Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ASPIRIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed1992

Arachidonic acid metabolism in monocytes of aspirin-sensitive asthmatic patients before and after oral aspirin challenge.

Aspirin and nonsteroidal antiinflammatory drugs induce bronchospastic reactions in patients with aspirin-sensitive respiratory disease. Although the mechanism of this reaction is unknown, all drugs that induce the respiratory reaction also inhibit the cyclooxygenase enzyme. The ensuing changes in arachidonate metabolism are presumed to play a role in the pathogenesis of the reaction. We measured generation of leukotrienes and thromboxane by calcium ionophore stimulated blood monocytes. Before aspirin challenge, monocytes released significantly more thromboxane B2 in patients with aspirin sensitivity than in patients without aspirin sensitivity or in healthy control subjects (p < 0.02). During aspirin-induced bronchospasm, release of leukotriene B4 increased significantly (45.5%, p = 0.018), whereas release of thromboxane B2 decreased (-46.9%, p = 0.028). Two hours after ingestion of 60 mg aspirin, normal monocyte release of thromboxane B2 did not drop, whereas leukotriene B4 release increased. Monocytes formed only minimal amounts of leukotriene C4. We conclude that the profile of released eicosanoids from aspirin-sensitive monocytes is distinct from non-aspirin-sensitive subjects, and that these differences could contribute to the development of bronchospasm after aspirin ingestion.

Administration, Oral↗
PubMed2005

Expression of the cysteinyl leukotriene receptors cysLT(1) and cysLT(2) in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis.

BACKGROUND: Cysteinyl leukotrienes play a disease-regulating role in rhinosinusitis and asthma, particularly aspirin-sensitive disease. They act through 2 G-protein coupled receptors termed cysteinyl leukotriene type 1 receptor (cysLT 1 ) and cysteinyl leukotriene type 2 receptor (cysLT 2 ). We previously compared expression of cysLT 1 on mucosal leukocytes in patients with aspirin-sensitive and aspirin-tolerant rhinosinusitis. OBJECTIVE: To compare expression of cysLT 1 and cysLT 2 on leukocytes, mucus glands, and epithelium in 32 patients with chronic polypoid rhinosinusitis (21 aspirin-sensitive, 11 aspirin-tolerant) and 9 normal controls. METHODS: Total numbers of CD45 + leukocytes, percentages of these cells expressing cysLT 1 or cysLT 2 , and percentages of the total epithelial and glandular areas expressing cysLT 1 or cysLT 2 were measured in sections of nasal biopsies by using immunohistochemistry and image analysis. RESULTS: The percentages of mucosal CD45 + leukocytes expressing cysLT 1 were significantly ( P < .0001) elevated in the aspirin-sensitive but not the aspirin-tolerant patients compared with the controls. In contrast, the percentages of leukocytes expressing cysLT 2 did not differ significantly in the 3 groups. On epithelial and glandular cells, expression of cysLT 2 significantly exceeded that of cysLT 1 in both the patients with rhinosinusitis and the controls ( P < or = .004), although there was no significant difference in the expression of either receptor in the patients with rhinosinusitis (aspirin-sensitive or aspirin-tolerant) and the controls. CONCLUSION: Although cysLT 1 expression predominates on inflammatory leukocytes in patients with aspirin-sensitive rhinosinusitis, the effects of cysteinyl leukotrienes on glands and epithelium may be mediated predominantly through cysLT 2. This has potentially important therapeutic implications.

Adult↗
PubMed2003

Aspirin modifies nitric oxide synthase activity in platelets: effects of acute versus chronic aspirin treatment.

