Assessment of Antithrombotic Properties of Sodium Ibuprofen

1982 ◽  
Vol 48 (01) ◽  
pp. 087-090 ◽  
Author(s):  
Carlos O Esquivel ◽  
David Bergqvist ◽  
Claes-Göran Björck ◽  
Stan N Carson ◽  
Bodil Nilsson
Keyword(s):  
Drug Administration ◽  
Platelet Function ◽  
Ex Vivo ◽  
Inhibitory Effect ◽  
Formation Time ◽  
Platelet Activity ◽  
Laser Injury ◽  
Sodium Ibuprofen ◽  
Plug Formation

SummaryThe effect of sodium ibuprofen on platelet activity in vivo and the lysability of ex vivo thrombi was investigated. The formation of a hemostatic platelet plug in the rabbit mesentery and platelet embolism as a response to a laser-induced injury in the ear chamber of rabbits were used as models for determining platelet activity. Ibuprofen at a dose of 25 mg/kg i.v. was found to increase the primary (PHT) and the total hemostatic plug formation time (THT). The same dose decreased the number of cumulative emboli over a 10 min period after a laser injury to arterioles. A dose of 10 mg/kg i.v. did not affect the formation of the hemostatic platelet plug. In dogs, doses of 10, 25 und 50 mg/kg did not enhance the release of 125I-FDP from the thrombi after incubation in plasmin, but the largest dose which is approximately five times the recommended dose in humans, did significantly decrease the thrombus weight 90 and 180 min after the drug administration. In conclusion, sodium ibuprofen was shown to have an inhibitory effect on platelet function in vivo and in large doses was also found to diminish the thrombus weight.

Microvascular Haemostasis and the Effect of Local Stimulation and inhibition of Platelet Function. An Experimental Study in Rabbits

1976 ◽  
Vol 36 (01) ◽  
pp. 133-139 ◽  
Author(s):  
D Bergqvist ◽  
K.-E Arfors
Keyword(s):  
Experimental Study ◽  
Platelet Function ◽  
Prostaglandin E1 ◽  
Red Cells ◽  
Formation Time ◽  
Laser Injury ◽  
Potent Stimulator ◽  
Plug Formation ◽  
Local Stimulation ◽  
Mesenteric Microcirculation

SummaryThe local stimulation and inhibition of haemostatic plug formation was studied by local infusion and superfusion of different agents – ADP, thrombin, adenosine, heparin, prostaglandin E1 (PGE1) and laser injury. ADP and laser injury shortened venular haemostatic plug formation time whereas adenosine in the superfusate and PGE1 prolonged it. Thrombin infusion had no effect but thrombin in the superfusate significantly stabilised the haemostatic plugs. It is suggested that ADP released from red cells is the most potent stimulator for haemostatic plug formation in the rabbit mesenteric microcirculation.

The Effect of Serotonin Inhibition on Initial Microvessel Hemostasis and Platelet Aggregation In Vivo

1983 ◽  
Vol 49 (03) ◽  
pp. 173-175 ◽  
Author(s):  
D Bergqvist ◽  
S Arvidsson ◽  
C O Esquivel ◽  
B Lindblad ◽  
U Haglund
Keyword(s):  
Adrenergic Receptor ◽  
Formation Time ◽  
Platelet Activity ◽  
Receptor Affinity ◽  
Rabbit Ear ◽  
Rabbit Ear Chamber ◽  
Plug Formation ◽  
Mesenteric Microcirculation

SummaryThe role of serotonin (5-HT) in initial microvascular hemostasis is not fully understood. This study was made to evaluate the effect on hemostatic plug formation and laser-induced arteriolar microembolism of different substances which counteract the effect of 5-HT. Hemostatic plug formation time and stability was measured in the rabbit mesenteric microcirculation and laserinduced embolism in the rabbit ear chamber. Ketanserine, a selective 5-HT2-receptor blocker shortened arteriolar hemostatic plug formation time. Dihydroergotamine, an unselective blocker (with 5-HT- and α-adrenergic receptor affinity) increased venular hemostatic plug formation time and also decreased the hemostatic plug stability. Laser-induced platelet embolism was unaltered after both ketanserine and dihydroergotamine administration. The magnitude of these changes seems to exclude an important effect of 5-HT in initial microvessel hemostasis or on platelet activity.

