Thiopental enhances human platelet aggregation by increasing arachidonic acid release

2001 ◽  
Vol 79 (10) ◽  
pp. 854-860 ◽  
Author(s):  
Rie Kitamura ◽  
Hideo Hirakata ◽  
Hiroto Okuda ◽  
Masami Sato ◽  
Hiroshi Toda ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Cytosolic Calcium ◽  
Free Calcium ◽  
Human Platelet Aggregation ◽  
Low Concentrations ◽  
Acid Release ◽  
Control Study

Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2 formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30–300 µM). Platelet activation was induced by adenosine diphosphate (ADP, 0.5–15 µM), epinephrine (0.1–20 µM) arachidonic acid (0.5–1.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2 (STA2, 30–500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 µM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental ([Formula: see text]100 µM). Thiopental ([Formula: see text]100 µM) also increased the TXB2 formation induced by ADP and epinephrine. Thiopental (300 µM) increased ADP- and epinephrine-induced 3H-AA release. Thiopental (300 µM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]i in the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.Key words: barbiturates, anesthetics, eicosanoids, phospholipase.

Chlorobutanol, a Preservative of Desmopressin, Inhibits Human Platelet Aggregation and Release In Vitro

1990 ◽  
Vol 64 (03) ◽  
pp. 473-477 ◽  
Author(s):  
Shih-Luen Chen ◽  
Wu-Chang Yang ◽  
Tung-Po Huang ◽  
Shiang Wann ◽  
Che-ming Teng
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Atp Release ◽  
Free Calcium ◽  
Dependent Manner ◽  
Antiplatelet Effect ◽  
Human Platelet Aggregation ◽  
Acid Pathway ◽  
Arachidonic Acid Pathway

SummaryTherapeutic preparations of desmopressin for parenteral use contain the preservative chlorobutanol (5 mg/ml). We show here that chlorobutanol is a potent inhibitor of platelet aggregation and release. It exhibited a significant inhibitory activity toward several aggregation inducers in a concentration- and time-dependent manner. Thromboxane B2 formation, ATP release, and elevation of cytosolic free calcium caused by collagen, ADP, epinephrine, arachidonic acid and thrombin respectively were markedly inhibited by chlorobutanol. Chlorobutanol had no effect on elastase- treated platelets and its antiplatelet effect could be reversed. It is concluded that the antiplatelet effect of chlorobutanol is mainly due to its inhibition on the arachidonic acid pathway but it is unlikely to have a nonspecitic toxic effect. This antiplatelet effect of chlorobutanol suggests that desmopressin, when administered for improving hemostasis, should not contain chlorobutanol as a preservative.

Testosterone Potentiation of Ionophore and ADP Induced Platelet Aggregation : Relationship to Arachidonic Acid Metabolism

1981 ◽  
Vol 46 (02) ◽  
pp. 538-542 ◽  
Author(s):  
R Pilo ◽  
D Aharony ◽  
A Raz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Unsaturated Fatty Acids ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Low Concentrations ◽  
Induced Aggregation

SummaryThe role of arachidonic acid oxygenated products in human platelet aggregation induced by the ionophore A23187 was investigated. The ionophore produced an increased release of both saturated and unsaturated fatty acids and a concomitant increased formation of TxA2 and other arachidonate products. TxA2 (and possibly other cyclo oxygenase products) appears to have a significant role in ionophore-induced aggregation only when low concentrations (<1 μM) of the ionophore are employed.Testosterone added to rat or human platelet-rich plasma (PRP) was shown previously to potentiate platelet aggregation induced by ADP, adrenaline, collagen and arachidonic acid (1, 2). We show that testosterone also potentiates ionophore induced aggregation in washed platelets and in PRP. This potentiation was dose and time dependent and resulted from increased lipolysis and concomitant generation of TxA2 and other prostaglandin products. The testosterone potentiating effect was abolished by preincubation of the platelets with indomethacin.