OBJECTIVE: We examined the effects of aspirin on basal and beta-adrenoceptor (beta-AR)-mediated nitric oxide synthase (NOS) activity in normal platelets. METHODS: NOS activity was determined from the conversion of L-[3H]arginine to L-[3H]citrulline, both basally and following beta-AR stimulation, in platelets from healthy human subjects following both short- and long-term aspirin administration. RESULTS: Basal L-[3H]citrulline increased following aspirin 800 mg administered intravenously in vivo, from 0.31+/-0.12 to 0.76+/-0.14 pmol/10(8) platelets (P<0.01). Isoproterenol at 1 micromol/l increased platelet NOS activity before but not following intravenous aspirin. After short-term in vitro treatment with aspirin 10 micromol/l, 400 micromol/l or 4 mmol/l, basal platelet L-[3H]citrulline increased similarly, an effect not seen with indomethacin 100 micromol/l or ibuprofen 10 micromol/l. Platelet NOS activity was not increased by albuterol 1 micromol/l, in the presence of indomethacin, ibuprofen or aspirin in vitro. By contrast, oral aspirin 75 mg daily for 14 days did not affect basal platelet NOS activity, but abolished beta-adrenergic NOS activation. CONCLUSIONS: Aspirin activates basal platelet NOS acutely, but not chronically, through a mechanism independent of cyclooxygenase (COX) inhibition. By contrast, both short- and long-term aspirin treatment inhibit platelet beta-adrenergic NOS activation by a COX-dependent mechanism. This indicates that aspirin exerts divergent effects on basal and beta-AR-stimulated platelet NOS activity, which are likely to be of clinical relevance.

Adrenergic beta-Agonists↗
PubMed1995

Hydrocortisone sodium succinate does not cross-react with aspirin in aspirin-sensitive patients with asthma.

BACKGROUND: Bronchospasm after intravenous hydrocortisone treatment has been reported in some patients with aspirin-sensitive respiratory disease. OBJECTIVE: This study was designed to determine the prevalence of sensitivity to hydrocortisone among patients with aspirin-sensitive respiratory disease. METHODS: We performed double-blind, placebo-controlled challenges with aspirin and 100 mg of hydrocortisone sodium succinate administered intravenously in 53 subjects. RESULTS: Forty-five of the 53 subjects (85%) undergoing oral aspirin challenge experienced respiratory reactions to aspirin. Forty-four of these 45 patients had neither naso-ocular, cutaneous, nor respiratory reactions to hydrocortisone sodium succinate. One aspirin-sensitive subject had bronchospasm and a naso-ocular reaction to hydrocortisone sodium succinate and a naso-ocular reaction with minimal bronchospasm to methylprednisolone sodium succinate. After desensitization to aspirin, and while receiving maintenance aspirin therapy, this subject again reacted to hydrocortisone sodium succinate with bronchospasm and naso-ocular reaction. CONCLUSION: We conclude that aspirin-sensitive patients with asthma are not preferentially sensitive to hydrocortisone and that hydrocortisone sodium succinate does not cross-react or cross-desensitize with aspirin.

Adult↗
PubMed2006

Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.

BACKGROUND: Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty. METHODS: We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070). FINDINGS: Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache. INTERPRETATION: The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.

Aged↗
PubMed2001

Effects of pranlukast on aspirin-induced bronchoconstriction: differences in chemical mediators between aspirin-intolerant and tolerant asthmatic patients.

BACKGROUND: Aspirin inhibits cyclooxygenase activity and modifies production of the arachidonate cascade in aspirin-induced asthma. The aim of the present study was to examine the effects of leukotriene (LT) receptor antagonist on aspirin challenge on eosinophil activity and chemical mediators released into the airway of asthmatic patients. METHODS: Aspirin oral provocation test was performed in aspirin-intolerant asthmatic patients (AIA; N = 7) and aspirin-tolerant asthmatic patients (ATA; N = 7). In AIA, LT receptor antagonist (pranlukast) was administered orally 2 hours before the test, and its inhibitory effects on sputum LTC4+C4, eosinophil cationic protein (ECP), eosinophil count, urinary LTE4/creatinine (Cr), 11-dehydrothromboxane (11-dhTX) B2/Cr, serum LTC4+D4, ECP, and peripheral blood eosinophil count were compared with the findings in ATA subjects. RESULTS: In AIA, aspirin induced an immediate reaction associated with increased urinary LTE4/Cr and sputum ECP and a fall in urinary 11-dhTXB2/Cr. Pranlukast inhibited the bronchial reaction and an increase in sputum ECP after threshold dosed of ASA, but failed to change aspirin-induced LT production in sputum and urine. In ATA, aspirin challenge was only associated with a fall in urinary 11-dhTXB2. CONCLUSIONS: Our results indicated that aspirin-induced asthma is associated with overproduction of LT with a shift to the 5-lipoxygenase series of the arachidonate cascade and that leukotriene receptor antagonist are useful for AIA through inhibition of production of LT and eosinophilic inflammation in the airway.

