THE NEWLY SYNTHESIZED COMPOUND E-5510 IS A HIGHLY POTENT ANTIPLATELET AGENT

1987 ◽  
Author(s):  
K Harada ◽  
T Fujimori ◽  
M Kogushi ◽  
M Kogushi ◽  
I Yamatsu ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Human Subjects ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
Inhibitory Effect ◽  
Experimental Animals ◽  
Antiplatelet Effect

Our newly synthesized compound, 4-cyano-5,5-bis(methoxy-phenyl)-4-pentenoic acid (E-5510) has highly potent antiplatelet activity. In this paper, the effects of E-5510 on platelet functions in vitro and ex vivo in human and in various experimental animals are examined.E-5510 inhibited human platelet aggregation induced by collagen, arachidonate, ADP, PAF and epinephrine (IC50: 1.5, 0.7, 2.0, 1.6 and 1.1 uM, respectively). Thrombin-induced platelet aggregation, which was not inhibited by aspirin and U-53059 (lC50s: 100 uM), was also inhibited by this compound (IC50: 21uM). The IC50 of E-5510 in thrombin-induced ATP secretion fromhuman platelets was only 2 uM. Platelet adhesion to a collagen coated disk, whichwas measured by the method of Buchanan et al (Prost. Leuko. Med., 21, 157, 1986) was inhibited by E-5510 (IC50: 19.3 uM) butnot by aspirin and U-53059. In the PRP ofthe guinea pig, the beagle and the monkey, E-5510 inhibited collagen-induced platelet aggregation in vitro to the same degree as in human PRP(IC50: 1.2, 0.6 and 1.5 uM, respectively). After being administered orally to guinea pigs, E-5510 exhibited extremely potent ex vivo inhibitory effect in collagen-induced platelet aggregation with a very low ED50 of 0.05 mg/kg. In contrast, the ED50’s of ticlopidine, aspirin and U-53059 were 300 , 27.2 and 1.0 mg/kg, respectively. In beagles and monkeys E-5510 also showed ex vivo antiplatelet effects at 0.01 and 0.003 mg/kg, respectively. This effect continued for more than 8 hrs. and disappeared within 24 hrs. The antiplatelet effect in human PRP was highly correlated with that in PRP of experimental animals in which the ex vivo effects were confirmed at a very low dose. Thus, E-5510 will ensure to exert the antiplatelet effect after oral administration to human subjects.In summary, E-5510 is unique among the known antiplatelet agents since it has potent inhibitory effects on thrombin-induced platelet activation and platelet adhesion to collagen. It was also shown that this compound had an ex vivo antiplatelet effect at an extremely low ED50. Our results suggest that E-5510 will be a beneficial agent for antiplatelet therapy in humans.

The d-Enantiomer Form of Indobufen Totally Accounts for the Anti-Cyclooxygenase and Antiplatelet Activity Ex Vivo and for the Increase in Bleeding Time by Indobufen in Man

1992 ◽  
Vol 67 (02) ◽  
pp. 258-263 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
An Yan ◽  
Walter Bernini ◽  
Daniela Giannessi ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Plasma Levels ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Random Sequence ◽  
Antiplatelet Agent ◽  
Antiplatelet Drug ◽  
Double Blind

