Aspirin resistance defined by light transmittance aggregometry (LTA) or urinary 11-dehydro-thromboxane B2 has been associated with an increased risk of adverse clinical events. However, aspirin resistance based on the point-of-care VerifyNow-Aspirin assay (aspirin reaction unit > or = 550) shows poor sensitivity compared with LTA. In aspirin-treated patients, activation by cyclooxygenase- independent pathways may be associated with residual platelet reactivity, which may cause adverse clinical outcomes in some portion. A large-scale, prospective study using several platelet function assays should be performed to establish the long-term clinical significance of antiplatelet resistance in Korean patients treated with coronary stenting. Accordingly, we can apply tailored antiplatelet therapy in resistant patients.
Aspirin ; Blood Platelets ; Humans ; Light ; Prospective Studies ; Stents ; Thromboxane B2

The inhibitory effects of perilla oil on the platelet aggregation in vitro and thrombosis in vivo were investigated in comparison with aspirin, a well-known blood flow enhancer. Rabbit platelet-rich plasma was incubated with perilla oil and aggregation inducers collagen or thrombin, and the platelet aggregation rate was analyzed. Perilla oil significantly inhibited both the collagen- and thrombin-induced platelet aggregations, in which the thromboxane B2 formation from collagen-activated platelets were reduced in a concentration-dependent manner. Rats were administered once daily by gavage with perilla oil for 1 week, carotid arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Perilla oil delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 0.5 mL/kg. In addition, a high dose (2 mL/kg) of perilla oil greatly prevented the occlusion, comparable to the effect of aspirin (30 mg/kg). The results indicate that perilla oil inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is proposed that perilla oil could be a good candidate without adverse effects for the improvement of blood flow.
Animals ; Aspirin ; Blood Platelets* ; Collagen ; Perilla* ; Platelet Aggregation* ; Platelet-Rich Plasma ; Rats ; Thrombin ; Thrombosis* ; Thromboxane B2

OBJECTIVE: To investigate the antithrombotic effects of recombinant hirudin and its mechanism. METHODS: Sixty male Kunming mice were randomly divided into 6 group (=10):control group, model group, aspirin (25 mg/kg) group, recombinant hirudinlow, middle and high dose (0.05, 0.1, 0.2 mg/kg) groups.Except mice in control group, 2.5 mg/kg carrageenan was injected intraperitoneallyto mice in the other groups to produce thrombosis on the mice tail. The mice in aspirin group were administrated intraperitoneally 25 mg/kg aspirin, the mice in recombinant hirudinlow, middle and high dose groups were administrated intraperitoneally 0.05, 0.1, 0.2 mg/kg combinanthirudin, the mice in control group and model group were administrated intraperitoneallynormal saline at the same volume respectively at 24 h, 0.5 h before injecting carrageenan and 24 h after injecting carrageenan. The black tail length of mice and the incidence of black tail were observed at 48h after injection of carrageenan; prothrombin time (PT), activated partial thromboplastin time (APTT), tissue plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1), 6-keto-PGF1α, and thromboxane B2 (TXB2) level in mice plasma were determined. RESULTS: As compared with control group, the mice in model group presented tail thrombosis; PT level in plasma was significantly shortened (<0.01), PAI-1 and TXB2levels in plasma were significantly increased (<0.01), while the t-PA and 6-keto-PGF1α levels in plasma in model group were significantly decreased (<0.01). As compared with model group, the thrombus length in the tail was significantly shortened (<0.05, <0.01), PT level was obviously prolonged (<0.01), and the plasma levels of PAI-1 and TXB2 were significantly decreased (<0.01), while the plasma levels of t-PA and 6-keto-PGF1α were significantly increased (<0.01)in the mice of recombinant hirudin low dose, middle dose, high dose groups and aspirin group. As compared with aspirin group, the thrombus length in the tail was significantly increased (<0.05), PT level was obviously shortened (<0.01), and the plasma levels of PAI-1 and TXB2 were significantly increased (<0.01)in the mice of recombinant hirudin low dose group; the plasma level of 6-keto-PGF1α was significantly decreased (<0.01, <0.05) in the mice of recombinant hirudin low dose and middle dose groups; the plasma levels of PAI-1 and TXB2 were significantly increased (<0.01, <0.05)in the mice of recombinant hirudin middle dose group. CONCLUSIONS The recombinant hirudin can fight against thrombosis, its antithrombotic mechanisms may be related to its influence on the exogenous coagulation system and the promotion of fibrinolysis function.
Animals ; Blood Coagulation ; Fibrinolytic Agents ; Hirudins ; pharmacology ; Male ; Mice ; Recombinant Proteins ; Thromboxane B2 ; Tissue Plasminogen Activator

OBJECTIVETo investigate the dynamic changes of plasma levels of prostacycline (PGI2) and thromboxane A2 (TXA2) and their relationship with the severity of hepatic injury in rats with nonalcoholic fatty liver disease (NAFLD).