Adult↗
PubMed2002

Inhibition of camel lens zeta-crystallin by aspirin and aspirin-like analgesics.

Camel lens zeta-crystallin was reversibly inhibited to various degrees by aspirin (acetyl salicylic acid) and the aspirin-like analgesics: paracetamol (acetaminophen) and ibuprofen (2-(4-isobutyl phenyl)-propionic acid). Among these, aspirin was the most potent inhibitor, causing nearly complete inhibition in a dose-dependent, but time-independent manner. Analysis of inhibition kinetics revealed that aspirin was uncompetitive inhibitor (K(i) 0.64 mM) with respect to NADPH and non-competitive inhibitor (K(i) 1.6 mM) with respect to the substrate, 9,10-phenanthrenequinone (PQ). Multiple-inhibition analysis showed that aspirin and pyridoxal 5' phosphate (PAL-P), a lysine specific reagent, simultaneously bound to a critical lysine residue located towards the NADPH binding region. Consistent with this, NADPH was able to substantially protect zeta-crystallin against aspirin, whereas PQ did not provide any protection. The results suggested that an essential lysine residue was the locus of aspirin binding. The inhibition of zeta-crystallin by aspirin and aspirin-like analgesics was reversible thus eliminating acetylation as a mechanism for inhibition. Reversible binding of aspirin to this lysine may cause steric hindrance resulting in uncompetitive inhibition with respect to NADPH.

Acetaminophen↗
PubMed2001

Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma.

BACKGROUND: Patients with aspirin-sensitive respiratory disease experience cross-reactions to all nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase enzymes. With the introduction of antiarthritis drugs, which selectively inhibit cyclooxygenase-2, questions are raised as to whether cross-reactivity occurs between aspirin and these new cyclooxygenase-2 inhibitors. OBJECTIVE: The goal of this study was to determine whether rofecoxib cross-reacts in aspirin-sensitive patients with asthma. METHODS: Sixty patients with asthma underwent doubleblinded, placebo-controlled oral challenges with rofecoxib (12.5 mg, 25 mg, and 2 placebos) over 48 hours in our General Clinical Research Center. The next day, aspirin sensitivity was proven in each of the 60 patients through use of single-blinded oral aspirin challenges. RESULTS: None of the 60 patients experienced any symptoms, changes in nasal examination findings, or declines in FEV(1) values during their challenges with rofecoxib. All 60 patients experienced typical naso-ocular and asthmatic reactions to aspirin with a mean provoking dose of 61 mg. The exact 1-sided CI for the probability of rofecoxib inducing crossreactions in aspirin-sensitive patients with asthma is calculated to be between 0% and 0.05%. CONCLUSION: Given that none of the 60 patients reacted to rofecoxib and given the statistical power of this large sample size, we conclude that cross-reactivity between aspirin and rofecoxib does not occur in patients with aspirin-sensitive respiratory disease. This does not exclude rofecoxib from participating in other types of reactions, including immune recognition after prior treatment with the drug. From the standpoint of the mechanisms involved in aspirin-induced respiratory reactions, this study strongly supports inhibition of cyclooxygenase-1 as the essential initiator of these types of reactions.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)

OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies). DESIGN: Randomised controlled trial. SETTING: Specialist clinic for recurrent miscarriages. SUBJECTS: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies. INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks' gestation. MAIN OUTCOME MEASURES: Rate of live births with the two treatments. RESULTS: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%). CONCLUSION: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.