SummaryIndobufen is an antiplatelet drug able to inhibit thromboxane production and cyclooxygenase-dependent platelet aggregation by a reversible inhibition of cyclooxygenase. Indobufen exists in two enantiomeric forms, of which only d-indobufen is active in vitro in inhibiting cyclooxygenase. In order to verify that also inhibition of platelet function is totally accounted for by d-indobufen, ten patients with proven coronary artery disease (8 male, 2 female, age, mean ± S.D., 58.7 ± 7.5 years) were given, in random sequence, both 100 mg d-indobufen and 200 mg dl-indobufen as single administrations in a double-blind crossover design study with a washout period between treatments of 72 h. In all patients thromboxane (TX) B2 generation after spontaneous clotting (at 0, 1, 2, 4, 6, 8, 12, 24 h), drug plasma levels (at the same times), platelet aggregation in response to ADP, adrenaline, arachidonic acid, collagen, PAF, and bleeding time (at 0, 2, 12 h) were evaluated after each treatment. Both treatments determined peak inhibition of TXB2 production at 2 h from administration, with no statistical difference between the two treatments (97 ±3% for both treatments). At 12 h inhibition was 87 ± 6% for d-indobufen and 88 ± 6% for dl-indobufen (p = NS). Inhibition of TXB2 production correlated significantly with plasma levels of the drugs. Maximum inhibitory effect on aggregation was seen in response to collagen 1.5 pg/ml (63 ± 44% for d-indobufen and 81 ± 22% for dl-indobufen) and arachidonic acid 0.5-2 mM (78 ± 34% for d-indobufen and 88 ± 24% for dl-indobufen) at 2 h after each administration. An effect of both treatments on platelet aggregation after 12 h was present only for adrenaline 2 μM (55 ± 41% for d-indobufen and 37 ± 54% for dl-indobufen), collagen 1.5 pg/ml (69 ± 30% for d-indobufen and 51 ± 61% for dl-indobufen), arachidonic acid 0.5-2 mM (56 ± 48% for d-indobufen and 35 ± 49% for dl-indobufen). The extent of inhibition of TX production and the extent of residual platelet aggregation were never significantly different between treatments. Bleeding time prolongation was similar in the two treatment groups without showing a pronounced and long lasting effect (from 7.0 ± 2.0 min to 10.0 ± 3.0 min at 2 h and 8.0 ± 2.0 min at 12 h for d-indobufen; from 6.0 ±1.0 min to 8.5 ± 2.0 min at 2 h and 8.0 ± 1.0 min at 12 h for dl-indobufen). These results demonstrate that the biological activity of dl-indobufen as an antiplatelet agent in vivo is totally accounted for by d-indobufen.

Effect of Sulphinpyrazone (SP) Aspirin (ASA) and Dipyridamole (DP) on Plateletvessel Wall Interaction after Oral Administration to Rabbits

1979 ◽  
Author(s):  
J.A. Davies ◽  
V.C. Menys
Keyword(s):  
Clinical Trials ◽  
Platelet Aggregation ◽  
Vessel Wall ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Human Dose ◽  
Wall Interaction ◽  
Adhesion Of Platelets

Clinical trials of anti-platelet drugs have suggested that they may be useful in the prevention of thrombotic disease. While such drugs inhibit platelet function, those which act on cyclooxygenase also reduce PGI2 synthesis and may interfere with tne natural antithrombotic properties of the vessel wall. We studied the effects of SP, ASA and OP ex vivo on the platelet-vessel wall interaction. Rabbits were dosed by mouth with drug (at about twice the weight-adjusted human dose) or placebo for 5 days, then exsanguinated and aortas removed. Washed platelets prepared from the blood were labelled with 51Cr. and their adhesion to everted aortapr epared from treated or control rabbits was measured in a perfusion device. PGI2-like activity in aortic rings was assayed by its inhibitory effect on platelet aggregation to ADP. Adhesion of platelets to aort as from SP- treated rabbits was i ncreased (p < 0.025), PGI2 - like activity was partially inhibited, but over all adhesion of SP-treated platelets to aor tas f rom SP-treated animals reduced by 30% (p < 0.02). Adhesion to aortas of ASA- treated rabbits was sliahtly inc r ea=-.ed (p > 0 . 1) , PGI 2 - l ike act ivi ty abolished , and no overall reduc tion in platelet adhesion seen. DP had no effecton adhesion or PGI-like activity. These results support the evidence that cyclo-oxygenase inhibitors reduce the inherent resistance of the vessel wall to platelet adhesion. However with SP, inhibitory effects on platelets appear to be more important.

