Prostaglandins and Platelet Aggregation in Vivo

1970 ◽  
Vol 23 (02) ◽  
pp. 286-292 ◽  
Author(s):  
J Kloeze
Keyword(s):  
Platelet Aggregation ◽  
Intravenous Injection ◽  
Adenosine Diphosphate ◽  
Causative Factor ◽  
Respiratory Arrest ◽  
Platelet Thrombi ◽  
Eventual Death ◽  
The Brain

SummaryProstaglandins E1 and ω-homo-E1 which were shown previously to inhibit adenosine diphosphate (ADP)-induced platelet aggregation in vitro have now been found to inhibit this process also in vivo. Both prostaglandins inhibit transient thrombocytopenia induced by intravenous injection of ADP; PGE1 increases also the LD 50 of ADP when injected in high amounts into young rats. In both cases platelet aggregation in vivo is the primary cause of the phenomena observed.The symptoms observed on overdosing ADP by intravenous injection are unconsciousness within 10-20 sec after completion of the injection immediately followed by respiratory arrest and eventual death of the animal, generally within 10 min. It seems that blocking of the supply of blood to the brain by platelet thrombi, which on histological examination were found to occlude blood vessels in different organs, is the most important causative factor of the symptoms observed.

Prostaglandins and Platelet Aggregation in Vivo

1970 ◽  
Vol 23 (02) ◽  
pp. 293-298 ◽  
Author(s):  
J Kloeze
Keyword(s):  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Primary Role ◽  
Electric Stimulus ◽  
Platelet Thrombi

SummaryIt was shown previously that prostaglandin E1 (PGE1) inhibits the aggregation of blood platelets in vitro whereas PGF1α does not; in vivo, PGE1 inhibits in rats the action of intravenously injected adenosine diphosphate. Locally administered PGE1 is found in the present experiment to inhibit in rats the formation and growth of platelet thrombi, induced by an electric stimulus in cortical veins. PGF1α appeared to be inactive.The morphology of platelet thrombi induced by an electric stimulus is shown. The probability of a primary role of erythrocytes in the formation of this type of thrombi is discussed.

scholarly journals "Impotent" Platelets in Albinos With Prolonged Bleeding Times

Blood ◽  
1972 ◽  
Vol 39 (4) ◽  
pp. 490-499 ◽  
Author(s):  
Harold M. Maurer ◽  
James A. Wolff ◽  
Sue Buckingham ◽  
Arthur R. Spielvogel
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Bleeding Tendency ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time ◽  
Normal Platelet ◽  
Tryptophan Metabolites ◽  
History Of

Abstract Functional, biochemical, and morphologic platelet abnormalities are reported in four children with the syndrome of albinism, mild bleeding tendency, prolonged bleeding time, and normal platelet count. In these children, primary platelet aggregation with adenosine diphosphate occurred normally, but secondary aggregation was impaired. Collagen and norepinephrine produced almost no platelet aggregation. Platelet content of serotonin (5-HT) was markedly reduced, and uptake and retention of 5-HT by the platelets in vivo and in vitro was poor. In one child who was given a tryptophan load, urinary tryptophan metabolites were normal, suggesting that there was no evidence of a block in the 5-HT synthetic pathway in the gastrointestinal tract. Electron microscopy revealed an absence of densely osmophilic granules in 5-HT poor platelets. Platelets from other albinos with no history of bleeding contained normal amounts of 5-HT and densely osmophilic granules.

