thromboxane-b2 and Thrombophlebitis

This investigation sought to determine how different components of the hemostatic system affect the development of venous thrombosis in rats displaying hyperlipidemia, either on a genetic basis or secondary to metabolic disorders. On employing an experimental model of collagen-triggered venous thrombosis, both spontaneously hyperlipidemic (Yoshida strain) and streptozotocin-induced diabetic rats generated about 2.3-fold greater thrombi than normolipidemic controls. This was associated with significant platelet activation, as revealed by increased levels of serum thromboxane B2 in diabetics (1.5-fold) as well as in Yoshida (8-fold) rats, in comparison with controls. In contrast, ex vivo total fibrinolytic activity, as measured by euglobulin lysis time, did not differ between normo- and hyperlipidemic or diabetic animals. Plasminogen activator inhibitor activity was lower in both Yoshida and diabetic rats than in controls. However, tissue-type plasminogen activator activity was differently affected by the genetic or the diabetes-related hyperlipidemia, showing significantly lower values in Yoshida (-26%), but significantly higher values in diabetic rats (+29%) than in normolipidemic controls. We conclude that platelet activation, rather than consistent modifications of the fibrinolytic system, is likely to influence the enhanced thrombus development associated with primary or secondary forms of hyperlipidemia.

Topics: Animals; Disease Models, Animal; Fibrinolysis; Hyperlipidemias; Male; Platelet Activation; Rats; Rats, Inbred BN; Rats, Inbred Strains; Rats, Sprague-Dawley; Thrombophlebitis; Thromboxane B2

The antiplatelet and antithrombotic activities of LCB 2853 (sodium 4-[[1-[[[(4-chlorophenyl)sulfonyl]amino]methyl]cyclopentyl] methyl]benzeneacetate, CAS 141335-11-7) a novel thromboxane A2 (TXA2) receptor antagonist were examined after intravenous administration. The correlation between LCB 2853 plasma concentration and ex vivo inhibition of arachidonic acid-induced aggregation was observed in rats, for 4 h, as long as LCB 2853 was detected in plasma by HPLC analysis. Pharmacokinetic parameters were determined. The antithrombotic activity was tested in arterial and venous thrombosis models. In dog coronary stenosis, LCB 2853 shown a very high efficacy (ED50 = 7.2 micrograms/kg), whereas acetylsalicylic acid (ASA) was only active at 3.2 mg/kg and ticlopidine was ineffective at 12.8 mg/kg. In rat venous thrombosis induced by combination of venous injury and blood stasis, perfused LCB 2853 decreased the weight of thrombi in a dose related manner (ED50 = 220 micrograms/kg/min). In a comparative study, at 250 micrograms/kg/min, ticlopidine was less potent and ASA failed to show any protection. The potent immediate efficacy of LCB 2853 and the advantageous comparisons with ASA (which was ineffective in some models) or ticlopidine (which needs metabolization lag time) observed in many models suggest that this compound may have beneficial effects in patients with TXA2-associated disturbances.

Topics: Animals; Chromatography, High Pressure Liquid; Coronary Thrombosis; Dogs; Female; Fibrinolytic Agents; Injections, Intravenous; Male; Phenylacetates; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Receptors, Thromboxane; Sulfonamides; Thrombophlebitis; Thromboxane B2

We have recently demonstrated that contact activation of the intrinsic coagulation cascade in vitro is accompanied not only by thromboxane (TX) B2 generation but also by the formation of 5-lipoxygenase-derived cysteinyl-leukotrienes (LT). In our present study we have investigated the effects of the vascular wall on the eicosanoid formation by whole human blood. Incubation of whole human blood in clamped segments of autologous umbilical veins incubated in oxygenated Tyrode solution led to a time-dependent generation of cysteinyl-LT and TXB2 in the blood samples. A clear dissociation in the time-dependent production profiles was observed with cysteinyl-LT practically reaching a plateau phase at 60 min while TXB2 levels increased up to 90 min. In blood samples incubated in glass tubes for 60 min TXB2 production was about 13 times higher and cysteinyl-LT formation only about half as much as in the umbilical vein segments indicating a differential stimulation of both the cyclooxygenase and 5-lipoxygenase pathway of arachidonic acid metabolism in these experiments. By reverse phase HPLC the immunoreactive cysteinyl-LT were identified as a mixture of LTC4, LTD4 and LTE4. Since the data were suggestive of intravascular cysteinyl-LT formation in thrombotic vessels, thrombus specimens from patients with acute deep vein thrombosis of the lower limb were analysed for these compounds by combined reverse phase HPLC and specific radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Arachidonate 5-Lipoxygenase; Blood Coagulation; Constriction; Humans; Infant, Newborn; Leukotriene C4; Leukotriene D4; Leukotriene E4; Thrombophlebitis; Thrombosis; Thromboxane B2; Umbilical Veins