Platelet Activity In Vivo in Hyperlipoproteinemia – Importance of Combined Hyperlipidemia

1998 ◽  
Vol 79 (02) ◽  
pp. 268-275 ◽  
Author(s):  
Anders Bröijersén ◽  
Anders Hamsten ◽  
Mats Eriksson ◽  
Bo Angelin ◽  
Paul Hjemdahl
Keyword(s):  
Urinary Excretion ◽  
Platelet Function ◽  
Mental Stress ◽  
Ex Vivo ◽  
Platelet Activity ◽  
Leukocyte Counts ◽  
Artery Disease ◽  
Platelet Secretion

SummaryPlatelet hyperactivity in vitro is found in patients with isolated hypercholesterolemia. It is, however, less well established if platelet activity in vivo is enhanced, and if there are differences between various types of hyperlipoproteinemia.Platelet function in vivo was studied at rest and during mental stress in men with isolated hypercholesterolemia (phenotype IIa; n = 21) or combined hyperlipidemia (phenotype IIb; n = 29), and age-matched normolipidemic controls (n = 41). The urinary excretion of 11-dehydrothromboxane B2 was elevated in patients compared to controls (IIa, p <0.05; IIb, p <0.001), and higher in type IIb than in IIa patients (p <0.05). Platelet secretion, assessed as plasma β-thromboglobulin levels, was higher in type IIb patients compared to controls (p <0.01) and type IIa patients (p <0.05) during mental stress. The urinary excretion of β-thromboglobulin was also elevated in type IIb patients compared to controls (p <0.05). Platelet aggregability at rest, as measured by filtragometry ex vivo was, however, reduced in both patient groups compared to controls (p <0.05). No correlations were found between plasma lipoprotein levels and markers of platelet function in vivo. Type IIb patients had higher plasma fibrinogen levels and higher leukocyte counts than controls (p <0.05 and p <0.001) and type IIa patients (p <0.05 and p = 0.06). Thromboxane excretion was positively related to fibrinogen levels and leukocyte counts (p <0.01 for both). Preliminary data regarding serum TNF-α also indicated an elevation of this inflammatory cytokine in type IIb patients (p <0.05 vs controls).In conclusion, thromboxane generation and platelet secretion in vivo are enhanced in patients with hypercholesterolemia, and particularly so among patients with concomitant elevation of plasma triglycerides. The mechanism is unknown, but inflammatory mediators may be involved. The present findings are of interest in relation to the role of triglycerides in coronary artery disease.

Measurement of the Platelet Response to Laser- induced Microvascular Injury

1974 ◽  
Vol 32 (02/03) ◽  
pp. 704-713 ◽  
Author(s):  
F. N McKenzie ◽  
K.-E Arfors ◽  
N. A Matheson
Keyword(s):  
Inhibitory Effect ◽  
Microvascular Blood Flow ◽  
Platelet Response ◽  
High Concentration ◽  
Platelet Activity ◽  
Microvascular Injury ◽  
Arterial Blood ◽  
Proximal Site ◽  
Adenosine Phosphates

SummaryA study has been made of the biochemical factors underlying the platelet response to laser-induced microvascular injury. A platelet aggregating substance is produced at sites of laser-induced injury which markedly stimulates platelet activity at a site of injury inflicted a short distance downstream. Distal sites of injury are not similarly influenced if the distance between the injuries is increased or if the proximal site no longer shows platelet-stimulating activity. The stimulating effect of an adjacent proximal injury on platelet activity at a distal site is inhibited by local intra-arterial infusion of adenosine. Measurements of arterial blood pressure and microvascular blood flow velocity during adenosine infusion showed that its inhibitory effect on platelet activity is largely independent of its vasodilator properties. The effect of infusion of different adenosine phosphates (AMP, ADP, ATP) was also studied. Very small amounts of ADP markedly stimulated platelet activity and the emboli formed were similar to those normally produced at sites of laser injury. At high concentration AMP inhibited while ATP stimulated platelet activity in vivo. The results emphasise the fundamental role of ADP as a mediator of the platelet response at sites of laser- induced microvascular injury.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

scholarly journals ROLE OF NITRIC OXIDE (NO) IN CAPSAICIN MEDIATED ANTI-PLATELET ACTIVITY IN IN VITRO, IN VIVO, EX-VIVO MODEL OF PLATELET AGGREGATION ASSAY AND ARTERIAL THROMBOSIS IN RAT: POTENTIAL THERAPEUTIC TARGET?