The Potentiation of Platelet Aggregation and Adhesion by Heparin in Vitro and in Vivo

1973 ◽  
Vol 45 (4) ◽  
pp. 485-494 ◽  
Author(s):  
C. Thomson ◽  
C. D. Forbes ◽  
C. R. M. Prentice
Keyword(s):  
Platelet Aggregation ◽  
Intravenous Injection ◽  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Test Cell ◽  
Release Reaction ◽  
Platelet Release ◽  
Increase Platelet Aggregation

1. Heparin has been shown to increase platelet aggregation by ADP and adrenaline and to enhance the platelet release reaction when tested in citrated platelet-rich plasma (P.R.P.). This activity is present when heparin is added to P.R.P. or when P.R.P. is prepared after intravenous injection of heparin, and when heparin is added to non-anticoagulated native P.R.P. 2. Retention of platelets by cellophane membranes within a specially designed test-cell was significantly increased when heparin was added to citrated whole blood. 3. Though aspirin blocks the release reaction with and without heparin, it does not prevent the potentiation of initial ADP or first wave adrenaline aggregation caused by heparin.

scholarly journals Effect of propranolol on platelet function

Blood ◽  
1977 ◽  
Vol 49 (2) ◽  
pp. 185-196 ◽  
Author(s):  
BB Weksler ◽  
M Gillick ◽  
J Pink
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Direct Action ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Ionophore A23187 ◽  
Atherosclerotic Vascular Disease ◽  
Clot Retraction

Abstract Excessive reactivity of blood platelets may contribute to atherosclerotic vascular disease. Hence drugs which alter platelet function may be protective. Prompted by findings that propranolol therapy normalized hyperactive platelet aggregation in patients with coronary artery disease, we studied propranolol in vitro to assess its action on platelets. At concentrations similar to those achieved in vivo (0.1–1 muM), propranolol raised the thresholds for aggregation of some normal paltelets by adenosine diphosphate (ADP). At higher concentrations (10-50 muM), propranolol abolished the second wave of platelet aggregation induced by ADP and epinephrine, and inhibited aggregation induced by collagen, thrombin, and the ionophore A23187. Propanolol blocked the release of 14C-serotonin from platelets, inhibited platelet adhesion to collagen, and interfered with clot retraction. Propranolol blocked ionophore-induced uptake of 45Ca by platelets. Inhibition appeared unrelated to beta-adrenergic blockage, as d(+) propranolol (which lacks beta-blocking activity) was equipotent with 1(-) propranolol. Moreover, practolol, a beta-blockading drug which is nonlipophilic, did not inhibit platelet function. These studies suggested that propranolol, like local anesthetics, decreased platelet responsiveness by a direct action on the platelet membrane, possibly by interfering with calcium availability. Modulation of platelet function by propranolol may occur at concentrations achieved at usual clinical doses of the drug.

A Comparative Study of Platelet Aggregation in Man and Laboratory Animals

1970 ◽  
Vol 24 (03/04) ◽  
pp. 385-394 ◽  
Author(s):  
D. C Macmillan ◽  
A. K SIM
Keyword(s):  
Clinical Trials ◽  
Platelet Aggregation ◽  
Comparative Study ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Thromboembolic Disease ◽  
Considerable Importance ◽  
Laboratory Animals ◽  
Platelet Thrombi

SummaryWhen some human platelets were aggregated in vitro by exogenous adenosine diphosphate (ADP) or adrenaline they released their own ADP. As ADP is the final stimulator of most aggregation, this ability to produce its own release gave a self- propagating secondary aggregation (SA) which could be marked in certain individuals and diseased states. In a survey of several animals, this ability to produce self- propagating aggregation was also found in a marked form in cats (which can form systemic platelet thrombo-emboli) and to a less extent in baboons and some dogs. This property of the platelets of humans and cats could be an important factor in their ability to form platelet thrombi more easily than other mammals. Thus, SA and its inhibition by drugs may be of considerable importance in the management of thromboembolic disease and a study of such agents carried out in these animals may be reasonably regarded as a relevant and useful preliminary to clinical trials in man.

