Increased prostacyclin production during exercise in untrained and trained men: effect of low-dose aspirin

1995 ◽  
Vol 78 (5) ◽  
pp. 1832-1838 ◽  
Author(s):  
R. H. Boger ◽  
S. M. Bode-Boger ◽  
E. P. Schroder ◽  
D. Tsikas ◽  
J. C. Frolich
Keyword(s):  
Platelet Aggregation ◽  
Prostaglandin E2 ◽  
Low Dose ◽  
Submaximal Exercise ◽  
Trained Subjects ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Before And After ◽  
Excretion Rates ◽  
Prostacyclin Production

The influence of a submaximal exercise on urinary 2,3-dinor-6-ketoprostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha), 2,3-dinor-thromboxane B2 (2,3-dinor-TxB2), and prostaglandin E2 excretion and on platelet aggregation was compared in untrained and trained subjects before and after low-dose aspirin administration (50 mg/day, 7 days). 2,3-Dinor-TxB2 excretion was significantly higher in the athletes at rest (P < 0.05). Submaximal exercise selectively increased 2,3-dinor-6-keto-PGF1 alpha excretion without affecting 2,3-dinor-TxB2 or prostaglandin E2 excretion rates or platelet aggregation. Low-dose aspirin inhibited platelet aggregation and 2,3-dinor-TxB2 excretion but reduced 2,3-dinor-6-keto-PGF1 alpha by only 24% in the untrained and by 51% in the trained subjects (P < 0.05). After low-dose aspirin administration, the selective stimulatory effect of submaximal exercise on urinary 2,3-dinor-6-keto-PGF1 alpha excretion was even more pronounced than before. The ratio of 2,3-dinor-6-keto-PGF1 alpha to 2,3-dinor-TxB2 was increased by exercise; this effect was significantly enhanced by low-dose aspirin (P < 0.05). Our results suggest that the stimulatory effect of submaximal exercise on prostacyclin production is mostly due to an activation of prostacyclin synthesis from endogenous precursors rather than the result of an enhanced endoperoxide shift from activated platelets to the endothelium. This effect is potentiated by low-dose aspirin pretreatment, indicating that 50 mg/day of aspirin do not impair exercise-induced endothelial prostacyclin production.

EVALUATION ON EFFECTIVENESS OF LOW DOSE ASPIRIN THERAPY FOR PROTECTION OF THROMBUS FORMATION

1987 ◽  
Author(s):  
S Kariyone ◽  
M Hirakuri ◽  
T Yui ◽  
T Uchida
Keyword(s):  
Platelet Aggregation ◽  
Oral Dose ◽  
Time Course ◽  
Low Dose ◽  
Thrombus Formation ◽  
Platelet Factor ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Before And After

In order to protect thrombus formation, administration of low dose aspirin has become common. However, its significance for this purpose is still not clear. Effect of small dose of aspirin (ASA) onplatelet aggregation and ability of malondialdehyde(MDA) formation in platelet by the addition of arachidonic acid in vitro were investigated. In clinical study, platelet aggregation, MDA formation of platelet, serum P-thromboglobulin(p-TG), platelet factor 4(PF4) and thromboxane B2(TX-B2) levelswere measured before and after low doseaspirin therapy.Platelet aggregations by ADP, collagen, epinephrin and arachidonate as inducers were significantly suppressed under 12.5 ug/ml ASA in the medium. MDA formation of platelet was remarkably inhibited under 1.6 ug/ml of ASA in the medium in vitro.In patients, single oral dose of 50 mg ASA showed no change on platelet aggregation while the ability of MDA formation decreased 50# of the before. Serum concentration of ASA after oral dose of 50 mg ASA only showed 1.5 to 6.0 ug/ml at maximum.Daily dose of 50 mg ASA was continued during 10 days. Changes of various factors due to the time course were observed. Inhibitions of platelet aggregation were seen from 5th day on ADP and collagenand from 2nd day on epinephrin and arachidonate as inducers during the therapy. MDA formations of platelet were decreased quickly and it became almost zero at 5th day. ASA levels in the patient serum reached plateau as 8 or 9 ug/ml from 3rdday.Various patients with a possibility of thrombus formation were administered daily 50 mg ASA during 10 days. Platelet aggregations and MDA production, serum β-TG, PF4 and TXB2 levels were measured before and after the therapy. Platelet aggregations by ADP, collagen and epinephrin as inducers were significantly suppressed after the therapyand MDA production of platelet was also markedly decreased after the therapy. There were no significant changes in serumβ-TG and PF4 levels while TXB2 level tended to decrease after the therapy.From these results, it was concluded that daily 50 mg ASA oral dose was certainly effective for protection of thrombus formation.

