The Effects of Modulation of Prostanoid Metabolism on the Thoracic Platelet Accumulation Induced by Intravenous Administration of Collagen in the Guinea-Pig

1986 ◽  
Vol 56 (03) ◽  
pp. 263-267
Author(s):  
K D Butler ◽  
R A Shand ◽  
R B Wallis
Keyword(s):  
Platelet Count ◽  
Guinea Pig ◽  
Intravenous Administration ◽  
Cyclooxygenase Inhibitors ◽  
Concomitant Increase ◽  
Thromboxane Synthetase ◽  
Platelet Accumulation ◽  
Related Increase

SummaryThe effects of intravenously administered collagen on the circulatory platelet count, TxB2, 6-keto PGF1α and 51Cr-labelled platelet accumulation in the thorax have been evaluated in the guinea-pig. Administration of collagen induced a dose-related peripheral thrombocytopenia and a concomitant increase in 51Cr-labelled platelets in the thorax. There was also a transient dose-related increase in plasma TxB2 but no change in plasma 6-keto PGF1α levels.The thromboxane synthetase inhibitors tested, reduced the platelet accumulation, but only CGS 13080 significantly inhibited TxB2 production. In contrast all the cyclooxygenase inhibitors tested impaired the elevation of plasma TxB2 after collagen, but only diclofenac inhibited the 51Cr-labelled platelet accumulation.The greater effect of thromboxane synthetase inhibitors compared to cyclooxygenase inhibitors on platelet accumulation in this system cannot be completely explained by the changes measured in the circulating prostanoids.

Intrathoracic Platelet Accumulation in the Guinea-Pig Induced by Intravenous Administration of Arachidonic Acid - Effect of Cyclooxygenase and Thromboxane Synthetase Inhibitors

1986 ◽  
Vol 56 (03) ◽  
pp. 311-317 ◽  
Author(s):  
P A Barrett ◽  
K D Butler ◽  
R A Shand ◽  
R B Wallis
Keyword(s):  
Arachidonic Acid ◽  
Blood Volume ◽  
Intravenous Administration ◽  
Guinea Pigs ◽  
Human Albumin ◽  
Thromboxane Synthetase ◽  
Acid Effect ◽  
Rapid Accumulation ◽  
Platelet Accumulation ◽  
High Doses

SummaryIntravenous administration of arachidonic acid to guinea-pigs caused a dose-related, rapid accumulation of 51Cr-labelled platelets in the thorax. Inhibitors of cyclooxygenase inhibited the platelet accumulation, induced by arachidonic acid (30 mg/kg), at doses which did not alter the thoracic blood volume (as measured by 131I-labelled human albumin). Thromboxane synthetase inhibitors had different effects on platelet accumulation depending on the dose. CGS 12970 (3 mg/kg) and N(1-carboxyheptyl) imidazole (100 mg/kg) reduced platelet accumulation. High doses of CGS 12970 and CGS 13080 caused an apparent enhancement of platelet accumulation which was associated with pooling of blood in the thorax, as measured by either 131I-labelled human albumin or 51Cr-labelled erythrocytes. This increase in thoracic blood volume was abolished if the guinea-pigs were also pretreated with diclofenac (1 mg/kg) in addition to the thromboxane synthetase inhibitor. Increases in thoracic blood volume were also obtained following infusions of PGI2 but not PGD2 or PGE2.

scholarly journals Effects of an antiplatelet glycoprotein Ib antibody on hemostatic function in the guinea pig

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 690-694 ◽  
Author(s):  
BH Becker ◽  
JL Miller
Keyword(s):  
Animal Model ◽  
Platelet Count ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Bleeding Time ◽  
Model System ◽  
Platelet Counts ◽  
Equal Dose ◽  
Guinea Pig Model

Abstract Previous studies in the guinea pig model system have established a close structural homology between human and guinea pig glycoproteins Ib (GPIb) and IIb/IIIa (GPIIb/IIIa). Moreover, the murine monoclonal antibody (MoAb) PG-1, which recognizes GPIb in guinea pig platelets and megakaryocytes, exerted full inhibition on von Willebrand factor (vWF)- dependent platelet agglutination without inhibiting aggregation induced by ADP, collagen, or thrombin. The present research extends this animal model system to study of the effects on hemostatic function following the in vivo injection of MoAb PG-1 or its F(ab')2 fragments. A hind limb template bleeding time methodology was developed for use in guinea pigs. Normal bleeding time was determined to be 2.7 +/- 0.5 minutes (mean +/- SD), with an observed range of two to four minutes. Platelet counts in these same animals were 501 +/- 82 x 10(3)/microL. After intraperitoneal (IP) injection of busulfan, guinea pigs became increasingly thrombocytopenic. As long as the platelet count remained above approximately 150 x 10(3)/microL, the bleeding time was not more than five minutes; however, further decrease in the platelet count was accompanied by more marked prolongations of the bleeding time. For 14 to 72 hours after IP injection of 1.3 mg/kg intact PG-1 MoAb, a hemorrhagic state was produced with a bleeding time greater than 20 minutes. The platelet count concurrently decreased to approximately 50% of its baseline value but could not be further decreased either by raising the initial PG-1 dosage tenfold or by administering a second, equal dose 24 hours after the initial injection. This finding may reflect a heterogeneity of circulating platelets with respect to GPIb, to Fc receptors, or to an interaction between them. After IP injection of 0.63 to 2.5 mg/kg PG-1 F(ab')2 fragment, platelet counts did not decrease more than 21% below baseline levels in a 72-hour period, and bleeding times never increased by more than one minute over baseline values. Nevertheless, platelets obtained from animals 24 hours after injection of 2.5 mg/kg PG-1 F(ab')2 showed full inhibition of agglutination induced by ristocetin. The response of these platelets to aggregation by asialo-vWF was also severely inhibited as compared with control platelets. PG-1 F(ab')2 produced no effect on aggregation induced by ADP. These studies show that virtually complete functional block of the vWF receptor by F(ab')2 fragments of the anti-GPIb MoAb PG- 1 is not sufficient to produce a hemorrhagic state in the guinea pig animal model system.

