Effects of dipyridamole and low-dose aspirin therapy on platelet adhesion to vascular subendothelium

Lauri, D; Zanetti, Adriana; Dejana, Elisabetta; Gaetano, Giovanni de

doi:10.1016/0002-9149(86)90394-2

Cited by 20 publications

(4 citation statements)

References 17 publications

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“…Howver, aspirin failed to exhibit a significant activity against platelet adhesion. The results are consistent with a previous report showing that aspirin did not inhibit human platelet adhesion to denuded rat thoracic aorta ex vivo [22], Lines of evidence suggest that cGMP regu lates both platelet adhesion and aggregation. However, the mcchanism(s) by which cGMP modulates platelet function is not clearly un derstood.…”

Section: Discussionsupporting

confidence: 93%

In vivo Inhibition of Platelet Adhesion by a cGMP-Mediated Mechanism in Balloon Catheter Injured Rat Carotid Artery

et al. 1996

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The role of cyclic guanosine monophosphate (cGMP) versus cyclic adenosine monophosphate (cAMP) mediated mechanism in modulating platelet adhesion was investigated in balloon catheter injured rat carotid arteries. Vascular injury with balloon angioplasty significantly increased the adherence of platelets to the injured carotid arteries. Intravenous infusion of zaprinast (1 mg/kg/min), a cGMP phosphodiesterase inhibitor, or sodium nitroprusside (8 µg/kg/min), a stimulator of soluble guanylate cyclase, significantly attenuated the adherence of platelets to the injured carotid arteries. In comparison, infusion of milrinone, acAMP phosphodiesterase inhibitor, or 8-bromo-cAMP failed to affect the platelet deposition in the injured carotid arteries. Nifedipine or aspirin also failed to attenuate the adherence of platelets to the injured carotid arteries. In conclusion, agents known to elevate intracellular platelet cGMP but not cAMP appear to afford the most effective protection in vivo against the adhesion of platelets to the vessel wall without intact endothelium.

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Section: Discussionsupporting

confidence: 93%

In vivo Inhibition of Platelet Adhesion by a cGMP-Mediated Mechanism in Balloon Catheter Injured Rat Carotid Artery

et al. 1996

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“…19 Studies in vitro and ex vivo have found that dipyridamole significantly reduces platelet adhesion to vascular sub-endothelium although the mechanism remains unclear. 20,21 Both vWf and P-selectin are stored in Weibel-Palade body in the endothelium. 22,23 Proinflammatory mediators activate cells causing Weibel-Palade bodies to fuse with the cell membrane resulting in the release of vWf and surface exposure of P-selectin.…”

Section: Discussionmentioning

confidence: 99%

Effect of aspirin, clopidogrel and dipyridamole on soluble markers of vascular function in normal volunteers and patients with prior ischaemic stroke

et al. 2006

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A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk IL-6 also increases endothelial production of the fibrinolytic inhibitor, plasminogen activator inhibitor type 1 (PAI-1). We assessed the effects of aspirin, clopidogrel and dipyridamole on a panel of the above soluble markers of vascular function in normal volunteers and patients with a prior history of ischaemic stroke. We also assessed the effect of combining the three antiplatelet agents on the soluble markers since we have shown previously that three drugs may be superior to one or two in inhibiting platelet function in vitro. 15Page 4 of 15 METHODS DesignTwo randomised, outcome-blinded, multiway, crossover trials of antiplatelet therapy were performed in normal volunteers and patients with prior ischaemic stroke. The study design has been published previously 16 in a report of the effect of aspirin, clopidogrel and dipyridamole on the function of circulating platelets, phagocytes and their conjugates. SubjectsThe study protocol was approved by the local Research Ethics Committee. All subjects gave written informed consent and the trials were performed according to the that complete data were present for each person; laboratory data from withdrawing subjects are not included in the statistical analyses. Laboratory studySerum and plasma collected into 3.8% sodium citrate (1:9 volume) or 4.0 mmol/L EDTA were centrifuged (1,500g for 15min) within 1 hour of venepuncture. Aliquots were frozen at -80 o C and then assayed in batches using commercially available ELISA kits. CRP (high sensitivity kit, Kalon Biological, Hants, UK) and PDGF (R&D System, Abington, UK) were measured in serum; cGMP (R&D System), vWf (Corgenix, Cambridgeshire, UK), MCP-1 (R&D System) and PAI-1 (Technoclone TC, Surrey, UK)were analysed in citrated plasma. Statistical analysisThe primary analysis compared the presence and absence of each drug on soluble markers, i.e. aspirin versus no aspirin, clopidogrel versus no clopidogrel, and dipyridamole versus no dipyridamole. Secondary analyses compared triple therapy (ACD) versus all other drugs, as before. 16 Analyses were performed using the SAS statistical package.Page 6 of 15 RESULTSDemographic and clinical information for the subjects are given in table 1. The stroke patients are representative of our clinical stroke service and were significantly older and had more risk factors (more hypertension and smokers, higher systolic blood pressure, and elevated total cholesterol) than the volunteers (all p<0.05).When considering the individual effects of the three antiplatelet agents on soluble markers of vascular function, three observations were made. First, dipyridamole significantly reduced plasma vWf levels in ...