Abortion, Habitual↗
PubMed1996

Effect of endobronchial aspirin challenge on inflammatory cells in bronchial biopsy samples from aspirin-sensitive asthmatic subjects.

BACKGROUND: The aspirin-induced bronchoconstriction in patients with aspirin-sensitive asthma is caused by cysteinyl leukotriene release. The cellular source of the leukotrienes is unknown. The inflammatory cell infiltrate in bronchial biopsy samples from seven aspirin-sensitive asthmatic (ASA) subjects and eight non-ASA subjects before and after local challenge with lysine aspirin was therefore examined. METHODS: Using flexible bronchoscopy, airway mucosal biopsy samples were taken and lysine aspirin solution was placed directly onto a carina of the contralateral lung. Twenty minutes later a second series of biopsy samples was taken from the site of the local endobronchial lysine aspirin challenge. The biopsy samples were double immunostained with a rabbit polyclonal antibody to the enzyme 5-lipoxygenase and monoclonal antibodies to mast cells (AA1), neutrophils (NP57), macrophages (EBM11), T lymphocytes (anti-CD3), and total (BMK13) and activated eosinophils (EG2). RESULTS: A decrease in both absolute mast cell numbers staining with mast cell tryptase (AA1) and the percentage of mast cells co-immunostaining with 5-lipoxygenase was seen in the ASA patients after lysine aspirin challenge compared with the non-ASA control group. There was also an increase in the numbers of activated eosinophils (EG2) in the ASA subjects compared with the non-ASA group. No changes were observed in the total numbers of macrophages (EBM11), neutrophils (NP57), total eosinophils (BMK13), and T lymphocytes (anti-CD3) after challenge with lysine aspirin. CONCLUSIONS: The decrease in numbers of mast cells staining for tryptase and the increase in activated eosinophils after endobronchial challenge with lysine aspirin may represent degranulation of these cell types, and may be an early event associated with aspirin-sensitive reactions in ASA subjects.

Administration, Topical↗
PubMed2004

Aspirin, but not NO-releasing aspirin (NCX-4016), interacts with selective COX-2 inhibitors to aggravate gastric damage and inflammation.

Aceylation of cyclooxygenase (COX)-2 by aspirin can trigger the formation of 15(R)-epilipoxin A4, or aspirin-triggered lipoxin (ATL). ATL exerts protective effects in the stomach. Selective COX-2 inhibitors block ATL synthesis and exacerbate aspirin-induced gastric damage. Nitric oxide-releasing aspirins, including NCX-4016, have antiplatelet effects similar to aspirin but do not cause gastric damage. In the present study, we examined whether or not NCX-4016 triggers ATL synthesis and/or upregulates gastric COX-2 expression and the effects of coadministration of NCX-4016 with a selective COX-2 inhibitor on gastric mucosal injury and inflammation. Rats were given aspirin or NCX-4016 orally and either vehicle or a selective COX-2 inhibitor (celecoxib) intraperitoneally. Gastric damage was blindly scored, and granulocyte infiltration into gastric tissue was monitored through measurement of myeloperoxidase activity. Gastric PG and ATL synthesis was measured as was COX-2 expression. Whereas celecoxib inhibited gastric ATL synthesis and increased the severity of aspirin-induced gastric damage and inflammation, coadministration of celecoxib and NCX-4016 did not result in damage or inflammation. NCX-4016 did not upregulate gastric COX-2 expression nor did it trigger ATL synthesis (in contrast to aspirin). Daily administration of aspirin for 5 days resulted in significantly less gastric damage than that seen with a single dose, as well as augmented ATL synthesis. Celecoxib reversed this effect. In contrast, repeated administration of NCX-4016 failed to cause gastric damage, whether given alone or with celecoxib. These studies support the notion that NCX-4016 may be an attractive alternative to aspirin for indications such as cardioprotection, including in individuals also taking selective COX-2 inhibitors.

Animals↗
PubMed1991

Urinary leukotriene E4 concentrations increase after aspirin challenge in aspirin-sensitive asthmatic subjects.