METHODSWe established a NAFLD model, with a fat-rich diet consisting of 10% lard oil + 2% cholesterol, which was given to Sprague-Dawley rats (n=48) for a period of 8, 12, 16 and 24 weeks. The other rats were fed standard diets and were used as normal controls (n=24). At sacrifice, liver pathology scores were evaluated and plasma levels of PGI2, its stable metabolic product 6-keto-PGF1 alpha and TXA2, and TXB2 were determined by radioimmunoassay.

RESULTSSimple fatty livers were observed in the model group at 8 weeks. From 12 weeks to 24 weeks, the livers gradually progressed from simple steatohepatitis to liver fibrosis. Plasma levels of TXB2 in the model group increased higher than in the control group after 8 weeks [(52.4+/-3.15) ng/L vs (41.1+/-1.45) ng/L] and continued to increase over time, with the highest levels at 24 weeks [(117.7+/-7.47) ng/L]. A strong positive correlation (r=0.537) was seen between plasma TXB2 levels and the severity of liver injury. Plasma 6-keto-PGF1 alpha concentrations decreased in the model group in comparison with the control group after 8 weeks [(31.1+/-1.62) ng/L vs (36.5+/-1.68) ng/L] and continued to decrease over time, with the lowest concentrations at 24 weeks [(3.4+/-2.43) ng/L t=3.77]. A negative correlation was shown between the 6-keto-PGF1 alpha level and the severity of the liver injury.

CONCLUSIONA rat model of NAFLD was established successfully by feeding a fat-rich diet for 24 weeks. In this model, the imbalance of plasma PGI2 and TXA2 levels (increased TXB2 and decreased 6-keto-PGF1 alpha levels) may play a role in the pathogenesis of experimental NAFLD.

6-Ketoprostaglandin F1 alpha ; blood ; Animals ; Epoprostenol ; blood ; Fatty Liver ; blood ; Liver ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Thromboxane A2 ; blood ; Thromboxane B2 ; blood

OBJECTIVETo study thrombosis and its significance after acute experimental pulmonary thromboembolism.

METHODSThe acute pulmonary thromboembolism (PTE) model of rabbits was established by intravenous injection of autologous blood clots (0.04 g/kg) which were stabilized in temperature-controlled (70 degrees C) distilled water for 10 min. The process of thrombosis was observed grossly and microscopically. The Quick's method was used to examine the coagulability of blood and radioimmunoassay was employed to measure the level of plasma thromboxane A(2) and endothelin.

RESULTSThrombotic propensity was observed at 1 h, fresh thrombus started to form and the blood coagulation system was activated at 24 h following clots infusion. Emboli were completely or partly dissolved at 5 d and appeared to organize at both 10 d and 14 d after clots were infused. Venous plasma thromboxane A(2) concentration began to increase at 5 min (2489.59 +/- 714.68 ng/L) and reached its maximum at 15 min (2545.46 +/- 590.58 ng/L) then declined at 60 min after clot infusion (P < 0.001, respectively, vs 626.59 +/- 510.02 ng/L of pre-clot). The level of endothelin in both arterial and venous blood increased at 5 d post-clot infusion (840.74 +/- 154.19 ng/L, 230.35 +/- 52.39 ng/L, respectively) compared to the one before infusion (602.66 +/- 453.26 ng/L, 148.01 +/- 53.28 ng/L, respectively, P < 0.05).

CONCLUSIONSThrombosis occurs after autologous-blood-clot-induced PTE. The interactions between thrombus formation, fibrinolysis and organization determines the consequences of emboli. Abnormalities of endothelin metabolism and the increment of thromboxane A(2) may play an important role in PTE.

Animals ; Blood Coagulation ; Endothelins ; blood ; Lung ; pathology ; Pulmonary Embolism ; blood ; pathology ; Rabbits ; Thrombosis ; pathology ; Thromboxane B2 ; blood