Novel 12-LOX Inhibitor ML355 Attenuates Platelet Reactivity and Impairs Thrombus Growth, Stability and Vessel Occlusion In Vivo

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3442-3442 ◽  
Author(s):  
Reheman Adili ◽  
Theodore R Holman ◽  
Michael Holinstat
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Vessel Occlusion ◽  
Growth Stability

Abstract Background: Adequate platelet reactivity is required for platelet adhesion and aggregation at the site of vascular injury to maintain hemostasis. However, excessive platelet reactivity can also lead to the formation of occlusive thrombi, the predominate underlying cause of myocardial infarction and stroke. While current anti-platelet treatments limit platelet function, they often result in an increased risk of bleeding. 12-lipoxygenase (12-LOX), an oxygenase highly expressed in the platelet, has been demonstrated by our lab and others to regulate PAR4 and GPVI-mediated platelet reactivity suggesting a role of 12-LOX in regulation of vivo thrombosis. However, the ability to pharmacologically target 12-LOX in vivo has not been established to date. Aims: To determine how 12-LOX regulates thrombus formation in vivo and whether platelet 12-LOX is an effective target for anti-platelet therapeutics, wild-type (WT) or 12-LOX deficient (12-LOX-/-) mice were treated with or without the 12-LOX inhibitor, ML355, and were assessed for inhibitory effects on platelet activation in vitro, ex-vivo and in vivo. Methods: The effect of the novel 12-LOX inhibitor ML355 on human platelet function was assessed in vitro by platelet aggregometry, ex vivo by perfusion chamber. In vivo thrombus formation and vessel occlusion in small and large vessels were studied in 12-LOX-/-, WT mice and mice treated with ML355 using intravital microscopy using the FeCl3 injury models. Results: Using in vitro platelet aggregation assays, ML355 dose dependently inhibited thrombin, PAR1-AP, and PAR4-AP-induced aggregation in washed human platelets. Interestingly, the negative regulatory effects of ML355 inhibition of 12-LOX can be overcome by high concentration of thrombin. Additionally, ML355 was able to attenuate ADP-induced platelet aggregation both in platelet-rich-plasma and whole blood. In ex vivo flow chamber assays, platelet adhesion and thrombus formation on collagen-coated surfaces at high shear was attenuated in both mouse and human whole blood after incubation with ML355. Further, platelet aggregation and thrombus growth in 12-LOX-/- mice was impaired in FeCl3-induced mesenteric or carotid artery thrombosis models. Thrombi in 12-LOX-/- mice were unstable and frequently form emboli, which resulted in impaired vessel occlusion or reopening. Additionally, thrombus formation and vessel occlusion was impaired in ML355 treated WT mice. Conclusions: The highly selective 12-LOX inhibitor ML355 inhibits platelets aggregation induced by various platelet agonists and ML355 inhibition of platelet function is not agonist specific. Platelet function at high shear in ex vivo conditions in both mice and human was attenuated in the presence of ML355. Thrombus growth, stability, and vessel occlusion was impaired in mice deficient for 12-LOX. Finally, the highly selective 12-LOX inhibitor ML355 attenuates thrombus formation and prevents vessel occlusion in vivo. Our data strongly indicates 12- LOX is an important determinant of platelet reactivity and inhibition of platelet 12-LOX may represent a new target for anti-platelet therapeutics. Disclosures No relevant conflicts of interest to declare.

Effects of Magnesium on Platelet Aggregation and Adhesion

1994 ◽  
Vol 72 (06) ◽  
pp. 912-918 ◽  
Author(s):  
M Gawaz ◽  
I Ott ◽  
A J Reininger ◽  
F-J Neumann
Keyword(s):  
Myocardial Infarction ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Adhesion ◽  
Bleeding Time ◽  
Magnesium Deficiency ◽  
Ex Vivo ◽  
Surface Expression ◽  
Activated Platelets

SummaryMagnesium deficiency and its association with platelet hyperreactivity has been well recognised in a variety of diseases including myocardial infarction, preeclampsia, and diabetes. In order to investigate potential effects of intravenous Mg2+ supplementation, platelet function was studied by measurements of in vitro bleeding time (BT) and of fibrinogen (Fg)-mediated aggregation of washed platelets. In addition, the effect of Mg2+ on platelet adhesion onto immobilised Fg, on Fg binding to activated platelets, and on surface expression of GMP-140 or GP53 was evaluated. Mg2+(4 mM) prolonged in vitro BT by 30% and inhibited Fg-mediated aggregation significantly, independent of the agonist used to initiate platelet aggregation (ADP, collagen, epinephrine, thrombin, phorbol ester). Adhesion of resting platelets to immobilised Fg was reduced by 50% in the presence of 2 mM Mg2+. Moreover, Mg2+ reduced Fg binding to ADP- or collagen-stimulated platelets as well as surface expression of GMP-140 with an IC50 of approximately 3 mM. Intravenous administration of Mg2+ to healthy volunteers inhibited both ADP-induced platelet aggregation (p <0.05) by 40% and binding of Fg or surface expression of GMP-140 by 30% (p <0.05). Thus, pharmacological concentrations of Mg2+ effectively inhibit platelet function in vitro and ex vivo.