Rhynchophylline (Rhy) inhibited rabbit platelet aggregation induced by arachidonic acid (AA), collagen, and ADP. The values of IC50 were 0.72, 0.74, and 0.67 mmol.L-1, respectively. Rhy reduced the thromboxane B2 (TXB2) generation in PRP induced by collagen but failed to reduce that induced by AA. Rhy suppressed malondialdehyde (MDA) formation in platelet suspension stimulated by thrombin, inhibited the platelet factor 4 (PF4) release. It did not alter intraplatelet cAMP concentration. Rhy 10-20 mg.kg-1 iv showed a significant inhibition of venous thrombosis and cerebral thrombosis in rats.

Topics: Alkaloids; Animals; Cyclic AMP; Indole Alkaloids; Intracranial Embolism and Thrombosis; Male; Malondialdehyde; Oxindoles; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Factor 4; Rabbits; Rats; Rats, Inbred Strains; Thrombophlebitis; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; beta-Thromboglobulin; Blood Coagulation Tests; Catecholamines; Cyclic AMP; Female; Fibrinolysis; Hemodynamics; Humans; Incidence; Male; Platelet Aggregation; Quadriplegia; Spinal Cord Injuries; Thrombophlebitis; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dogs; Pancreas Transplantation; Platelet Aggregation; Thrombophlebitis; Thrombosis; Thromboxane B2; Time Factors

The urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha (the major urinary metabolites of thromboxane B2 and prostacyclin) was measured in ten patients with confirmed deep vein thrombosis, using specific methods based on gas chromatography - mass spectrometry with deuterium-labelled internal standards. Measurements of these major urinary metabolites makes it possible to monitor the in vivo formation of thromboxane A2 and prostacyclin. The results demonstrate an abnormally high and very variable excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha in patients with deep vein thrombosis. This indicate that both thromboxane A2 and prostacyclin are involved in the course of events associated with this disease.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Blood Platelets; Epoprostenol; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Thrombophlebitis; Thromboxane A2; Thromboxane B2; Thromboxanes; Time Factors

Platelet activation occurs in the initial phase of venous thrombus formation. To determine if thromboxanes (Tx) are released during this process and if Tx measurements are useful in the diagnosis, urinary immunoreactive TxB2 was measured by a rapid, inexpensive assay in 100 consecutive patients with suspected thromboembolic disease. Urinary iTxB2 was not increased in patients who took aspirin, nor in patients studied several weeks after onset of symptoms. Of the remaining patients, iTxB2 was increased in 11 of 15 with confirmed deep vein thrombosis and in seven of ten with confirmed pulmonary emboli. Of the 54 patients in whom acute thrombosis was excluded, iTxB2 was increased in only four (7 percent). A second study evaluated 25 additional patients with nondiagnostic lung scans who required pulmonary angiography; iTxB2 was increased in seven of ten with positive angiograms and in 0 of 15 with negative angiograms. The three patients with negative iTxB2 and positive angiograms were receiving heparin when studied. These data suggest that, in the absence of aspirin, platelet Tx is released during thrombus formation. In combination with other noninvasive tests, urinary iTxB2 is a useful adjunct to diagnosing acute thromboembolic disease.

Topics: Angiography; Aspirin; Humans; Lung; Platelet Function Tests; Pulmonary Embolism; Radioimmunoassay; Thrombophlebitis; Thromboxane B2; Thromboxanes

The production of 6-keto-PGF1 alpha and thromboxane B2 (TxB2) was determined in vitro in hand veins from 35 patients with deep venous thrombosis (DVT), 13 patients with stroke and 14 controls. The TxB2 production was significantly increased, approximately doubled, in patients with DVT and unchanged in patients with stroke. The production of 6-keto-PGF1 alpha was significantly increased in both groups. It is suggested that the increased production of TxB2 might be contributory to thrombosis.

Topics: Adolescent; Adult; Aged; Cerebrovascular Disorders; Female; Fibrinolysis; Hand; Humans; Male; Middle Aged; Prostaglandins F; Thrombophlebitis; Thromboxane B2; Thromboxanes; Veins

Topics: Aspirin; Graft Rejection; Humans; Kidney Transplantation; Thrombophlebitis; Thromboxane B2; Thromboxanes