Urinary leukotriene E4 (LTE4) concentrations have been measured in six asthmatic patients with aspirin sensitivity and in five asthmatic subjects tolerant of aspirin, before and after provocation with aspirin or placebo. Aspirin-sensitive subjects showed an average 21% fall in FEV1 after aspirin challenge whereas control individuals had a 2% fall in FEV1 after ingestion of 100 mg aspirin. The resting urinary LTE4 concentrations in asthmatic subjects sensitive to aspirin were 243 pg/mg creatinine (range 50 to 1,041), and these were on average sixfold greater than those in control asthmatic subjects. Further, there was a mean fourfold increase in urinary LTE4 levels at 3 to 6 h after aspirin, but not placebo, challenge in aspirin-sensitive asthmatic subjects that was not seen in the control asthmatic individuals. Leukotriene release may play a central role in the mechanisms of asthmatic attacks produced by aspirin ingestion.

Adult↗
PubMed1983

Studies on aspirin derivatives with very little side effect. IV. Inhibitory effect of aspirin-isopropylantipyrine (AIA) on several experimental thromboses.

The effect of a new aspirin derivative, aspirin-isopropylantipyrine (AIA), with potent platelet anti-aggregant activity, on several experimental thromboses was evaluated and compared with that of aspirin. AIA (50 mg/kg, s.c.) as well as aspirin (50 mg/kg, s.c.) significantly inhibited thrombus formation in extracorporeal shunt model of rats. AIA (50 mg/kg, s.c.) significantly shortened the duration of apnea and respiratory distress induced by a rapid injection of adenosine 5'-diphosphate in rats, while aspirin (50 mg/kg, s.c.) did not. Inhibitory effect of AIA (50 mg/kg, s.c.) on arachidonic acid-induced mortality in mice was less than that of aspirin (50 mg/kg, s.c.). AIA and aspirin (10 mg/kg/d X 10, s.c.) had no effect on laurate-induced arterial occlusive disease in rats. AIA (200 microM) showed weak and reversible inhibition of prostaglandin I2 generation in isolated rat aorta strip, while aspirin (200 microM) showed irreversible inhibition. AIA (50 and 200 microM inhibited Ca2+-, K+- or norepinephrine-induced contraction on isolated rat aorta strip. AIA (200 microM) had no effect on malondialdehyde formation, cyclic AMP level and adenylate cyclase activity in rat platelets. AIA (100 microM) inhibited arachidonic acid-induced contraction on rat fundus strip by about 50%, while aspirin (100 microM) did not. These results strongly suggest that anti-thrombotic activity of AIA was originated at least from its anti-aggregant effect on platelets, differing from aspirin.

Adenosine Diphosphate↗
PubMed2006

The role of aspirin versus aspirin and heparin in cases of recurrent abortions with raised anticardiolipin antibodies.

BACKGROUND: The present study was undertaken to compare the role of aspirin versus aspirin plus heparin combination in pregnant women with poor obstetric history and raised anticardiolipin antibodies IgG (IgG(acl)). MATERIAL/METHODS: The study was conducted on 550 pregnant women, 450 with a history of two or more spontaneous abortions forming the study group, while 100 women with one or more live births and no history of abortion were controls. Their blood was tested to assess the level of IgG(acl) by enzyme-linked immunosorbent assay (ELISA). The test was strongly positive in 72 (16%) patients of the study group, who were randomized to receive either low-dose aspirin (80 mg/day) or a combination of low-dose aspirin (80 mg/day) and 5000 IU of unfractionated heparin subcutaneously 12 hourly under hospital surveillance. The pregnancy outcomes were statistically compared. RESULTS: Of the 39 patients treated with low-dose aspirin, 24 (61.5%) gave birth to live issues compared with 28 (84.8%) of the 33 women given a combination of aspirin and heparin (p<0.05), an overall success rate of 72.2%. Mean birth weight of the babies given treatment with heparin and aspirin was 3.21+/-0.33 kg compared with 2.77+/-0.14 kg achieved with aspirin alone (p<0.001). Both treatments were well tolerated. CONCLUSIONS: The study provides evidence that in cases of recurrent abortions with raised IgG(acl), treatment with a combination of aspirin and heparin showed better outcome than treatment with aspirin alone.