Studies on the Effect of Platelet Inhibitors on Platelet Adhesion to Collagen and Collagen-Induced Human Platelet Activation

1985 ◽  
Vol 53 (03) ◽  
pp. 337-342 ◽  
Author(s):  
S Krishnamurthi ◽  
V V Kakkar
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Platelet Adhesion ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Antiplatelet Agents ◽  
Calmodulin Antagonist ◽  
Release Reaction ◽  
Low Concentrations

SummaryThe effect of pyridoxal 5’-phosphate (PALP) and trifluoperazine (TFPZ), the calmodulin antagonist, on in vitro platelet adhesion to collagen and collagen-induced platelet activation was studied using platelet-rich-plasma (PRP) or washed platelets (WPL). Platelet aggregation and [14C]-5HT release induced by “threshold” or low concentrations of collagen (0.6 μg/ ml) in PRP were completely abolished by PALP (24 mM), TFPZ (250 μM) as well as indomethacin (10 μM). At higher concentrations of collagen (10–15 μg/ml) in PRP and WPL, the use of stirred and unstirred platelets treated with collagen enabled a distinction to be made between aggregation and adhesion- mediated release reaction. Platelet aggregation and the aggregation-mediated release reaction induced by these concentrations of collagen in stirred platelets were completely abolished by PALP, TFPZ and indomethacin although neither adhesion to collagen nor the adhesion-mediated release reaction of unstirred platelets was significantly affected by these inhibitors. Interestingly, both adhesion and the adhesion-mediated release reaction were abolished by concentrations of PALP 10–40 fold higher than those required to abolish aggregation. Collagen-induced platelet aggregation, but not platelet adhesion, was inhibited in resuspended platelets pretreated with PALP and NaBH4 indicating a separation in the membrane sites involved in aggregation and adhesion. The results further emphasize the distinction between adhesion and aggregation-mediated events with regards to collagen with the latter being more susceptible to inhibition by antiplatelet agents such as PALP and TFPZ.

Inhibitory Effect of Piracetam on Platelet-rich Thrombus Formation in an Animal Model

1998 ◽  
Vol 79 (01) ◽  
pp. 222-227 ◽  
Author(s):  
F. Stockmans ◽  
W. Deberdt ◽  
Å. Nyström ◽  
E. Nyström ◽  
J. M. Stassen ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ex Vivo ◽  
Peak Plasma ◽  
Thrombus Formation ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Cell Deformability

SummaryIntravenous administration of piracetam to hamsters reduced the formation of a platelet-rich venous thrombus induced by a standardised crush injury, in a dose-dependent fashion with an IC50 of 68 ± 8 mg/kg. 200 mg/kg piracetam also significantly reduced in vivo thrombus formation in rats. However, in vitro aggregation of rat platelets was only inhibited with piracetam-concentrations at least 10-fold higher than plasma concentrations (6.2 ± 1.1 mM) obtained in the treated animals. No effects were seen on clotting tests.In vitro human platelet aggregation, induced by a variety of agonists, was inhibited by piracetam, with IC50’s of 25-60 mM. The broad inhibition spectrum could be explained by the capacity of piracetam to prevent fibrinogen binding to activated human platelets. Ex vivo aggregations and bleeding times were only minimally affected after administration of 400 mg/kg piracetam i.v. to healthy male volunteers, resulting in peak plasma levels of 5.8 ± 0.3 mM.A possible antiplatelet effect of piracetam could be due to the documented beneficial effect on red blood cell deformability leading to a putative reduction of ADP release by damaged erythrocytes. However similarly high concentrations were needed to prevent stirring-induced “spontaneous” platelet aggregation in human whole blood.It is concluded that the observed antithrombotic action of piracetam cannot satisfactorily be explained by an isolated direct effect on platelets. An additional influence of piracetam on the rheology of the circulating blood and/or on the vessel wall itself must therefore be taken into consideration.