Human Platelet Aggregation In Response To Multiple Agonists In Plasma Anticoagulated With Heparin

1981 ◽  
Author(s):  
H A Culliver ◽  
N G Ardlie
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Human Platelet Aggregation

The lowest concentrations at which epinephrine and vasopressin have been reported to interact positively in causing platelet aggregation in vitro are at least two orders of magnitude greater than the physiological concentrations of these hormones in blood. The aim of this study was to examine the interaction between several agonists of human platelet aggregation. The aggregating agents used were adenosine diphosphate (ADP), epinephrine, norepinephrine, 5-hydroxytryptamine and vasopressin. Platelet-rich plasma (PRP) was prepared from blood anticoagulated with minimal concentrations of heparin in an attempt to more closely reflect the in vivo situation.Aggregation caused by ADP was potentiated by epinephrine at a concentration exceeding the level obtained in circulating blood. When a third agonist (vasopressin) was used in combination with ADP and epinephrine, aggregation was enhanced at concentrations of vasopressin and epinephrine obtained in blood. When used as a fourth agonist norepinephrine and 5-hydroxytryptamine potentiated aggregation at physiological concentrations. The response to multiple agonists was greater in heparinized PRP than citrated PRP. Hirudin decreased the extent of aggregation in heparinized PRP caused by multiple agonists suggesting that thrombin may be involved.Since the concentrations of combined agonists required to induce in vitro platelet aggregation can be obtained in circulating blood these findings may explain why platelet activation occurs in certain pathological states.

scholarly journals Involvement of platelet-derived VWF in metastatic growth of melanoma in the brain

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Jose R Robador ◽  
Manuel J Feinauer ◽  
Stefan W Schneider ◽  
Frank T Mayer ◽  
Christian Gorzelanny ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Fiber Formation ◽  
Brain Targeting ◽  
Induce Platelet Aggregation ◽  
Promising Therapeutic Approach ◽  
Metastatic Growth ◽  
The Brain

Abstract Background The prognosis of patients with brain metastases (BM) is poor despite advances in our understanding of the underlying pathophysiology. The high incidence of thrombotic complications defines tumor progression and the high mortality rate. We, therefore, postulated that von Willebrand factor (VWF) promotes BM via its ability to induce platelet aggregation and thrombosis. Methods We measured the abundance of VWF in the blood and intravascular platelet aggregates of patients with BM, and determined the specific contribution of endothelial and platelet-derived VWF using in vitro models and microfluidics. The relevance for the brain metastatic cascade in vivo was demonstrated in ret transgenic mice, which spontaneously develop BM, and by the intracardiac injection of melanoma cells. Results Higher levels of plasma VWF in patients with BM were associated with enhanced intraluminal VWF fiber formation and platelet aggregation in the metastatic tissue and peritumoral regions. Platelet activation triggered the formation of VWF multimers, promoting platelet aggregation and activation, in turn enhancing tumor invasiveness. The absence of VWF in platelets, or the blocking of platelet activation, abolished platelet aggregation, and reduced tumor cell transmigration. Anticoagulation and platelet inhibition consistently reduced the number of BM in preclinical animal models. Conclusions Our data indicate that platelet-derived VWF is involved in cerebral clot formation and in metastatic growth of melanoma in the brain. Targeting platelet activation with low-molecular-weight heparins represents a promising therapeutic approach to prevent melanoma BM.

scholarly journals Functionalised LRP1 targeted carbon nanotubes across the blood-brain barrier in vitro and in vivo after intravenous injection

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv3-iv3
Author(s):  
Julie Wang ◽  
Houmam Kafa ◽  
Noelia Rubio ◽  
Sukhvinder Bansal ◽  
Frederic Festy ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Blood Brain Barrier ◽  
Intravenous Injection ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Blood Brain ◽  
The Brain

