thromboxane-b2 and Carotid-Artery-Thrombosis

Cydonia oblonga Miller (COM) is traditionally used in Uyghur medicine for the prevention of cardiovascular disease. The present study is designed to explore the effects of COM extracts on models and markers of thrombosis and related biomarkers.. 20, 40, 80 mg/kg/day COM aqueous extracts and 5mg/kg/day aspirin, orally for 14 days were compared to untreated controls in mice on bleeding and clotting times, using the tail cutting and glass slide methods and for death rates in collagen-epinephrine pulmonary thrombosis, thrombolysis in vitro and euglobulin lysis time (ELT). In rats, common carotid artery FeCl3-induced thrombus and inferior vena cava thrombosis occlusion time, plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1α (6-keto-PGF1α) were measured.. Compared to controls, COM extracts dose-dependently prolonged bleeding by 2.17, 2.78 and 3.63 times, vs. aspirin 2.58, and the clotting time by 1.44, 2.47 and 2.48 times, vs. aspirin 1.91. COM reduced pulmonary embolus mortality by 27, 40 and 53%, vs. 47% for aspirin. COM dose-dependently increased thrombolysis by 45, 55 and 63%, vs. 56% for aspirin, and shortened ELT to 71, 61 and 43%, vs. 43% for aspirin. In rats, venous occlusion time was prolonged. Arterial and venous thrombus weights were dose-dependently reduced in COM groups. TXB2 decreased and 6-keto-PGF1α increased with COM and aspirin, with an association between 6-keto-PGF1α/TXB2 and arterial or venous thrombus weight for all products, and for occlusion time with COM but not for aspirin.. We confirm the experimental effects of COM on hemostasis and thrombosis. Further exploration of putative clinical effects appear justified.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Coagulation; Cardiovascular Agents; Carotid Artery Thrombosis; Chlorides; Collagen; Epinephrine; Ferric Compounds; Fibrinolysis; Hemostasis; Male; Mice, Inbred ICR; Phytotherapy; Plant Extracts; Plant Leaves; Pulmonary Embolism; Rats, Wistar; Rosaceae; Thromboxane B2; Vena Cava, Inferior; Venous Thrombosis

To screen the main component of Dahuangzhechong pill's anti-arterial thrombosis with the orthogonal design and refine Dahuangzhechong pills.. In accordance with the orthogonal design table (L(16)2(15)), divided herbs into 16 groups and made the appropriate liquid. The liquid was gave to SD rats by intragastric administration,the model group, normal control group received the same volume of physiological saline. Isolated rats' carotid artery after intragastric administration a week,modeled according to ferric chloride inducement the carotid artery thrombosis method, then collected blood, detected content of platelet, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), sheared and measured dry weight of the modeling artery, then placed arteries in 10% formalin fixation, observed morphological changes in vascular tissue by HE staining.. Pathological examination revealed: each experimental group had thrombosis, softening, dissolution, absorption, and intimal injury, but the severity of thrombosis were diferent. Orthogonal analysis showed: 1, influence on dry weight of thrombus: rhubarb, ground beetle, leeches, peach seed, dry paint, except dry paint P<0.05, the others P<0.01.2, influence on plasma 6- keto-PGF1alpha level: peach seed, dry paint, ground beetle, gadfly, grubs, leeches, rhubarb, except rhubarb P<0.05, the others P<0.01.3, influence on plasma TXB2: ground beetle, peach seed, dried paint, rhubarb, leeches, except leech P<0.05, the others P<0.01.4, influence on platelet count: peach seed, dry paint, rhubarb, ground beetle, gadfly, leeches, except gadfly, leeches P<0.05, the others P<0.01.. Anti-artery thrombosis of Dahuangzhechong Pill is most closely related with rhubarb, ground beetle, leeches, peach seed, dry paint and gadfly.

