glass cylinders or everted segments of de-endothelialized rabbit thoracic aorta were mounted on probes and rotated for 10 min at 200 rpm at 37°C in a suspension of washed platelets containing various concentrations of red blood cells. The surfaces were rinsed in EDTA to remove platelet aggregates and the radioactivity associated with the surfaces was measured. Under the conditions of flow used in this system the hematocrit determined whether or not an inhibitory effect of ASA on the adherence of rabbit platelets was demonstrable. ASA inhibited platelet adherence to collagen and to the subendothelium at a low hematocrit, but at a 40% hematocrit it did not. In contrast, indomethacin showed an inhibitory effect on platelet adherence to the surfaces even at a 40% hematocrit. ASA and indomethacin were tested at concentrations that were higher than those required to block the arachidonate pathway, as measured by malondialdehyde formation. Under these conditions, ASA did not inhibit platelet adherence, indicating that the arachidonate pathway does not play a major role in platelet adherence at a 40% hematocrit. Indomethacin inhibited adherence by a mechanism that was probably independent of the inhibition of the platelet cyclo-oxygenase. These results show that the magnitude of the physical force imposed on the platelets by the red cells determines the extent of platelet adherence and modifies the effects of drugs on adherence to the surfaces.