Abstract Despite extensive research in drug development, brain cancer is still lacking an efficacious cure due to the inability to deliver current therapeutics to the brain across the blood-brain barrier (BBB). Chemically functionalized carbon nanotubes (f-CNT) constitute a novel class of nanomaterials with attractive physical, chemical and electronic properties. The key advantage of f-CNTs is the extremely high surface area to size ratio allowing a high degree of chemical functionalization making them invaluable tools for designing drug delivery systems to the brain. One of the most interesting characteristics of f-CNTs is their ability to translocate across plasma membranes and enter the cells either passively by direct translocation across membranes or actively via endocytosis. Herein, we confirmed the ability of f-CNTs to cross the BBB and reach the brain in in vitro using a co-culture model of PBEC and primary rat astrocytes and in vivo after intravenous injection. Thanks to their unique optical properties, the uptake of f-CNT in brain was confirmed using state-of-the-art spectroscopic imaging techniques such as multi-photon luminescence imaging, fluorescence lifetime microscopy and Raman spectroscopy. Conjugation with angiopep-2 (ANG), a small peptide targeting the LRP1 receptor overexpressed in the BBB and glioma cells, further enhanced brain parenchyma accumulation in healthy brains. Higher uptake in glioma than brain parenchyma was also observed in glioma-bearing mice after intravenous administration. The inherent brain accumulation ability of f-CNTs coupled with improved brain-targeting by ANG favours the future clinical applications of f-CNTs-ANG to deliver active therapeutics for brain glioma therapy.

Piretanide: A New Synthetic Fibrinolytic and Anti-Platelet Agent

1986 ◽  
Vol 56 (03) ◽  
pp. 360-363 ◽  
Author(s):  
I S Chohan
Keyword(s):  
Single Dose ◽  
Platelet Aggregation ◽  
Fibrinolytic Activity ◽  
Adenosine Diphosphate ◽  
Platelet Factor ◽  
Anti Platelet Agent ◽  
Effective Inhibition ◽  
Primary Platelet

SummaryPiretanide, 4-phenoxy-3-(l-pyrrolidinyl)-5-sulfamoyl benzoic acid, a potent diuretic, enhances endogenous plasma fibrinolytic activity after a single dose of 6 mg administered orally. Acceleration of fibrinolytic activity becomes manifest within 1 h, reaches its peak in 3 h and is associated with little change in fibrinogen, however, it is accompanied with diminished urokinase excretion initially. Piretanide does not cause lysis of fibrin in vitro in any concentration. Primary platelet aggregation, induced by adenosine-diphosphate, is inhibited by piretanide, in vivo. In in vitro experiments piretanide leads to effective inhibition of ADP-induced platelet aggregation with complete inhibition at 5 mM concentration. Piretanide, after ingestion of a single dose of 6 mg, causes highly significant decrease of platelet factor-4 release.

scholarly journals Effect of propranolol on platelet function

Blood ◽  
1977 ◽  
Vol 49 (2) ◽  
pp. 185-196
Author(s):  
BB Weksler ◽  
M Gillick ◽  
J Pink
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Direct Action ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Ionophore A23187 ◽  
Atherosclerotic Vascular Disease ◽  
Clot Retraction

Excessive reactivity of blood platelets may contribute to atherosclerotic vascular disease. Hence drugs which alter platelet function may be protective. Prompted by findings that propranolol therapy normalized hyperactive platelet aggregation in patients with coronary artery disease, we studied propranolol in vitro to assess its action on platelets. At concentrations similar to those achieved in vivo (0.1–1 muM), propranolol raised the thresholds for aggregation of some normal paltelets by adenosine diphosphate (ADP). At higher concentrations (10-50 muM), propranolol abolished the second wave of platelet aggregation induced by ADP and epinephrine, and inhibited aggregation induced by collagen, thrombin, and the ionophore A23187. Propanolol blocked the release of 14C-serotonin from platelets, inhibited platelet adhesion to collagen, and interfered with clot retraction. Propranolol blocked ionophore-induced uptake of 45Ca by platelets. Inhibition appeared unrelated to beta-adrenergic blockage, as d(+) propranolol (which lacks beta-blocking activity) was equipotent with 1(-) propranolol. Moreover, practolol, a beta-blockading drug which is nonlipophilic, did not inhibit platelet function. These studies suggested that propranolol, like local anesthetics, decreased platelet responsiveness by a direct action on the platelet membrane, possibly by interfering with calcium availability. Modulation of platelet function by propranolol may occur at concentrations achieved at usual clinical doses of the drug.

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