The Inhibitory Effect Of Dilazep On Adhesion And Aggregation Of Platelet Following Aortic Intimal Injury In Rabbit

1981 ◽  
Author(s):  
A Sumiyoshi ◽  
T Hayashi ◽  
M Fujii
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
Endothelial Injury ◽  
Platelet Adhesion And Aggregation ◽  
Injured Area ◽  
Polyethylene Tubing

The inhibitory effect of dilazep and aspirin on in vivo platelet adhesion and aggregation in rabbit aorta subjected to endothelial injury was investigated. Endothelial injury was induced by insertion of polyethylene tubing from the femoral artery into the aorta. In the beginning before surgery, experimental animals were intravenously given sufficient drug to inhibit platelet aggregation in vitro in response to ADP and collagen. For a quantitative analysis of platelet accumulation on the damaged aortas, 51Cr-labeled platelets were used. For morphological study, the aortas were fixed by perfusion at one hour after injury and examined by light and scanning electron microscopy for platelet adhesion and aggregation in injured area.Radioactivity of damaged aortas in rabbits administered dilazep (50 or 100 μg/kg) or aspirin (10 mg/kg) was significantly lower than in rabbits untreated by drug. Dilazep and aspirin did not prevent completely the adherence of platelets on injured area of the aorta, but inhibited considerably the platelet aggregation to form raised platelet thrombus.

GUARANA (Paullinia cupana) INHIBITS AGGREGATION IN WHOLE BLOOD

1987 ◽  
Author(s):  
D A F Chamone ◽  
M Ivany-Silva ◽  
C Cassaro ◽  
G Bellotti ◽  
C Massumoto ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Oral Intake ◽  
Inhibitory Effect ◽  
Impedance Method ◽  
Paullinia Cupana ◽  
Induced Aggregation

Guarana, a methylxanthine obtained from the seeds of Paullinia cupana has been largely used in the Amazon region by native indians during centuries as stimulant. We evaluated the effect of guarana on ex-vivo and in vitro platelet aggregation induced by adenosine-5-diphosphate (ADP) in human and rat whole blood with an impedance (Chrono-Log, model 500) and in their platelet rich plasma (PRP) with an optical aggregometer (Chrono-Log, model 440). Ex-vivo studies were carried out after single oral intake of guarana. Seven healthy volunteers (5 male and 2 female) aged 19-26 years who had taken no drugs for 10 days before, ingested 8gm of crude powder of guarana. Blood samples were drawn before and 1 hour after guarana intake. We observed a significative inhibition of platelet aggregation in whole blood meanwhile PRP was un changed as compared to basal values. In vitro studies were performed in whole blood and PRP from human volunteers and male Wis-tar rats. The combined effect of guarana and adenosine was also studied. A control aggregation was always run with saline. The results demonstrated an inhibition statistically significative (p < 0.001) of platelet aggregation in whole blood. Differently from whole blood the PRP with the same concentration of guarana did not result in inhibition of ADP induced aggregation when eva luated with the impedance method. The blood incubation with adenosine and guarana resulted in synergistic inhibitory effect that was much more strinking in whole blood than in PRP. Guarana fails to inhibit aggregation of rat platelets.Our results demonstrate that guarana prevents platelet aggregation in whole blood which depends on red blood cells, probably involving adenosine.