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“…In a singleblind, cross-over ex vivo study (Escolar et al, 1985) the combination of dipyridamole (75 mg three times daily) with acetylsalicylic acid (50 mg three times daily) showed the strongest inhibition of the formation of larger thrombi in I 1 -,' 7 0 d-4-dl comparison with the single drugs. Treatment with dipyridamole (75 mg twice daily) alone or combined with low-dose acetylsalicylic acid (25 mg twice daily) reduced platelet adhesion to denuded rat aorta in a single-blind, cross-over study (Lauri et al, 1986). In the present study dipyridamole affected neither the total number of platelets/aggregates nor the number of single platelets and very small aggregates (area class 1) identified on the subendothelial matrix.…”

Section: Discussionmentioning

confidence: 99%

Dipyridamole alone or combined with low‐dose acetylsalicylic acid inhibits platelet aggregation in human whole blood ex vivo [see comments]

Müller¹,

Su²,

Weisenberger³

et al. 1990

Brit J Clinical Pharma

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1. In a randomized, double‐blind trial we compared the inhibition of the platelet‐vessel wall interactions in whole blood ex vivo. There were four groups of 24 healthy volunteers each of whom were treated orally for 3.5 days with either 200 mg dipyridamole (sustained release preparation), 25 mg acetylsalicylic acid, both drugs combined or placebo twice daily. 2. The mean area of all platelets/aggregates was reduced by 6.2% +/− 4.2% (+/− s.e. mean) by placebo (n = 23), 19.8% +/− 6.7% by dipyridamole (n = 22), 53.7% +/− 4.9% by acetylsalicylic acid (n = 23) and 71.4% +/− 3.7% by the combination of both drugs (n = 24), when compared with total inhibition of aggregation by EGTA. Thus, low‐ dose acetylsalicylic acid inhibited aggregation (P less than 0.001). 3. Dipyridamole reduced the size of platelet aggregates (P less than 0.01, two‐fold analysis of variance). The reduction was correlated with the individual dipyridamole plasma levels (P less than 0.05, analysis of covariance). The subgroup of large and very large thrombi being formed was also reduced by dipyridamole (P less than 0.05). 4. This ex vivo study demonstrates that dipyridamole alone inhibits formation of thrombi on subendothelial matrix and enhances the inhibitory effect of low dose acetylsalicylic acid in this model of thrombosis.

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Effects of dipyridamole and low-dose aspirin therapy on platelet adhesion to vascular subendothelium

Cited by 20 publications

References 17 publications

In vivo Inhibition of Platelet Adhesion by a cGMP-Mediated Mechanism in Balloon Catheter Injured Rat Carotid Artery

In vivo Inhibition of Platelet Adhesion by a cGMP-Mediated Mechanism in Balloon Catheter Injured Rat Carotid Artery

Effect of aspirin, clopidogrel and dipyridamole on soluble markers of vascular function in normal volunteers and patients with prior ischaemic stroke

Dipyridamole alone or combined with low‐dose acetylsalicylic acid inhibits platelet aggregation in human whole blood ex vivo [see comments]

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