Abortion, Habitual↗
PubMed1985

Effects of aspirin and an aspirin-acetaminophen combination on the gastric mucosa in normal subjects. A double-blind endoscopic study.

Coadministration or preadministration of acetaminophen with aspirin affords partial protection against aspirin-induced gastric mucosal injury in animals. Recently, it was reported that preadministration of acetaminophen in humans yielded similar protection. That study used pylorus occlusion, intravenous atropine, and exogenous acid, and thus may not have mimicked the usual clinical situation. We studied a clinical regimen, in 7 normal volunteers. We coadministered acetaminophen (1.95 or 2.6 g/day) and aspirin (in a 1:1 ratio) and used gastroscopy to evaluate if there was gastric mucosal protection. Aspirin alone was used as a positive control. We found the expected significant increase in mucosal damage associated with increasing aspirin dose (p less than 0.05) comparing the lowest and highest aspirin doses (1.95 g vs. 3.9 g) after 7 days of continuous therapy. There was no difference in the degree of mucosal injury when receiving the same dose of aspirin (p = 0.38) whether or not acetaminophen was administered in a dose equal to that of aspirin. Thus, in a more normal clinical situation, we were unable to confirm the findings from the pylorus-occluded model, i.e., we failed to identify either a beneficial effect, or a trend, for protection from gross mucosal damage by the coadministration of acetaminophen and aspirin in equal dosages.

Acetaminophen↗
PubMed1988

Great variation in the response of tissue plasminogen activator activity, plasminogen activator inhibition and plasmin inhibition to endotoxin, aspirin and endotoxin after administration of aspirin.

The effect of endotoxin, aspirin and endotoxin after administration of aspirin on the tissue plasminogen activator activity (PAA), plasminogen activator inhibition (PAI) and plasmin inhibition (PI) was studied in the rat. PAA, PAI and PI were determined in key organs (brain, heart, lungs, kidneys, liver and aorta) spectrophotometrically by procedures involving hydrolysis of the chromogenic substrate S-2251. Aspirin at three different doses had not any significant effect on tissue PAA; PAI and PI were affected in several organs. Four hours after a sustained infusion of endotoxin PAA was found to be increased in brain, kidneys and aorta, decreased in heart and lungs, while in liver the PAA was unchanged compared to controls. Changes in PAI and PI showed also a tissue variation. In endotoxin-infused rats pretreated with aspirin the PAA changes induced by endotoxin were prevented or modified; PAI and PI were affected in most organs studied. However, this effect of aspirin was varying and depending on the tissue, the parameter studied and the dose of aspirin. In some organs, as the heart and lungs, changes in PAI or PI were noticed, while neither aspirin nor endotoxin separately induced such changes in these organs. Also, a differential response of PAI and PI to the same stimulus in the same tissue was a noteworthy finding. The results of the present study show that the response of PAA, PAI and PI to aspirin depends on the tissue, the physiological or pathophysiological condition of the tissue and the dose of the aspirin.

Animals↗
PubMed1993

High dose intravenous aspirin, not low dose intravenous or oral aspirin, inhibits thrombus formation and stabilizes blood flow in experimental coronary vascular injury.

