6-ketoprostaglandin-f1-alpha and Blood-Coagulation-Disorders

Our previous study demonstrated the types of platelet dysfunction varied at early stage (∼3 h) in trauma-induced coagulopathy (TIC) caused by different types of injuries. And arachidonic acid (AA)-dependent pathway inhibition in platelet seemed to be specific for TIC caused by multiple injury (MI). The aim of this research was to further study AA-dependent pathway inhibition in platelets in a rat model of TIC caused by MI and to explore its potential mechanisms.. Sprague-Dawley rat model of TIC caused by MI was established. We used thrombelastography with platelet mapping as a measure of platelet function to assess the inhibitory extent of AA-dependent activation pathway. Flow cytometry was used to determine the expression of activation-dependent granular protein P-selectin (CD62P). In addition, the plasma levels of 6-Keto-prostaglandin F1 alpha (6-Keto-PGF1α), Prostaglandin E2, and Thromboxane B2 were assessed by enzyme-linked immuno sorbent assay.. The inhibition rate of AA-dependent pathway after injury was significantly higher than that of control. The maximum amplitude decreased in the MI group, compared with that of control. The percentage of CD62P expression in the MI group was remarkably lower than that of control after AA treatment. The plasma concentrations of 6-Keto-PGF1α and PGE2 increased in the MI group.. Platelets inhibition was observed in TIC caused by MI at early stage after injury, which might be partially attributed to AA-dependent activation pathway dysfunction. The increase of plasma Prostacyclin and PGE2 levels may contribute to the inhibition process.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Blood Coagulation Disorders; Blood Platelets; Dinoprostone; Disease Models, Animal; Epoprostenol; Male; Multiple Trauma; P-Selectin; Platelet Activation; Platelet Function Tests; Rats; Rats, Sprague-Dawley; Thrombelastography; Thromboxane B2

This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group), or burn injury combined with seawater immersion (BI group), or only immersion in seawater (I group), or control animals with no injury or immersion (C group). The circulating endothelial cell (CEC) count and coagulation-fibrinolysis parameters were measured. The CEC count in B group increased at 4 h, 7 h, and 10 h after injury and then reduced, whereas it continuously increased to a greater extent in BI group (P < 0.05). The von Willebrand factor (vWF) activity, plasminogen activator inhibitor (PAI-1), and the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1α (6-K-PGF1α ) in BI group had a marked increase after injury, and the tissue-type plasminogen activator (tPA) in the BI group decreased. Microscope observations revealed thrombus formation in lungs of the animals in BI group, but not in C, I, or B groups. Burn injury causes endothelial dysfunction, and seawater immersion lastingly aggravates this injury, leading to a higher risk of developing thrombosis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Coagulation; Blood Coagulation Disorders; Burns; Disease Models, Animal; Dogs; Endothelial Cells; Humans; Immersion; Lung; Plasminogen Activator Inhibitor 1; Seawater; Thromboxane B2; Tissue Plasminogen Activator; von Willebrand Factor

Effects of the effective components group of Xiaoshuantongluo formula (XECG) on rat acute blood stasis model were studied under the guidance of the concept of effective components group. Rat acute blood stasis model was induced by subcutaneous injection of epinephrine combined with ice water bath. Hemorheology indices such as whole blood viscosity, plasma viscosity, erythrocyte aggregation index and platelet aggregation rate; coagulation parameters including PT, APTT, TT and FIB; 6-keto-PGF1alpha, TXB2 and D-dimer levels were determined to evaluate the effects of XECG. The results showed that XECG significantly reduced ADP-induced platelet aggregation, but showed little influence on the whole blood viscosity, plasma viscosity and erythrocyte aggregation rate. XECG extended PT and TT slightly, but had no effects on APTT and FIB content. D-dimer levels significantly decreased after administration of XECG with a little decrease of TXB2, but the content of 6-keto-PGF1alpha did not change significantly. The results suggest that the role of XECG of anti-aggregation is more prominent.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Viscosity; Drug Combinations; Drugs, Chinese Herbal; Erythrocyte Aggregation; Fibrin Fibrinogen Degradation Products; Hemorheology; Male; Partial Thromboplastin Time; Plants, Medicinal; Platelet Aggregation; Prothrombin Time; Random Allocation; Rats; Rats, Sprague-Dawley; Thrombin Time; Thromboxane B2

