Human Platelet Reactivity Research Articles

Albumin‐bound docosahexaenoic acid and collagen‐induced human platelet reactivity

An in vitro system designed to mimic the effect of various plasma nonesterified (polyunsaturated) fatty acids on platelet function and metabolism was employed. Human platelet aggregation induced by submaximal (1.8 micrograms/ml) collagen stimulation was significantly inhibited by 2 min preincubation with 20 microM albumin-bound docosahexaenoic acid (22:6n-3) (DHA), but not by the other fatty acids tested. [3H]Phosphatidic acid (PA) formation, an indicator of phospholipase C activation following platelet stimulation, was moderately inhibited by eicosapentaenoic acid (20:5n-3), 11,14,17-eicosatrienoic acid (20:3n-3), dihomo-gamma-linolenic acid (20:3n-6), as well as DHA, but not by arachidonic acid (20:4n-6); this inhibition of phospholipase C activation could not explain the differential effect of DHA on platelet aggregation. The decreased production of thromboxane A2 (TxA2), as assessed by [3H]12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) formation, may account for the inhibition of collagen-induced aggregation by 20 microM DHA. Surprisingly, preincubation with 40 microM albumin-bound DHA, even though resulting in greater inhibition of collagen-induced aggregation, had less impact on HHT formation. A small but significant increase in [3H]prostaglandin D2 (PGD2) levels following 3-min collagen stimulation may have contributed to the greater antiaggregatory effect of 40 muM DHA. It is concluded that increased plasma nonesterified DHA may contribute to the dampened platelet activation and altered metabolism following fish oil supplementation of the diet.

Interaction of ethanol, prostacyclin, and aspirin in determining human platelet reactivity in vitro.

Ethanol partitions into cellular membranes and alters membrane-associated phenomena in numerous cell types. Since platelet aggregation and its inhibition by prostacyclin are mediated by membrane-associated receptors and enzymes, we examined the interaction of ethanol, prostacyclin, and aspirin on human platelet reactivity. Using platelet-rich plasma, we examined the effect of increasing concentrations of ethanol (0.05% to 1.0%) on the platelet-inhibitory effects of a submaximal dose (5 x 10(-10) M) of prostacyclin, the concomitant production of cyclic 3',5'-adenosine monophosphate (AMP), and the release of thromboxane A2. Ethanol alone had little effect on platelet aggregation induced by 5 micrograms/ml collagen; however, it potentiated the inhibitory effect of prostacyclin on platelet aggregation in a dose-dependent manner in the range of 0.05% to 1.0% ethanol. Whereas prostacyclin increased platelet cyclic AMP levels, ethanol had no further effect on cyclic AMP levels. Ethanol alone reduced thromboxane A2 generation, but this effect could not totally account for the observed interaction of ethanol and prostacyclin on aggregation, since aspirin did not totally abolish the interaction. The dose range in which the ethanol/prostacyclin/aspirin interactions occur encompasses the plasma levels of ethanol that may be achieved by the consumption of alcoholic beverages. The results may, in part, explain the dose-related physiological and pathological consequences of chronic alcohol consumption on the cardiovascular system.

Human platelet reactivity with intact segments of rabbit aorta and selected regions of rabbit, rat and human aorta

A technique measuring platelet reactivity with vessel wall subendothelium has been modified to examine platelet reactivity with vessel pieces in place of intact segments of aorta of a specific diameter. This modification of Baumgartner's original technique(1) allows measurement of blood platelet reactivity with vessel pieces, 5x10 mm in size, mounted on perfusion chambers with “twist bands.” Adhesion and aggregation of human platelets to deendothelialized surfaces of intact segments of rabbit aorta and pieces of rabbit, rat and human aorta, were equivalent. This modification will expand the use of Baumgartner's technique to investigations of platelet vessel wall interactions using blood platelets and vessels from numerous experimental animal models and humans. It will also facilitate examination of possible differences in thrombogenocity of selected areas of vessels such as those exhibiting stages of atherosclerotic plaque formation.

Human platelet reactivity during stressful diagnostic procedures.

Conscious subjects undergoing cardiac catheterization and other diagnostic procedures showed a rise in platelet-aggregation response to adenosine diphosphate (ADP) one hour before and during the procedure. The responses returned towards normal one hour afterwards. The response to glass beads was decreased one hour before the procedure, but was unchanged in subsequent samples. Plasma-free fatty acid (FFA) levels were increased during the procedure, and one hour afterwards, but had returned to normal by the following day. Platelet counts were slightly reduced on the day after the procedure. It is suggested that catecholamines released due to emotional stress may be responsible for the increased platelet responses to ADP and that this could influence the development of thrombosis and atherosclerosis.