OBJECTIVES: The purpose of this study was to assess the anti-thrombotic potential of various forms of aspirin administration. BACKGROUND: Platelet activation in response to endothelial injury has been implicated in acute coronary syndromes. METHODS: Delivering 100-microA anodal direct current to the intima of the left circumflex coronary artery in dogs at a site of moderate external stenosis provides a thrombogenic model of vascular injury. Animals were treated with aspirin (Group I, 20 mg/kg intravenously [n = 11]; Group II, 4.6 mg/kg intravenously [n = 6]; Group III, 4.6 mg/kg orally 18 h before the experiment [n = 7]) or vehicle (Group IV, control [n = 11]). RESULTS: The time required for thrombotic occlusion to occur was longer and the incidence of thrombosis was lower in Group I (Group I, 238 +/- 7 min [n = 2]; Group II, 127 +/- 25 min [n = 3]; Group III, 156 +/- 35 min [n = 6]; Group IV, 90 +/- 11 min [n = 11]) (p < 0.05). Thrombus mass was smaller in Group I (Group I, 5.0 +/- 0.8 mg; Group II, 12.2 +/- 2.6 mg; Group III, 11.6 +/- 3.9 mg; Group IV, 9.1 +/- 1.6 mg) (p < 0.05). Initial hemodynamic variables did not differ among groups. An increase in mean arterial pressure was noted for several hours after intravenous aspirin administration in Group I (99 +/- 5 to 110 +/- 4 mm Hg) (p < 0.05). Left circumflex coronary artery blood flow was stable for 5 h in Group I (Group I, 31 +/- 2 to 26 +/- 4 ml/min) but decreased in all the other groups (Group II, 26 +/- 4 to 10 +/- 5 ml/min; Group III, 27 +/- 5 to 7 +/- 7 ml/min; Group IV, 29 +/- 4 to 0 ml/min) (p < or = 0.05). The in vivo area of left ventricle perfused by the left circumflex coronary artery was not different among groups. Platelet counts were similar and did not change over the course of the protocol. Ex vivo arachidonic acid-induced platelet aggregation decreased in all groups after aspirin (p < or = 0.001). Indium-111-labeled platelet adherence to the coronary vasculature was decreased in distal vessel segments after all doses of aspirin (p < 0.05). Platelet deposition in thrombi was similar for all treatment groups. CONCLUSIONS: High dose intravenous aspirin has salutary effects. It stabilizes left circumflex coronary artery blood flow, prolongs the time to thrombosis, reduces the incidence of thrombotic occlusion, reduces thrombus mass and limits platelet adherence to sites of arterial injury. Low dose aspirin given intravenously or orally was ineffective. When persistent intracoronary thrombi precipitate unstable coronary syndromes, high dose intravenous aspirin may be useful in the acute period even though platelets continue to interact with injured vascular segments through aspirin-insensitive mechanisms.

Administration, Oral↗
PubMed1999

Comparison of the efficacy and safety of aspirin alone with coumadin plus aspirin after provisional coronary stenting: final and follow-up results of a randomized study.

BACKGROUND: The antithrombotic benefit of the conventional treatment with coumadin after coronary stenting is limited by bleeding complications. However, the superiority of an antiplatelet therapy with aspirin alone compared with coumadin plus aspirin has not been proven by randomized studies. The efficacy and safety of treatment with aspirin alone in comparison to coumadin plus aspirin were evaluated in this randomized study. METHODS: Out of 164 patients aged 59.7 +/- 9.2 years, 79 patients were randomly assigned to receive 100 mg aspirin daily (group A) and 85 patients randomly assigned to coumadin plus aspirin (group CA) after provisional coronary stenting with a high-pressure technique. The primary end point was defined as the absence of death, subacute closure of the target vessel, myocardial infarction, urgent coronary bypass surgery, repeated coronary angioplasty, and peripheral vascular complications requiring transfusion or surgery. High-pressure inflation technique was used, but ultrasound guidance was not. RESULTS: During hospitalization (median 8 days), 135 patients (82. 3%) were free of events (A, 84.8%; CA, 80.8%; P =.42). Eleven (6.7%) subacute closures occurred (A, 10.1%; CA, 3.5%; P =.09); 2 of them were lethal in the aspirin group. Emergency bypass surgery was performed in 1 patient in each group. Peripheral vascular complications were observed in 13 patients (7.9%) (A, 1.3%; CA, 14. 1%; P <.01). At 3-month follow-up, 15 (9.1%) elective revascularization procedures (A, 7.6%; CA, 10.6%; P =.51) were performed. CONCLUSION: Aspirin alone at the low dose of 100 mg administered or the combination of coumadin and aspirin after high-pressure coronary stenting does not prevent adverse clinical events when ultrasound guidance is not used.

Angioplasty, Balloon, Coronary↗