Lu 23051, A New Potent Inhibitor Of Platelet Aggregation

1981 ◽  
Author(s):  
H D Lehmann ◽  
J Gries ◽  
D Lenke
Keyword(s):  
Platelet Aggregation ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Coronary Vessels ◽  
Inhibitory Effect ◽  
Spontaneously Hypertensive ◽  
Dependent Inhibition ◽  
Induced Aggregation

6- [p-(2-(Chiorpropionylamino)phenyl] -4.5-dihydro-5-methyl-3(2H)-pyridazinone, LU 23051, is primarily characterized by its strong inhibition of platelet aggregation under in vitro and in vivo conditions. In vitro there is a concentration-dependent inhibition of ADP and collagen induced aggregation in platelet rich plasma of man, rat and dog. The inhibitory concentration EC 33 % is 0.0010-0.030 mg/1 (man: ADP-0.030, col 1.-0.013 mg/l) depending on species and type of aggregation. When administered orally in ex vivo experiments on rats and dogs the substance is found to have a dose-dependent antiaggregatory effect in the range from 0.1-3.16 mg/kg. The ED 33 % is 0.27-0.63 mg/kg.-In addition after oral administration the substance has a good inhibitory effect in models being based on intravascular platelet aggregation. Thus, a dose of 1 mg/kg inhibits laser-induced aggregation in mesenteric venules of rats. Mortality after i.v. injection of collagen in mice is reduced by 50 % after a dose of 0.02 mg/kg. A dose of 0.039 mg/kg prolongs the bleeding time of rats by 50 %. The aggregation-inhibiting action is of long duration (0.1 mg/kg p.o.∼24 h). The substance does not interfere with clotting.Besides its effect on platelet aggregation LU 23051 acts as vasodilatator as well. Dilatation of coronary vessels by 100 % is seen in isolated guinea-pig hearts at a concentration of 0.1 mg/l. In spontaneously hypertensive rats the substance has an anti hypertensive effect. The ED 20 % is 0.36 mg/kg p.o.The combination of antiaggregatory and vasodilatatory effects opens up interesting aspects with respect to the pharmacotherapeutic use of the new substance

THE PLATELET ANTIAGGREGATORY EFFECT OF ILOPROST IS ENHANCED BY ASPIRIN:IN VITRO AND EX VIVO STUDIES IN HUMAN SUBJECTS.

1987 ◽  
Author(s):  
E Tremoli ◽  
P Maderna ◽  
S Colli ◽  
L Mannucci ◽  
C R Sirtori ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Human Subjects ◽  
Selective Inhibition ◽  
Blood Collection ◽  
Inhibition Of Platelet Aggregation ◽  
Iloprost Infusion

To evaluate whether the activity of Iloprost, a chemically stable prostacyclin analog, on platelet aggregation could be potentiated by aspirin (ASA), in vitro and ex vivo studies in human volunteers were performed. In vitro studies were carried out in human platelet rich plasma (PRP) incubated with different concentrations of ASA (25-150 μM). For ex vivo studies Iloprost (0.5 ng.Kg−1.min−1 for 30 min) was given intravenously to healthy volunteers. After 20 hour wash out a single 50 mg ASA dose was given to the same subjects. Two hours after ASA intake, a second infusion of Iloprost was carried out. Blood was collected at appropriate time intervals thereafter. Platelet aggregation and thromboxane B2 (TXB2) formation were determined in collagen stimulated PRP. ASA, in vitro , dose dependently reduced the concentrations oF Iloprost required to achieve 50% inhibition of platelet aggregation (IC50) in PRP stimulated by 1 g/ml collagen. Also, the IC50S for Iloprost were significantly reduced (p<0.01) in PRP of subjects who ingested ASA two hours before blood collection. Iloprost infusion (0.5 ng.Kg−1.min−1 for 30 min) only minimally affected the concentrations of collagen eliciting 50% aggregation (AC50) and was ineffective on TXB2 synthesis. ASA, administered after a 20 hour wash out period did not significantly affect the AC s for collagen, whereas it inhibited TXB2 synthesis by more than 50%. The mean AC50 for collagen, evaluated at the end of Iloprost infusion in PRP of subjects who previously ingested ASA, was signicantly greater than that evaluated after the two single treatments. No significant changes in hemodynamic and ECG parameters were detected during the study. These findings, indicating an in vivo potentiating effect of ASA on the antiaggregatory activity of Iloprost, observed at doses of Iloprost with no effect on hemodynamic parameters, may be of relevance for the design of treatment schedules aimed to the selective inhibition of platelet aggregation.

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