scholarly journals Effect of low-dose aspirin on platelet aggregation inhibition in patients with rheumatoid arthritis

2019 ◽  
Vol 7 (4) ◽  
pp. 110-117
Author(s):  
Mehrzad Hajialilo ◽  
Amir Ghorbanihaghjo ◽  
Forough Ghassemi ◽  
Alireza Khabbazi ◽  
Aida Malek Mahdavi
Keyword(s):  
Rheumatoid Arthritis ◽  
Platelet Aggregation ◽  
Low Dose ◽  
Enzyme Linked Immunosorbent Assay ◽  
American College Of Rheumatology ◽  
Dose Aspirin ◽  
Framingham Risk ◽  
Low Dose Aspirin ◽  
Before And After ◽  
Artery Disease

Introduction : The risk for coronary artery disease (CAD) and mortality has increased in patients with rheumatoid arthritis (RA). Aspirin has anti-thrombotic effects and causes reduction in CAD occurrence in high-risk individuals. The objective of present project was evaluating the influence of low-dose aspirin on inhibition of platelet aggregation in patients with RA. Methods: Forty-eight subjects with RA diagnosed based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria and age- and sex-matched healthy participants were studied. All subjects received 81 mg/day aspirin for 10 days. Level of the serum thromboxane B2 (sTxB2), a permanent metabolite of thromboxane A2 (TxA2), was measured before and after therapy using enzyme-linked immunosorbent assay (ELISA) kit. The impotency to decrease sTxB2 production to less than 10 ng/ml indicates suboptimal suppression of platelet aggregation via aspirin. Results: Low-dose aspirin decreased sTxB2 significantly compared with baseline in patients with RA [median interquartile range (IQR): 25.72 (11.78, 90.10) to 7.74 (5.80, 8.82), P < 0.001] and in healthy controls [median (IQR): 40.50 (33.25, 50.90) to 7.30 (4.75, 8.85), P < 0.001]. No remarkable changes were seen in sTxB2 between patients and controls after adjustment (P > 0.050). Pharmacologic influence of aspirin was suboptimal in 6.25% of cases in the presence of higher erythrocyte sedimentation rate (ESR) and in 2.7% of controls. Low-dose aspirin decreased sTxB2 significantly only in patients with Framingham Risk Score (FRS) < 10%. Conclusion: Low-dose aspirin decreased sTxB2 level and suppressed platelet aggregation and therefore, was effective in primary prevention of cardiovascular (CV) events in patients with RA; however, additional studies are required to reach accurate conclusions.

Effects of low-dose aspirin on in vitro platelet aggregation in the early minutes after ingestion in normal subjects

1994 ◽  
Vol 74 (7) ◽  
pp. 720-723 ◽  
Author(s):  
Salim F. Dabaghi ◽  
Suraj G. Kamat ◽  
John Payne ◽  
Gary F. Marks ◽  
Robert Roberts ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Low Dose ◽  
Normal Subjects ◽  
Dose Aspirin ◽  
Low Dose Aspirin

The Effect Of Low Dose Aspirin On Human Venous Prostacyclin Production And Platelet Thromboxane Synthesis

1981 ◽  
Author(s):  
S P Hanley ◽  
J Bevan ◽  
S Cockbill ◽  
S Heptinstall
Keyword(s):  
Vessel Wall ◽  
Low Dose ◽  
Varicose Veins ◽  
Normal Volunteers ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Radio Immunoassay ◽  
Prostacyclin Production ◽  
Specific Radio ◽  
Platelet Thromboxane