Topics: 6-Ketoprostaglandin F1 alpha; Analysis of Variance; Animals; Carotid Artery Thrombosis; Carotid Artery, Common; Disease Models, Animal; Drug Combinations; Drugs, Chinese Herbal; Female; Fibrinolytic Agents; Platelet Aggregation; Random Allocation; Rats; Rats, Sprague-Dawley; Rheum; Thrombolytic Therapy; Thromboxane B2

A combination of low-dose aspirin (ASA) and a phosphodiesterase inhibitor has been clinically tried for the secondary prevention of atherothrombotic diseases. The in vivo antithrombotic property of ibudilast (CAS 50847-11-5), a phosphodiesterase 4 (PDE4) inhibitor, was evaluated in a photochemically-induced guinea pig carotid artery thrombosis model in combination with low-dose ASA. The time required to decrease the carotid artery blood flow to the reading "zero" was defined as the time to occlusion (TTO) of the artery through thrombogenesis. Each independent use of ASA (300 mg/kg, p.o.) and ibudilast (3 and 10 mg/kg, p.o.) significantly prolonged the TTO, and ASA (300 mg/kg) significantly increased bleeding time (BT) and gastric mucosal injury. A selective PDE4 inhibitor rolipram (1 and 5 mg/kg, p.o.) tended to prolong the TTO without extending BT. ASA (100 mg/kg) plus ibudilast (3 mg/kg) and ASA (100 mg/kg) plus rolipram (5 mg/kg) markedly prolonged the TTO compared with each agent alone. Interestingly, ASA (100 mg/kg) plus ibudilast (3 mg/kg) caused a longer TTO than ASA (300 mg/kg) alone, without significant extension of BT and gastric mucosal injury as observed in ASA (300 mg/kg). These results indicate that the combination of low-dose ASA and ibudilast has a more potent antithrombotic effect than ASA alone without increasing bleeding tendency and gastric mucosal injury. The potent in vivo antithrombotic effect of this combination may be brought about by an action that is associated with PDE4 inhibition of ibudilast.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aspirin; Bleeding Time; Carotid Artery Thrombosis; Drug Therapy, Combination; Gastric Mucosa; Guinea Pigs; Immunoenzyme Techniques; Indicators and Reagents; Male; Mice; Phosphodiesterase Inhibitors; Photochemistry; Platelet Aggregation Inhibitors; Pyridines; Rolipram; Salicylic Acid; Stomach Diseases; Thromboxane B2

Target levels of ex vivo inhibition of platelet aggregation (IPA) induced by adenosine diphosphate (ADP) that produce clinically relevant effects of clopidogrel, a P2Y12 antagonist, are unclear. We examined standard and modified IPA and P2Y12 receptor occupancy as predictors of antithrombotic (% thrombus weight reduction) and bleeding time (BT, fold-increase over control) effects of clopidogrel in rabbit models of carotid artery thrombosis and cuticle bleeding, respectively. Standard and modified IPA with 20 microM ADP were measured in the absence and presence of partial P2Y1 blockade, respectively. Clopidogrel maximally produced standard IPA of 57% +/- 5%, antithrombotic effect of 85% +/- 1%, BT increase of 6.0 +/- 0.4-fold and P2Y12 receptor occupancy of 87% +/- 5%. Surprisingly, a clopidogrel dose that produced a low standard IPA of 17% +/- 4% and P2Y12 receptor occupancy of 39% +/- 5% achieved a significant antithrombotic activity of 55% +/- 2% with a moderate increase in BT of 2.0 +/- 0.1-fold. This underestimation of clopidogrel efficacy by standard IPA was improved by measuring either modified IPA or P2Y12 receptor occupancy. These results suggest that in clopidogrel-treated rabbits, low standard IPA is associated with significant antithrombotic effects. Moreover, modified IPA and P2Y12 receptor occupancy appear to better predict the magnitude of clopidogrel's efficacy compared with standard IPA, which may be a better predictor of BT.

Topics: Adenosine Diphosphate; Analysis of Variance; Animals; Aspirin; Biomarkers; Bleeding Time; Blood Platelets; Carotid Artery Thrombosis; Carotid Artery, Common; Clopidogrel; Disease Models, Animal; Dose-Response Relationship, Drug; Hemostasis; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Predictive Value of Tests; Protein Binding; Rabbits; Receptors, Purinergic P2; Regional Blood Flow; Thromboxane B2; Ticlopidine