Effects of barbiturates on human platelet aggregation differ depending on their chemical structures

2003 ◽  
Vol 81 (8) ◽  
pp. 806-814 ◽  
Author(s):  
Masami Sato ◽  
Hideo Hirakata ◽  
Masahiro Ikeda ◽  
Kazuhiko Fukuda
Keyword(s):  
Platelet Aggregation ◽  
Calcium Concentration ◽  
Light Transmission ◽  
Human Platelet ◽  
Clinical Importance ◽  
Cytosolic Calcium ◽  
Free Calcium ◽  
Chemical Structures ◽  
Human Platelet Aggregation ◽  
Inositol 1,4,5 Trisphosphate

The effects of barbiturates on human platelet function are not fully understood. Since we have already revealed the effects and mechanisms of thiopental, thiamylal, and pentobarbital in platelets, the present study attempted to elucidate (i) the effects of other barbiturates on human platelet aggregation, (ii) the underlying mechanisms, and (iii) the structure–function relationship of barbiturates in platelets. Barbiturates, including amobarbital, butalbital, secobarbital, barbital, phenobarbital, metharbital, and primidone, were examined. Human platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, and (+)-9,11-epithia-11,12-methano-thromboxane A2 (STA2), a thromboxane A2 analog, was measured using an 8-channel light-transmission aggregometer. The cytosolic free calcium concentration ([Ca2+]i) was measured by fluorometer using fura-2 loaded platelets. Inositol 1,4,5-trisphosphate (IP3) formation induced by STA2 was determined by a commercially available IP3 assay kit. Amobarbital, butalbital, and secobarbital suppressed ADP-, epinephrine- and STA2-induced platelet aggregation and the STA2-induced [Ca2+]i increase, even when Ca2+ influx was blocked by Ni2+. However, they did not affect STA2-induced IP3 formation. Barbital, phenobarbital, metharbital, and primidone (up to 1 mM) had no effect on ADP- and epinephrine-induced platelet aggregation. Thus, we conclude that amobarbital, butalbital, and secobarbital inhibit platelet aggregation by suppressing [Ca2+]i increase without affecting IP3 formation. However, these antiaggregatory effects may not have clinical importance, since the barbiturate concentrations used were higher than clinically relevant ones. The other tested barbiturates had no effects on platelet aggregation. The data indicate that the effects of barbiturates on platelet aggregation differ depending on their chemical structures.Key words: platelet aggregation, barbiturates, cytosolic calcium concentration, inositol 1,4,5-trisphosphate.

Human Platelet Aggregation and Release Reaction Induced by Platelet Activating Factor (PAF-Acether) – Effects of Acetylsalicylic Acid and External Ionized Calcium

1985 ◽  
Vol 53 (02) ◽  
pp. 221-224 ◽  
Author(s):  
Marco Cattaneo ◽  
Maria Teresa Canciani ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Normal Subjects ◽  
Human Platelet Aggregation ◽  
Low Concentrations ◽  
Before And After ◽  
Platelet Secretion

SummaryThe effects of the cyclo-oxygenase inhibition on PAF-acether- induced human platelet aggregation and secretion are controversial. We studied the above parameters on citrated platelet-rich plasma of 12 normal subjects before and after the in vivo administration of acetylsalicylic acid (ASA). Individual sensitivities to PAF-acether were highly variable. ASA completely inhibited the platelet secretion induced by low concentrations of PAF-acether, but caused only partial inhibition when platelets were exposed to high concentrations of PAF-acether. The concentration of PAF-acether which overcame the cyclo-oxygenase inhibition varied substantially, depending on the individual sensitivity of the platelets to it. The addition of CaCl2 2 mM to the samples did not affect the extent of the platelet secretion, but increased irreversible aggregation in samples taken both before and after the ASA administration. These data suggest that low concentrations of PAF-acether stimulate the human platelet secretion by activating the cyclo-oxygenase pathway, whereas higher concentrations also trigger other mechanism(s) that suffice to induce human platelet secretion and full aggregation.

scholarly journals Inhibitory Effect of Hexahydrocurcumin on Human Platelet Aggregation

2012 ◽  
Vol 7 (7) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Huei-Ping Dong ◽  
Rei-Cheng Yang ◽  
I-Chun Chunag ◽  
Li-Ju Huang ◽  
Hsing-Tan Li ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Human Platelet Aggregation

The effects of hexahydrocurcumin on adenosine diphosphate (ADP)-induced human platelet aggregation were studied. Treatment of human platelet-rich plasma with hexahydrocurcumin resulted in an inhibitory effect on platelet aggregation, suggesting the potential of this compound as an anti-atherosclerogenic agent in humans.