This study vas undertaken to determine if there was a dose of oral aspirin that would inhibit platelet cyclooxygenase but that had no effect on venous cyclo-oxygenase. Varicose veins were surgically removed from 68 patients of whom 21 had taken no medicines pre-operatively. Three groups of patients took aspirin 300 mg 14 hours (n=10), 24 hours (n=10) and 48 hours (n=9) pre-operatively. Two other groups took 40.5 mg (n=9) and 81 mg (n=9) 14 hours preoperatively. Two 6 mm discs of venous tissue were incubated with plasma that contained 1 mM sodium arachidonate (NaAA) and the anti-aggregatory activity of the plasma was compared with that of synthetic PGI2 in aspirinised citrated PRP challenged with ADP. PGI2 production in this procedure was confirmed by specific radio-immunoassay for 6-keto PGF1α. All doses of aspirin except 40.5 mg markedly inhibited PGI2 synthesis. Little recovery was seen with 300 mg at 48 hour post-drug.Five normal volunteers took aspirin 300 mg and 5 others 40.5 mg. Citrated PRP was prepared immediately before, 2, 24, 48, 96 and 192 hours after ingesting the drug. The amount of malondialdehyde (MDA, a marker for thromboxane synthesis) that was produced when 1 mM NaAA was added, was markedly reduced compared to the control at 2 and 24 hours by both 40.5 mg and 300 mg and thereafter it returned slowly to control values. This study indicates that 40.5 mg of aspirin inhibits platelet cyclo-oxygenase but not vessel wall cyclo-oxygenase.

Effects of Combining Aspirin with Non-Steroidal Anti-Inflammatory Drugs or COX-2 Inhibitors on Shear-Induced Platelet Aggregation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1853-1853
Author(s):  
Angela Bergeron ◽  
Carol Sun ◽  
Jennifer Wood ◽  
Jo Ellen Schweinle ◽  
Frank L. Lanza ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Naproxen Sodium ◽  
Low Dose ◽  
Closure Time ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Inflammatory Drugs ◽  
The Mean ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Abstract Aspirin has been widely used as a cardiac protective drug, often with hemostasis inhibition and bleeding risks. This concern becomes even more significant when it is used in combination with non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors, both of which may have independent effects on platelets. To study how hemostasis may be affected by these drugs, we conducted a multiple-dose, single-blind, parallel-group study to determine the effects of aspirin combined with over-the-counter NSAIDs or COX-2 inhibitors on shear-induced platelet aggregation (SIPA). For this study, 87 healthy individuals (age 40 to 75) who met inclusion and exclusion criteria were recruited. All subjects received 81 mg of aspirin (non-enteric coated and chewable) daily for eight days. In addition, beginning 2 hours after low-dose aspirin, the subjects also received one of the following drugs: acetaminophen (4 doses of 1000 mg daily), ibuprofen (3 doses of 400 mg daily), naproxen sodium (440 mg morning and 220 mg evening), additional aspirin (4 doses of 650 mg daily), celecoxib (2 doses of 200 mg daily) and rofecoxib (1 dose of 25 mg daily). The second drugs were given 2 hrs after initial aspirin intake. The control group received only 81 mg of aspirin. Blood was drawn before the treatment and at 24 hr and 7 days (before any medications on Day 8) after the initial drug intake. Shear-induced platelet aggregation (SIPA) on a collagen matrix with either ADP or epinephrine was measured in citrated whole blood using a platelet function analyzer. The aggregation was defined as closure time (sec) under a constant shear rate of 1500 −s, a level of pathological high shear stress. We found that the closure time with the collagen/ADP cartridge was not affected by any of the treatments (83 – 108 sec). In contrast, SIPA with the collagen/epinephrine cartridge showed a time-dependent inhibition by 81 mg of aspirin with the mean closure times being 118, 138, and 222 sec before drug administration, 24 hr and 7 day after treatments, respectively. The course of low-dose aspirin inhibition of SIPA was not changed by acetaminophen, celecoxib, or rofecoxib. In contrast, the mean closure time at 24 hr after the treatment was 249 and 264 sec for samples from individuals on a combined treatment of low-dose aspirin with either naproxen sodium or a high dose of aspirin (2600 mg), significantly longer than those of other treatment groups (P< 0.001). It has been demonstrated that SIPA, which is primarily initiated by the GP Ib-VWF interaction, is insensitive to aspirin. Our results suggest that aspirin inhibits SIPA induced in the presence of collagen and epinephrine, but not collagen and ADP. Furthermore, this effect was significantly enhanced by either naproxen sodium or a higher dose of aspirin (2600 mg), suggesting that the simultaneous intake of low-dose aspirin and either analgesic doses of aspirin or naproxen may enhance the risk of aspirin-induced bleeding tendency.