Effects of scorpion venom active polypeptide (SVAP) from scorpion venom of Buthus Martensii Karsch of Chinese on platelet aggregation in ex vivo and vitro in rabbits, thrombosis in carotid artery of rats and plasma 6-keto-PG F1alpha and TXB2 in rats were studied by the turbidimetry, the duplicated thrombosis model by electrostimulation and RIA, respectively. The results showed that SVAP 0.125, 0.25, 0.5 mg/ml inhibited significantly the rabbit platelet aggregation triggered by 0.3 U/ml thrombin, 10 microM ADP in vitro (P<0.05 or 0.01) and SVAP at the dose of 0.32, 0.64 mg/kg iv prolonged distinctively the occlusion time of thrombosis that were induced by electrical stimulation. Increased% of 0.16, 0.32 and 0.64 mg/kg were 30.16, 71.74, 98.27%, respectively, which showed a good dose-effect relationship. SVAP 0.22 mg/ml (in vitro) or 0.2, 0.4 mg/kg (in ex vivo) could obviously increase the plasma concentration of 6-keto-PG F1alpha, but slightly effect rats plasma concentration of TXB2 in vitro and in ex vivo and significantly increase of value of PG I2/TXA2, which suggested that the mechanism of the antithrombotic action of SVAP is related to the resistance against platelet aggregation, increase of the concentration of PG I2 in plasma.

Topics: 6-Ketoprostaglandin F1 alpha; Analysis of Variance; Animals; Blood Platelets; Carotid Artery Thrombosis; China; Electric Stimulation; Peptides; Platelet Aggregation; Rabbits; Rats; Rats, Wistar; Scorpion Venoms; Scorpions; Thromboxane B2

To study the inhibitory effects of nimodipine (Nim) on rat platelet aggregation and arterial thrombosis in vivo.. The aggregation rate of platelets induced by ADP and inhibition rate of Nim were measured by the change of light transmission. Effect of Nim on arterial occlusion time was measured by electric stimulation. Effect of Nim on the contents of 6-keto-PGF1 alpha and TXB2 in serum was measured by radioimmunoassay.. Nim 4.5, 9, 18, and 36 mg.kg-1.d-1 ig for 4 d restrained the platelet aggregation. The IC50 (95% confidence limits) was 26 (9-44) mg.kg-1. Nim 4.5, 9, and 18 mg.kg-1.d-1 ig for 4 d markedly prolonged the time of thrombotic occlusion in carotid artery induced by electric stimulation. Nim 9 and 18 mg.kg-1.d-1 improved the imbalance of 6-keto-PGF1 alpha/TXB2 in serum after thrombosis.. Nim was a potent inhibitor of platelet aggregation, which was partially concerned with the improved balance of 6-keto-PGF1 alpha/TXB2.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Carotid Artery Thrombosis; Dose-Response Relationship, Drug; Male; Nimodipine; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Thromboxane B2

To study the effect of 3,4',5-trihydroxystibene-3-beta-mono-D-glucoside (Polydatin, Pol) on rabbit arterial thrombosis.. Rabbit arterial thrombosis was induced by vascular endothelial damage with trypsin.. It was showed that the moist weights of the thrombus were 6.6 +/- 1.8 and 4.8 +/- 1.6 mg in Pol 5 and 10 mg.kg-1 groups, respectively, which was lighter than that in control (10.9 +/- 1.9 mg, P < 0.05, P < 0.01); the platelet aggregation was inhibited simultaneously. In vitro, Pol 0.30-1.15 mmol.L-1 reduced TXA2 produced in platelets. It did not affect the production of PGI2 in cultured human umbilical vein endothelial cells.. Thrombosis was abated by Pol. The selective inhibition of production of TXA2 rather than PGI2, is one of the mechanisms involved.

Topics: Animals; Carotid Artery Thrombosis; Endothelium, Vascular; Female; Glucosides; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Stilbenes; Thromboxane B2