Effects of Methylprednisolone and Hydrocortisone on Aggregation of Rabbit Platelets Induced by Arachidonic Acid and Other Aggregating Substances

1981 ◽  
Vol 46 (04) ◽  
pp. 676-679 ◽  
Author(s):  
Frank Glass ◽  
Howard Lippton ◽  
Philip J Kadowitz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Actual Mechanism ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
The Difference ◽  
Induced Aggregation ◽  
Dose Dependent

SummaryThe effects of methylprednisolone and hydrocortisone on platelet aggregation induced by arachidonic acid (AA), collagen, adenosine diphosphate (ADP), prostaglandin (PG) H2, and a stable PGH2 analog, were studied in platelet-rich plasma (PRP) from the rabbit. Incubation of either steroid in PRP inhibited AA-, collagen- and ADP-induced platelet aggregation in a concentration-related manner. The dose of methylprednisolone required to inhibit 0.02 mM AA-induced aggregation was lower than that required to inhibit either 0.08 μg/ml collagen or 0.2 μM ADP-induced aggregation. Methylprednisolone produced a dose dependent inhibition of platelet aggregation induced by PGH2 and the stable PGH2 analog. In washed platelets methylprednisolone was more effective in inhibiting AA-induced aggregation than ADP- or collagen-induced aggregation; however, the difference in effect was less than in PRP. Platelet responses to AA in PRP from rabbits treated with hydrocortisone or methylprednisolone, 100 mg/kg i.v., were inhibited in a transient manner, whereas aggregation induced by ADP under similar conditions was unchanged. Since inhibition of aggregation elicited by AA occurred at concentrations which do not influence PGH2-, PGH2 analog-, collagen- or ADP-induced aggregation, the present data suggest that the steroids may inhibit the incorporation, the release, or the metabolism of arachidonic acid in platelets. The actual mechanism of this relatively specific inhibition of AA-induced aggregation by anti-inflammatory steroids is uncertain but may be related to the membrane “stabilizing” properties of methylprednisolone and hydrocortisone.

Evidence for Separate Mechanisms of Induction of the Platelet Release Reaction by Collagen and Adrenaline

1975 ◽  
Author(s):  
O. Tangen ◽  
S. Bygdeman
Keyword(s):  
Platelet Aggregation ◽  
Blood Clotting ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Second Phase ◽  
Release Reaction ◽  
Human Platelet Aggregation ◽  
Small Doses ◽  
Platelet Release ◽  
Induced Aggregation

The effect of some selected inhibitors of platelet release reaction and blood clotting on collagen- and adrenaline-induced human platelet aggregation was investigated by means of the turbidimetric method according to Born. Acetylsalicylic acid (ASA) inhibited both collagen- and adrenaline-induced platelet aggregation in citrated platelet rich plasma (PRP). Addition of sufficient amounts of Ca++ to give concentrations similar to those in native blood suppressed the inhibition by small doses of ASA (5–10 μg/ml) on collagen-induced aggregation and the second phase of adrenaline-induced aggregation. Higher concentrations of ASA (13–30 μg/ml) could partly overcome this effect of Ca++. Heparin, which had no effect on primary adenosine diphosphate (ADP)-induced aggregation, inhibited platelet aggregation induced by collagen. In contrast, both the first and second phase of adrenaline-induced aggregation was markedly potentiated by heparin. Dextran sulphate had effects basically similar to heparin, Nicotinic acid inhibited collagen-induced aggregation, but had no effect on the second phase of adrenaline-induced aggregation. These results indicate that the platelet release reaction induced by collagen and adrenaline is mediated via separate receptors or reaction pathways.

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.

Human Platelet Aggregation Induced by the Synthetic Endoperoxide Analogue U-46619 is Independent From Secretion, Prostaglandin Production and Extracellular Calcium

1979 ◽  
Author(s):  
G. Di Minno ◽  
L. Bianchi ◽  
G. de Gaetano ◽  
M.J. Silver
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Acid Metabolism ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Extracellular Calcium ◽  
Reversible Aggregation ◽  
Human Platelet Aggregation ◽  
Aspirin Ingestion