Distribution of cisplatin in perilymph and cerebrospinal fluid after intravenous administration in the guinea pig

1995 ◽  
Vol 36 (1) ◽  
pp. 83-86 ◽  
Author(s):  
Goran Laurell ◽  
Anita Andersson ◽  
Berit Engstr�m ◽  
Hans Ehrsson
Keyword(s):  
Cerebrospinal Fluid ◽  
Guinea Pig ◽  
Intravenous Administration

scholarly journals Role of Prostaglandins in Blood-Induced Vasoconstriction of Canine Cerebral Arteries

1988 ◽  
Vol 8 (1) ◽  
pp. 109-115 ◽  
Author(s):  
Sally A. Lang ◽  
Michael B. Maron
Keyword(s):  
Arachidonic Acid ◽  
Vascular Resistance ◽  
Topical Application ◽  
Cerebral Arteries ◽  
Cyclooxygenase Inhibitors ◽  
Prostaglandin E ◽  
Constant Flow ◽  
Thromboxane Synthetase ◽  
By Products

We tested the hypothesis that the vasoconstriction produced by the application of blood to the adventitial surfaces of the vessels of an isolated perfused canine circle of Willis preparation was mediated by products of prostaglandin metabolism. In this preparation (perfused at constant flow and outflow pressure), topical application of blood produced an average 16.6 ± 1.8 (SE) mm Hg increase in inflow pressure. This response could be prevented with four structurally dissimilar cyclooxygenase inhibitors (aspirin, indomethacin, ibuprofen, and meclofenamate), suggesting that the blood-induced increase in vascular resistance was mediated by prostaglandins. Imidazole, an inhibitor of thromboxane synthetase, had no effect on the blood response. Further support for the involvement of prostaglandins in this response was provided by additional experiments in which either arachidonic acid, prostaglandin E2 (PGE2), or PGF2α were administered. All three treatments produced vasoconstriction. These results suggest that the vessels of this preparation are capable of synthesizing vasoconstrictor prostaglandins and indicate that they are reactive to known vasoactive prostaglandins.

Comparative Kinetics of Serum and Vitreous Humor Digoxin Concentrations in a Guinea Pig Model. Part I: Intravenous Administration of Digoxin

1991 ◽  
Vol 15 (2) ◽  
pp. 60-62 ◽  
Author(s):  
B. Donnelly ◽  
J. Balkon ◽  
J. H. Bidanset ◽  
A. Belmonte ◽  
M. Barletta ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Intravenous Administration ◽  
Vitreous Humor ◽  
Pig Model ◽  
Guinea Pig Model ◽  
Kinetics Of

The adolescent emotional maelstrom

2008 ◽  
Vol 3 (1) ◽  
pp. 9-28
Author(s):  
Renata F.I. Meuter ◽  
Leigh Buckley
Keyword(s):  
Simon Task ◽  
Lexical Representation ◽  
Concomitant Increase ◽  
Attention Task ◽  
Response Latencies ◽  
Emotion Words ◽  
Inhibitory Ability ◽  
Age Related ◽  
Emotion Representation ◽  
Related Increase

To determine how differences in emotion representation and/or inhibitory ability affect adolescents’ responses to emotion words, 13-yr and 16-yr olds, as well as adults, were compared on the processing of emotion-laden and neutral words. Word ratings revealed that 16-yr olds tended towards perceiving all words as more arousing than did adults, irrespective of valence. Also, they rated words more negatively than 13-yr olds. Performance on an Affective Simon task revealed a marked incongruency effect only for 13-yr olds (and then only for negative words) but not for 16-yr olds (who responded fastest) or adults. Performance on a sustained attention task confirmed the expected age-related increase in inhibitory ability and a concomitant increase in response latencies. Our conclusions are two-fold. First, there are age-related differences in lexical representation which appear more marked for 16-yr olds. Second, 16-yr olds are more reactive, irrespective of the emotional content they are processing, yet appear to control its impact as efficiently as adults.