The combination of thromboxane (TX) synthase inhibition and prostaglandin (PG) H2/TXA2 receptor antagonism yields enhanced antithrombotic effects as compared with either intervention alone. However, it is not known whether the enhancing effect of TX synthase inhibition is expressed also in the presence of complete blockade of PGH2/TXA2 receptors. Thus we evaluated the antithrombotic effects of increasing doses of the PGH2/TXA2 receptor antagonist L 670596 alone and in combination with a dose of the TX synthase inhibitor FCE 22178 causing > 95% inhibition of platelet TXB2 production. In the dog model of electrically induced coronary thrombosis, occlusion time in control animals (n = 14) averaged 72 +/- 29 min. L 670596 alone dose-dependently antagonized platelet PGH2/TXA2 receptors and prolonged occlusion time. The addition of FCE 22178 displaced the dose-occlusion time relation of L 670596 in a parallel fashion without modifying receptor occupancy. In the rabbit model of copper coil-induced carotid artery thrombosis, occlusion was very rapid (14 +/- 4 min) in control animals (n = 17) and was not modified by either aspirin or FCE 22178. L 670596 caused a dose-related receptor blockade and prolongation of occlusion time. The association with FCE 22178 enhanced significantly the antithrombotic effect of L 670596 at all doses. We conclude that the full therapeutic potential of PGH2/TXA2 receptor antagonism is expressed at > 90% platelet receptor occupancy. The additive effect of TX synthase inhibition suggests that conversion of PGH2 to platelet-inhibitor and vasodilator prostaglandins might be of therapeutic importance, irrespective of the extent of PGH2/TXA2 receptor blockade.

Topics: Animals; Carbazoles; Carotid Artery Thrombosis; Copper; Coronary Thrombosis; Disease Models, Animal; Dogs; Evaluation Studies as Topic; Imidazoles; Male; Naphthalenes; Platelet Aggregation; Prostaglandin H2; Prostaglandins H; Rabbits; Receptors, Prostaglandin; Receptors, Thromboxane; Receptors, Thromboxane A2, Prostaglandin H2; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

To clarify the role of thromboxane (TX) A2 in arterial thrombus formation, we examined the antithrombotic effects of both a TXA2 synthetase inhibitor (CV-4151) and a TXA2 receptor antagonist (AA-2414) on the rabbit common carotid artery thrombosis which was induced by injury of the endothelium by treatment with 0.25% pronase solution. CV-4151 (1,10 mg/kg, p.o.) and AA-2414 (10 mg/kg, p.o.) significantly inhibited thrombus formation. Furthermore, the combined use of CV-4151 and AA-2414 (0.1 mg/kg, p.o. each) significantly inhibited thrombus formation, though these drugs at the same doses had no effect when administered singly. The plasma level of 11-dehydro TXB2 increased significantly during thrombus formation, and CV-4151 (10 mg/kg) markedly inhibited this increase. There was a significant correlation between the in vivo antithrombotic effects of these drugs and their ex vivo inhibitory effects on arachidonic acid-induced platelet aggregation. The antithrombotic effect of CV-4151 also correlated significantly with its ability to inhibit the production of serum TXA2. These results show that TXA2 may play an important role in the thrombus formation in arterial thrombosis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Benzoquinones; Carotid Artery Thrombosis; Disease Models, Animal; Endothelium, Vascular; Fatty Acids, Monounsaturated; Heptanoic Acids; Male; Platelet Aggregation; Pyridines; Quinones; Rabbits; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase

Acute thrombosis was induced in the carotid arteries of anaesthetised rabbits by local electrical stimulation (1mA for 2 min) of the vessel wall. Histological findings confirmed the platelet-rich composition of the thrombus. Platelet accumulation at the stimulus site was quantitated with "'Indium-labelling of autologous platelets. In rabbits injected intravenously with either 2 mg/kg dazoxiben or 10 mg/kg aspirin, accumulation of labelled platelets was considerably reduced. Animals which received vehicle injection only, showed no such reduced thrombus formation. In separate experiments in anaesthetised rabbits, the levels of TxB2 and 6KPGF1 alpha in clotting blood were measured in blood samples taken from animals which had received the above drug treatments. Aspirin markedly reduced the production of both arachidonate metabolites. In contrast, dazoxiben almost totally inhibited TxB2 production but caused a 3.5 fold increase in the levels of 6KPGF1 alpha. These findings demonstrate an anti-thrombotic effect and confirm the mechanistic selectivity of a thromboxane synthetase inhibitor.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Aspirin; Carotid Artery Thrombosis; Cells, Cultured; Enzyme Inhibitors; Fibrinolytic Agents; Imidazoles; In Vitro Techniques; Oxidoreductases; Platelet Aggregation; Rabbits; Thromboxane B2; Thromboxane-A Synthase