Cazenave Jp

The Influence of Red Blood Cells on the Effects of Aspirin or Sulphinpyrazone on Platelet Adherence to Damaged Rabbit Aorta

Summary. The effects of acetylsalicylic acid (ASA; aspirin) or sulphinpyrazone (SP) on the adherence of washed rabbit platelets to the subendothelial surface of an everted aorta mounted on a probe or to the subendothelial surface of a rabbit aorta attached to a perfusion apparatus were examined. ASA had no effect on platelet adherence to a damaged aorta perfused with a suspension of washed platelets in a medium containing 10% red blood cells (RBC); SP was slightly inhibitory at high concentration. When damaged rabbit aortae were everted on a probe and rotated in a suspension of washed platelets to which RBC were added to a packed cell volume of 10%, both ASA and SP inhibited platelet adherence to the damaged vessel wall. When the PCV was 40%, ASA was not inhibitory and SP reduced platelet adherence only at very high concentrations. It is therefore unlikely that, at the concentrations achieved in man, SP exerts an effect on platelet adherence. The different effects of ASA and SP on platelet survival do not appear attributable to their effects on platelet adherence.

The effect of a platelet-derived growth factor on the proliferation of rabbit arterial smooth muscle cells in tissue culture

Abstract Thrombin and collagen induced the release of a growth factor from washed rabbit platelets which requires a serum factor derived from platelet poor plasma for maximum proliferation of the smooth muscle cells. The release of the platelet-derived growth factor by thrombin and collagen parallels the release of serotonin from these platelets. Therefore it is possible to use rabbit smooth muscle cells and rabbit platelets and 3H-thymidine to examine the effect of factors governing the release of the platelet-derived growth factor and the factors governing its effect on smooth muscle cell proliferation. These results show that it is possible to examine the effect of collagen, which is the principal stimulus to platelet release in the vessel wall, in an in vitro system to rapidly study its effect on the release of the platelet-derived growth factor.

EFFECT OF HEPARIN AND THROMBIN ON PLATELET ADHERENCE TO THE SURFACE OF RABBIT AORTA

Abstract Platelet adherence to both the damaged and undamaged surfaces of rabbit aorta in perfusion experiments in vitro was inhibited by heparin. The preparation of the vessel segments for these perfusion studies required 30 to 60 minutes because of the need to tie off all of the small vessels. In other experiments in which damaged or undamaged vessel segments were everted on a probe, the preparation of the vessels could be done more quickly and heparin did not inhibit platelet adherence. However, exposure of either the damaged or undamaged surfaces used in the latter type of experiment to thrombin markedly promoted platelet adherence to the surfaces. Heparin inhibited this effect. It seems likely that during the preparation of the aortas for the perfusion studies, thrombin generation occurred in the vessels. Thus, in preparing aortic segments for studies of platelet adherence, thrombin generation must be avoided. Since thrombin enhanced platelet adherence to undamaged endothelial surfaces, it may be that thrombin formation in vivo could cause platelet adherence to vessel walls from which endothelial cells have not been lost.

Effect of indomethacin, sulfinpyrazone and dipyridamole on the release of the platelet-derived growth factor.

Abstract Inhibition of the platelet release reaction inhibits the release of the platelet-derived growth factor (PDGF) in response to collagen. However, neither indomethacin nor sulfinpyrazone were effective inhibitors of the release of PDGF when high concentrations of collagen or thrombin were used. Since these drugs did inhibit the cyclo-oxygenase release pathway, it appears that the products derived from the metabolism of arachidonic acid are not important in the smooth muscle cell response to PDGF. We could not show any effect of the inhibitors of the cyclo-oxygenase pathway on the response of the smooth muscle cell to PDGF. Dipyridamole was found to inhibit the incorporation of 3H-thymidine in smooth muscle cells stimulated with PDGF. This effect, however, was not due to inhibition of smooth muscle cell proliferation but to the diminished uptake of 3H-thymidine by the smooth muscle cells. The results of the experiments indicate that indomethacin, sulfinpyrazone and dipyridamole are not effective inhibitors of the platelet release of PDGF.