The Evaluation of a Method for Adenosine Diphosphate Induced Platelet Aggregation in the Guinea Pig

1971 ◽  
Vol 25 (01) ◽  
pp. 030-040 ◽  
Author(s):  
R. D Mackenzie ◽  
J. G Henderson ◽  
J. M Steinbach
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Guinea Pig ◽  
Adenosine Diphosphate ◽  
Infusion Time ◽  
Platelet Response ◽  
In Vivo Measurement ◽  
Platelet Concentration ◽  
Platelet Aggregates

SummaryA method is described for the in vivo measurement of ADP-induced platelet aggregation in the guinea pig. This method uses the property of the lungs to remove platelet aggregates from the circulation. ADP is infused into the jugular vein and blood samples are removed from the carotid artery for determination of platelet concentration.In order to find a practical concentration of ADP and infusion time, the effects of several concentrations and infusion time on platelet count versus time were determined. A dose of 0.2 mg/kg ADP infused over 1 min was found to produce an approximately 50% drop in platelet count with a return to the original level at about 30 min. The analysis of the platelet response to ADP can be made quantitative by measurement of the total response, that is, the total decrease of platelet count from start of infusion to the return to preinfusion values.Prostaglandin E1 was tested and found to inhibit the total aggregation response with this method.

Evidence for a Direct Effect on Vascular Permeability of Platelet-Activating Factor Induced Hemoconcentration in the Guinea Pig

1985 ◽  
Vol 54 (04) ◽  
pp. 756-759 ◽  
Author(s):  
Dean A Handley ◽  
Mark L Lee ◽  
Robert N Saunders
Keyword(s):  
Guinea Pig ◽  
Vascular Permeability ◽  
Calcium Channel Blockers ◽  
Platelet Activating Factor ◽  
Channel Blockers ◽  
Heptanoic Acid ◽  
Thromboxane Synthetase ◽  
Specific Antagonist ◽  
Protein Rich ◽  
Prior Administration

SummaryThe ability of synthetic platelet-activating factor (PAF) given intravenously to produce loss (extravasation) of protein rich plasma (resulting in hemoconcentration) has been examined using guinea pigs. Hemoconcentration induced by PAF was not prevented by prior administration of inhibitors of thromboxane synthetase (7-(3-pyridyl)heptanoic acid, UK-37,248-01), PGI2, aspirin, indomethacin or antiserum induced thrombocytopenia. Calcium channel blockers (nifedipine, verapamil, diethyl-amino octyltrimethoxybenzoate, diltiazem), antihistamines (pyrilamine, cimetidine, diphenhydramine), or the elevator of cAMP IBMX were ineffective in blocking PAF-induced hemoconcentration. In contrast, CV-3988, reported to be a specific antagonist to PAF, was 98% inhibitory of PAF extravasation when given i. a. at 3.5 mg/kg. The ED50 was 0.14 mg/kg I. A. and 15 mg/kg p.o. against 75 ng/kg PAF. These data suggest that PAF-induced hemoconcentration involves receptor mediated alterations of vascular permeability that are inhibited by a specific PAF antagonist.

Thrombocytopaenia, Thromboxane And Prostacyclin Production During The Forssman Reaction In The Guinea-Pig: Effect Of A Thromboxane Synthetase Inhibitor

1981 ◽  
Author(s):  
J Westwick ◽  
K Butler ◽  
A Honey ◽  
S Krishnamurthi ◽  
V V Kakkar
Keyword(s):  
Guinea Pig ◽  
Post Injection ◽  
Blood Samples ◽  
Synthetase Inhibitor ◽  
Thromboxane Synthetase Inhibitor ◽  
Thromboxane Synthetase ◽  
Thromboxane Production ◽  
Antigen Antibody ◽  
Prostacyclin Production ◽  
Forssman Antibody

Intra venous (iv) injection of Forssman antibody into the guinea-pig (GP) is known to result in a rapid antigen antibody reaction in the lungs leading to bronchospasm and thrombocytopaenia. Death as a result of Forssman shock has been shown to be complement and platelet dependentGroups of 5 Duncan-Hartley GP (350-400g) received either 0.2ml (sub lethal groups) or 0.6ml (lethal groups) of rabbit anti Forssman antiserum (RAFA) iv, then 5ml blood samples were collected via carotid artery cannula, into 0.5ml ice cold EDTA (lOOmM) and indomethacin (180μM) mixture at 0, 1, 3 and 5 min. post injection. The blood samples were rapidly centrifuged at 15,000g for 3 min, plasma removed and frozen at -20°C until assayed. The plasma was then assayed for TxB2 and 6-oxo-PGF1α using specific RIA’s. There was a marked TxB2 production during the thrombocytopaenia with a concomitant small increase in 6-oxo-PGF1α production.However, when groups of 5 GPs were dosed iv with 0, 1, 3 or 10 mg/kg of UK-37, 248, a potent and selective thromboxane synthetase inhibitor, 3 mins prior to 0.2ml of RAFA the resulting thrombocytopaenia was not inhibited at 0, 0.5, 1, 2, 5, 10 and 15 min post RAFA. Thus thromboxane production does not appear to be contributory to the Forssman induced thrombocytopaenia in the GP.

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