2018 ◽  
Vol 10 (4) ◽  
pp. 44
Author(s):  
Mihir K Patel ◽  
Kiranj K. Chaudagar ◽  
Anita A. Mehta
Keyword(s):  
Platelet Aggregation ◽  
Arterial Thrombosis ◽  
Ex Vivo ◽  
Platelet Activity ◽  
Aggregation Assay ◽  
Thrombosis Model ◽  
Platelet Aggregation Assay

Objective: Although recent advances in the treatment of congestive heart disease, mortality among patients’ remains a questionable remark. Therefore, we evaluated the role of capsaicin on in vitro and ex vivo platelet aggregation induced by Adenosine Di-Phosphate (ADP) as well as in in vivo thrombosis models and role of NO, KATP was also identified in the capsaicin-induced anti-platelet animal model as well as in vivo model of arterial thrombosis.Methods: According to body weight wistar rats were divided into five groups. Group I and Group II was treated with saline and capsaicin (3 mg/kg, i. v), while animals from Group III were treated with N(ω)-nitro-L-arginine methyl ester (L-NAME) (30 mg/kg, i. v) 30 min before administration of capsaicin (3 mg/kg, i. v). Group IV animals were treated with glibenclamide (10 mg/kg,i. v) 30 min before administration of capsaicin (3 mg/kg, i. v). Group V was considered as a positive control and administered clopidogrel (30 mg/kg, p. o). Animals were subjected for in vitro, ex-vivo platelet aggregation assay. ADP (30µM) was utilized as an aggregating agent in these experiments. After these assays; animals of each group were subjected for subaqueous tail bleeding time in a rat model and FeCl3-induced arterial thrombosis model in rats.Results: In ADP-induced in vitro platelet aggregation, a significant reduction in % platelet aggregation was observed at 50µM (64.35±4.641) and 100µM (52.72±4.192) concentration of capsaicin as compared to vehicle control (85.82±3.716). Capsaicin (3 mg/kg, i. v) also showed a significant reduction (49.53±4.075) in ex-vivo ADP-induced platelet aggregation as compared to vehicle control (89.38±2.057). In FeCl3 induced arterial thrombosis model, Capsaicin (3 mg/kg, i. v) exhibited an increase in time to occlusion in this rodent model and presence of the L-NAME and glibenclamide had inhibited the activity of capsaicin.Conclusion: In our study, capsaicin (50 µM, 100µM) exhibited potent anti-platelet activity in ADP-induced platelet aggregation, similarly capsaicin exhibited significant anti-platelet action in the ex-vivo study. Moreover, the presence of L-NAME and glibenclamide inhibited the anti-thrombotic and anti-platelet action of capsaicin. Therefore, it was concluded that NO and KATP may be involved in the anti-thrombotic action of capsaicin.

Comparison of the effect of coagulation and platelet function impairments on various mouse bleeding models

2014 ◽  
Vol 112 (08) ◽  
pp. 412-418 ◽  
Author(s):  
Nima Vaezzadeh ◽  
Ran Ni ◽  
Paul Y. Kim ◽  
Jeffrey I. Weitz ◽  
Peter L. Gross
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Saphenous Vein ◽  
Ex Vivo ◽  
Arterial Injury ◽  
Inhibitory Antibody ◽  
Study Objective ◽  
Tail Tip

SummaryHaemostatic impairments are studied in vivo using one of several murine bleeding models. However it is not known whether these models are equally appropriate for assessing coagulation or platelet function defects. It was our study objective to assess the performance of arterial, venous and combined arterial and venous murine bleeding models towards impaired coagulation or platelet function. Unfractionated heparin (UFH) or αIIbβ3 inhibitory antibody (Leo.H4) were administered to mice, and their effects on bleeding in saphenous vein, artery, and tail tip transection models were quantified and correlated with their effects on plasma clotting and ADP-induced platelet aggregation, respectively. All models exhibited similar sensitivity with UFH (EC50 dose = 0.19, 0.13 and 0.07 U/g, respectively) (95% CI = 0.14 – 0.27, 0.08 – 0.20, and 0.03 – 0.16 U/g, respectively). Maximal inhibition of ex vivo plasma clotting could be achieved with UFH doses as low as 0.03 U/g. In contrast, the saphenous vein bleeding model was less sensitive to αIIbβ3 inhibition (EC50 = 6.9 µg/ml) than tail transection or saphenous artery bleeding models (EC50 = 0.12 and 0.37 µg/ml, respectively) (95% CI = 2.4 – 20, 0.05 – 0.33, and 0.06 – 2.2 µg/ml, respectively). The EC50 of Leo.H4 for ADP-induced platelet aggregation in vitro (8.0 µg/ml) was at least 20-fold higher than that of the tail and arterial, but not the venous bleeding model. In conclusion, venous, arterial and tail bleeding models are similarly affected by impaired coagulation, while platelet function defects have a greater influence in models incorporating arterial injury.