In order to find out the relationship between arachidonic acid(AA) metabolites and the development of vasospasm following a subarachnoid hemorrhage(SAH), we evaluated the cerebrospinal fluid(CSF) levels of the two main AA metabolites, prostacyclin(PGI2) and thromboxane A2(TXAZ) by measuring their stable degredation products 6-keto-prostaglandin F1alpha(PGF1) and thromboxane B2(TXB2) using radioimmunoassay methods in 32 patients after an aneurysmal rupture and in 11 patients without an aneurysmal rupture as a control group. We compared the data between aneurysmal ruptured patients and control group patients. We also divided the data of the aneurysmal ruptured patients into 3 groups checking them between 1-4, 5-11, and 12-28 days after the SAH, and compared the data among the groups, then the data was also compared between non-vasospasm and clinical or severe angiographic vasospasm groups of patients. The results showed that the AA metabolism was enhanced after the SAH, The TXB2 increased the greatest amount in 1-4 days after the SAH and significantly decreased statistically 12 days after the SAH(p<0.002). This study also showed that the TXB2 level was significantly higher statistically in 1 to 4 days in the clinical or angiogrophically severe vasospasm group than in the non-vasospasm group of patients(p<0.032). PGF1 did not show any statistically significant changes according to the number of SAH days or a difference between the vasospasm and non-vasospasm groups. This result suggests if the AA metabolites are involved in the pathogenesis of cerebral vasospasm, and the lumbar CSF levels of AA metabolites in aneurysmal patients reflect the arterial synthesis of PGI2 and platelet origin of TXA2, the elevation of TXA2 or other vasoconstrictor prostaglandins is more likely to play a major role in the pathogenesis of vasospasm than PGI2 deficiency. The measurements of the CSF TXB2 in 1 to 4 days after a SAH may have an expectant value in the development of clinical or severe angiographic vasospasm(exclude the accompanying intraventricular hemorrhage patients).
Aneurysm* ; Arachidonic Acid ; Blood Platelets ; Cerebrospinal Fluid* ; Epoprostenol ; Hemorrhage ; Humans ; Metabolism ; Prostaglandins I ; Radioimmunoassay ; Rupture ; Subarachnoid Hemorrhage* ; Thromboxane A2 ; Thromboxane B2* ; Vasospasm, Intracranial

The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-dependent manner. Rats were orally administered with nattokinase for 1 week, and their carotid arteries were exposed. Arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Nattokinase delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 160 mg/kg. In addition, a high dose (500 mg/kg) of nattokinase fully prevented the occlusion, as achieved with aspirin (30 mg/kg). The results indicate that nattokinase extracted from fermented soybean inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is suggested that nattokinase could be a good candidate without adverse effects for the improvement of blood flow.
Animals ; Aspirin ; Blood Platelets* ; Carotid Arteries ; Collagen ; Platelet Aggregation* ; Platelet-Rich Plasma ; Rats ; Soybeans ; Thrombin ; Thrombosis* ; Thromboxane B2

Animals ; Calcitonin Gene-Related Peptide ; blood ; Cerebral Infarction ; blood ; Endothelins ; blood ; Humans ; Nitric Oxide ; blood ; Plasminogen Inactivators ; blood ; Thromboxane B2 ; blood

OBJECTIVETo study the changes of cardiovascular regulating factors in rats during recovery of aerobic exhaustive exercise.

METHODSSixty male Wistar rats were randomly divided into control group, 1 h-exercise group, 3 h-exercise group, exhausted group, 2 h-recovery group and 12 h-recovery group. The rats were killed at corresponding times for each group after an 8-week-long treadmill training, and the levels of NO, ET, ANP and TXB2 in plasma were measured in each group.

RESULTSNO/ET ratio of 1 h-exercise group was significantly higher than that in control group (P < 0.01), while it was significantly decreased in 3 h-exercise group and exhausted group (P < 0.05). ANP contents in rat plasma were significantly higher in 3 h-exercise group, exhausted group and 2 h-recovery group than that in control group (P < 0.05 or P < 0.01). The concentration of TXB2 in plasma was significantly increased in 3 h-exercise group, exhausted group and 2 h-recovery group (P < 0.05).

CONCLUSIONChanges in cardiovascular regulating factors after exhaustive exercise may lead to deficiency of coronary circulation blood/oxygen supply, which may cause exercise-induced fatigue.

Animals ; Atrial Natriuretic Factor ; blood ; Cardiovascular System ; physiopathology ; Endothelins ; blood ; Exercise Test ; Fatigue ; blood ; Male ; Nitric Oxide ; blood ; Physical Conditioning, Animal ; Rats ; Rats, Wistar ; Thromboxane B2 ; blood

OBJECTIVETo explore the changes of the neurotransmitters in patients with chronic pulmonary heart disease (CPHD) and its clinical significance.

METHODSSeventy-two patients with CPHD (42 males, 30 females, mean age 55.6-/+8.9 years) were enrolled in the study, including 48 patients with compensated CPHD and 24 with uncompensated CPHD. Plasma endothelin (ET), thromboxance B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-K-PGFlalpha) were detected by radioimmunoassay. Thirty blood donors were selected as the normal control.

RESULTSCompared with the normal controls, CPHD patients showed abnormal pulmonary function, and significantly elevated levels of plasma ET and TXB2 (P<0.01) and lowered 6-K-PGFlalpha(P<0.01), but no significant differences were found between the patients with compensated CPHD and uncompensated CPHD (P>0.05). Plasma ET and TXB2 levels were inversely correlated to 6-K-PGFlalpha level (r=-0.4571, P<0.05).

CONCLUSIONThe patients with CPHD present with obvious changes of plasma ET, TXB2 and 6-K-PGFlalpha.

6-Ketoprostaglandin F1 alpha ; blood ; Adult ; Case-Control Studies ; Chronic Disease ; Endothelins ; blood ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Heart Disease ; blood ; Thromboxane B2 ; blood