U-46619 is a stable analogue of cyclic prostaglandin endoperoxides which induces human platelet aggregation independently from nucleotide secretion. We studied platelet aggregation, 14C-5 HT release and malondialdehyde (MDA) production induced by this compound in stirred or unstirred platelet-rich plasma (PRP) samples from 11 healthy volunteers. Each subject was tested both before and 90 min after aspirin ingestion (500 mg). The threshold aggregating concentration (TAC) of U-466l9 ranged between 240 and 900 nM. Aggregation was maximal between 30 and 60 min after venepuncture and was concentration-dependent (60-7, 200nM). At concentrations below the TAC, U-466l9 induced primary reversible aggregation without detectable l4C-5 HT release. At TAC or higher concentrations aggregation and release proceeded as parallel events. Neither MOA production nor intracellular LDH loss could be detected in any of the tested situations. Aspirin ingestion did not modify the above pattern of platelet responses. In unstirred samples l4C - 5 HT release occurred to the same extent as in stirred platelet suspensions. Addition to citrated PRP of Na2 - EDTA did not affect either aggregation or release. It is suggested that aggregation and secretion may be independent, parallel responses of platelet activation by U-466l9 and do not require either extracellular calcium or activation of endogenous arachidonic acid metabolism. (Supported by the Italian CNR and NIH).

Sevoflurane Inhibits Human Platelet Aggregation and Thromboxane A2Formation, Possibly by Suppression of Cyclooxygenase Activity

1996 ◽  
Vol 85 (6) ◽  
pp. 1447-1453. ◽  
Author(s):  
Hideo Hirakata ◽  
Fumitaka Ushikubi ◽  
Hiroshi Toda ◽  
Kumi Nakamura ◽  
Satoko Sai ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Scatchard Analysis ◽  
Cyclooxygenase Activity ◽  
Human Platelet Aggregation ◽  
Induced Aggregation

Background Halothane increases bleeding time and suppresses platelet aggregation in vivo and in vitro. A previous study by the authors suggests that halothane inhibits platelet aggregation by reducing thromboxane (TX) A2 receptor-binding affinity. However, no studies of the effects of sevoflurane on platelet aggregation have been published. Methods The effects of sevoflurane, halothane, and isoflurane were examined at doses of 0.13-1.4 mM. Human platelet aggregation was induced by adenosine diphosphate, epinephrine, arachidonic acid, prostaglandin G2, and a TXA2 agonist ([+]-9, 11-epithia-11, 12-methano-TXA2, STA2) and measured by aggregometry. Platelet TXB2 levels were measured by radioimmunoassay, and the ligand-binding characteristics of the TXA2 receptors were examined by Scatchard analysis using a [3H]-labeled TXA2 receptor antagonist (5Z-7-(3-endo-([ring-4-[3H] phenyl) sulphonylamino-[2.2.1.] bicyclohept-2-exo-yl) heptenoic acid, [3H]S145). Results Isoflurane (0.28-0.84 mM) did not significantly affect platelet aggregation induced by adenosine diphosphate and epinephrine. Sevoflurane (0.13-0.91 mM) and halothane (0.49-1.25 mM) inhibited secondary platelet aggregation induced by adenosine diphosphate (1-10 microM) and epinephrine (1-10 microM) without altering primary aggregation. Sevoflurane (0.13 mM) also inhibited arachidonic acid-induced aggregation, but not that induced by prostaglandin G2 or STA2, although halothane (0.49 mM) inhibited the latter. Sevoflurane (3 mM) did not affect the binding of [3H]S145 to platelets, whereas halothane (3.3 mM) suppressed it strongly. Sevoflurane (0.26 mM) and halothane (0.98 mM) strongly suppressed TXB2 formation by arachidonic acid-stimulated platelets. Conclusions The findings that sevoflurane suppressed the effects of arachidonic acid, but not those of prostaglandin G2 and STA2, suggest strongly that sevoflurane inhibited TXA2 formation by suppressing cyclooxygenase activity. Halothane appeared to suppress both TXA2 formation and binding to its receptors. Sevoflurane has strong antiaggregatory effects at subanesthetic concentrations (greater than 0.13 mM; i.e., approximately 0.5 vol/%), whereas halothane has similar effects at somewhat greater anesthetic concentrations (0.49 mM; i.e., approximately 0.54 vol/%). Isoflurane at clinical concentration (0.84 mM; i.e., approximately 1.82 vol/%) does not affect platelet aggregation significantly.

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