scholarly journals Human Immunodeficiency Virus Inhibits Multilineage Hematopoiesis In Vivo

1998 ◽  
Vol 72 (6) ◽  
pp. 5121-5127 ◽  
Author(s):  
Prasad S. Koka ◽  
John K. Fraser ◽  
Yvonne Bryson ◽  
Gregory C. Bristol ◽  
Grace M. Aldrovandi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Erythroid Differentiation ◽  
Inhibitory Effect ◽  
Immunodeficiency Virus ◽  
The Many ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-infected individuals often exhibit multiple hematopoietic abnormalities reaching far beyond loss of CD4+ lymphocytes. We used the SCID-hu (Thy/Liv) mouse (severe combined immunodeficient mouse transplanted with human fetal thymus and liver tissues), which provides an in vivo system whereby human pluripotent hematopoietic progenitor cells can be maintained and undergo T-lymphoid differentiation and wherein HIV-1 infection causes severe depletion of CD4-bearing human thymocytes. Herein we show that HIV-1 infection rapidly and severely decreases the ex vivo recovery of human progenitor cells capable of differentiation into both erythroid and myeloid lineages. However, the total CD34+ cell population is not depleted. Combination antiretroviral therapy administered well after loss of multilineage progenitor activity reverses this inhibitory effect, establishing a causal role of viral replication. Taken together, our results suggest that pluripotent stem cells are not killed by HIV-1; rather, a later stage important in both myeloid and erythroid differentiation is affected. In addition, a primary virus isolated from a patient exhibiting multiple hematopoietic abnormalities preferentially depleted myeloid and erythroid colony-forming activity rather than CD4-bearing thymocytes in this system. Thus, HIV-1 infection perturbs multiple hematopoietic lineages in vivo, which may explain the many hematopoietic defects found in infected patients.

5 Cold stored platelets correct cardiac surgery induced platelet dysfunction

2021 ◽  
Vol 167 (3) ◽  
pp. e1.5-e1
Author(s):  
Tom Scorer ◽  
Andrew Mumford
Keyword(s):  
Cardiac Surgery ◽  
Shelf Life ◽  
Platelet Function ◽  
Platelet Transfusion ◽  
Ex Vivo ◽  
Flow Chamber ◽  
Platelet Dysfunction ◽  
Current Standard ◽  
Blood Samples

IntroductionPlatelet dysfunction (thrombocytopathy) is a major problem in the bleeding patient and increases morbidity and healthcare costs. The thrombocytopathy resulting from cardiopulmonary bypass (CPB) can be used to study therapies targeted to improve outcomes in other scenarios, such as trauma. Platelet transfusion is used widely to correct thrombocytopathy. However, the current standard, room temperature stored platelets (RTP) have several disadvantages including; short shelf life, risk of bacterial contamination and deterioration in platelet function during storage. Cold stored platelets (CSP) are a potential alternative product with longer shelf life, reduced contamination risk and better-preserved platelet function.MethodsUsing ex vivo mixing studies, we investigated whether CSP were better able to reverse the thrombocytopathy associated with cardiac surgery than RTP. Blood samples were collected from 20 cardiac surgery patients. Donor platelets were split into two bags and stored at either 4°C (CSP), or 22°C (RTP) for up to seven days. The donor platelets were mixed with the patient blood samples to simulate platelet transfusion. The mixed samples were analysed using the TEG 5000 and using a collagen coated flow chamber at arterial shear. Patient samples were analysed alongside healthy controls (n = 20).ResultsAfter mixing the patient samples with CSP, the TEG R times were shorter than in samples mixed with RTP (p<0.0001), indicating more rapid initiation of clot formation. In the flow chamber experiments, the clot volume was greater in the patient samples mixed with CSP compared with samples mixed with RTP (p<0.0001).ConclusionsThese findings suggest that CSP, but not RTP can partially reverse the thrombocytopathy associated with cardiac surgery ex vivo, at clinically relevant mixing volumes. Reversal of thrombocytopathy by mixing CSP was greatest in the arterial shear model, which may indicate superior in vivo efficacy that requires confirmation in clinical trials.* this abstract presentation was awarded First Place.

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