We previously demonstrated that antithrombin III reduced the injury to endothelial cells caused by activated leukocytes in rats administered endotoxin. This occurred via the increase of the endothelial release of prostaglandin I2, which is a potent inhibitor of leukocyte activation. We evaluated the dose of antithrombin III required to prevent such endothelial cell injury in rats administered endotoxin, by comparing the effects of various antithrombin II doses on the pulmonary vascular injury. The intravenous administration of endotoxin, 5 mg/kg, produced a transient accumulation of leukocytes in the lung, followed by pulmonary vascular injury, as indicated by an increase in the pulmonary vascular permeability, and coagulation abnormalities. The dose of 250 U/kg significantly inhibited all such effects of endotoxin. While lower doses of antithrombin III (50 and 100 U/kg) significantly inhibited such coagulation abnormalities, they failed to prevent either the pulmonary accumulation of leukocytes or the subsequent pulmonary vascular injury. Rats administered endotoxin exhibited an accumulation of neutrophils and edematous changes in the pulmonary interstitial space. Although such changes were reduced after 250 U/kg of antithrombin III, they were unaffected by lower doses of 50 and 100 U/kg. Plasma levels of 6-keto-PGF1alpha were markedly increased in rats 90 min after the administration of endotoxin, and were significantly decreased in the endotoxin-treated rats administered the lower doses of antithrombin III (50 and 100 U/kg), but not altered in those endotoxin-treated rats receiving 250 U/kg of antithrombin III. These findings suggest that a higher antithrombin III dose is necessary to prevent endothelial cell injury than is required to inhibit coagulation abnormalities in an animal model of sepsis. These observations support the notion that antithrombin III may prevent endotoxin-induced endothelial cell injury by promoting endothelial release of prostaglandin I2 and thus inhibiting leukocyte activation.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antithrombin III; Blood Coagulation Disorders; Dose-Response Relationship, Drug; Endothelium, Vascular; Endotoxins; Lymphocyte Activation; Male; Pulmonary Circulation; Rats; Rats, Wistar; Respiratory Distress Syndrome; Sepsis

Acute respiratory distress syndrome (ARDS) adversely affects the outcome of patients with disseminated intravascular coagulation (DIC) associated with sepsis. To determine whether antithrombin III (AT III) is useful for the treatment of ARDS in sepsis, we evaluated the effect of AT III on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats. Although the intravenous administration of AT III (250 U/kg) prevented LPS-induced pulmonary accumulation of leukocytes, increases in pulmonary vascular permeability, and coagulation abnormalities, inactivated factor Xa, a selective inhibitor of thrombin generation, did not prevent such events other than the coagulation abnormalities. AT III promotes the endothelial release of prostacyclin by interacting with cell surface glycosaminoglycans in vivo. Trp49-modified AT III, which lacks affinity for heparin, did not prevent LPS-induced pulmonary vascular injury. Plasma levels of 6-keto-prostaglandin F1alpha were markedly increased in rats after the administration of LPS and significantly decreased in the LPS-treated rats administered Trp49-modified AT III, but not altered in those LPS-treated rats receiving AT III. Preventive effects of AT III were not observed in rats pretreated with indomethacin, which inhibits prostacyclin biosynthesis. Prostacyclin prevents LPS-induced pulmonary vascular injury by inhibiting leukocyte accumulation in the lungs. These observations strongly suggest that AT III prevents pulmonary vascular injury induced by LPS by promoting the endothelial release of prostacyclin, a potent inhibitor of leukocyte activation.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticoagulants; Antithrombin III; Blood Coagulation Disorders; Drug Evaluation, Preclinical; Endothelium, Vascular; Leukocyte Elastase; Leukocytes; Leukopenia; Lipopolysaccharides; Lung; Male; Mechlorethamine; Rats; Rats, Wistar; Serine Proteinase Inhibitors