Effects of Non-Steroidal Anti-Inflammatory Drugs and COX-2 Inhibitors on Aspirin-Induced Platelet Inhibition.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 531-531
Author(s):  
Carol Sun ◽  
Angela Bergeron ◽  
Jennifer Wood ◽  
Jo Ellen Schweinle ◽  
Frank L. Lanza ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Naproxen Sodium ◽  
Low Dose ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Enteric Coated ◽  
Cox 2 Inhibitors ◽  
Initial Drug

Abstract Low dose aspirin has been widely used as a cardiac protective drug. It acts by inhibiting platelet activation and aggregation through the cyclooxygenase-1 pathway. However, such effects may be affected by short-term use of other drugs such as non-steroidal anti-inflammatory drugs (NSAIDs). We have conducted a multiple-dose, single-blind, parallel-group study to investigate the effects of over-the-counter NSAIDs and COX-2 inhibitors on arachidonic-induced platelet aggregation and thromboxane B2 (TxB2) production. We recruited 87 healthy individuals of 40-75 years of age, who met the inclusion and exclusion criteria by pretest screening. All subjects received 81 mg of aspirin (non-enteric coated and chewable) daily for eight days. Two hours after the 81 mg aspirin dose, the subjects received one of following drugs: acetaminophen (4 doses of 1000 mg daily), ibuprofen (3 doses of 400 mg daily), naproxen sodium (440 mg morning and 220 mg evening), a higher dose of aspirin (4 doses of 650 mg daily), celecoxib (2 doses of 200 mg daily) and rofecoxib (1 dose of 25 mg daily). Control individuals received only 81 mg of aspirin. Citrated blood was obtained before the treatment and at 2, 6, 12, and 24 hr during the first day and an identical schedule after 7 days of dosing (Day 8 of treatment). Platelet function was measured by arachidonic acid-induced platelet aggregation and serum levels of TxB2. We found that the maximal inhibitory effect (more than 85% reduction in aggregation) of 81 mg aspirin was reached more than 24 hr after initial drug intake; whereas it was observed within 6 hr in subjects receiving randomized 2600 mg of aspirin (but only took 1300 mg at time of blood draw). Similar to the higher dose of aspirin, both ibuprofen and naproxen sodium also significantly accelerated the inhibitory effects of low dose aspirin on platelet aggregation (Paired Student t test, p &lt; 0.01). In comparison, acetaminophen and two COX-2 inhibitors showed no additive effects with 81 mg of aspirin. Consistent with aggregation studies, the inhibition of TxB2 production was significantly greater than those with 81 mg of aspirin only at 6, 12, and 24 hr after initial drug intake for 2600 mg of aspirin, ibuprofen, and naproxen, but not for acetaminophen, celecoxib, and rofecoxib. Contrary to a report by Catella-Lawson et al, we found that ibuprofen did not interfere, but rather slightly enhanced, aspirin-induced inhibition of platelet aggregation. The reason for the discrepancy remains unknown, but may be attributed to the type of aspirin used (enteric-coated vs. non-enteric-coated) and different schedules of drug intakes between the two studies. Finally, it may also be due to the fact that our subjects were in their normal environments and not in a clinical research unit. In conclusion, we found that acetaminophen and COX-2 inhibitors did not affect the course of the low-dose aspirin action on platelets. Although ibuprofen and naproxen have had no additive effects, they accelerated the action of 81 mg of aspirin on platelet aggregation.

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