thromboxane-b2 and Cerebrovascular-Disorders

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Circulation; Cerebrovascular Disorders; Coronary Disease; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Syndrome; Thrombosis; Thromboxane B2

Platelet aggregation was examined in 43 patients after ischemic stroke and in 16 healthy subjects using multiparametric aggregation index (MAI). The value of MAI was significantly higher in stroke patients (3.15 in patients and 0.92 l/mumol in controls, p < 0.0001). Patients who had increased MAI (n = 26) were treated with a daily dose of 100 mg acetilsalicylic acid (ASA). Platelet activity was measured before and on the 7th and 28th day of treatment measuring three parameters: MAI, spontaneous dysaggregation and collagen induced aggregation. All 3 methods showed a significant decrease in platelet aggregation on the 7th day of treatment, but further changes were not found on the 28th day. Serum levels of thromboxane-A2 (TXA2) and prostacycline (PGI2) metabolites (TXB2 and 6-keto-prostaglandin-F1 alpha) were determined before and on the 28th day of treatment. The effect of 100 mg ASA per day proved to be selective: comparing the serum levels before and after treatment, a significant decrease of TXB2 concentration was found without changes in the concentration of 6-keto-prostaglandin-F1 alpha. Evaluating MAI and the value of dysaggregation might reflect ineffectiveness of antiplatelet therapy in patients not responding to a daily dose of 100 mg of ASA. For these patients the increase of the daily dose of ASA, or changing to another antiplatelet drug might be recommended.

Topics: Aged; Aged, 80 and over; Aspirin; Blood Coagulation Tests; Brain Ischemia; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Prostaglandins F; Thromboxane A2; Thromboxane B2

To examine the antiplatelet effect of a novel pyrazolopyridine derivative (KC-764) in geriatric patients with ischemic stroke.. Randomized clinical trial of three graded dose levels.. A geriatric clinic attached to a nursing home.. Fifteen patients with a history of cerebral infarction with a mean age of 75 +/- 5 years (range, 65-83). Patients were divided into three groups and administered 10, 20, or 40 mg/day KC-764 for 8 weeks.. Platelet aggregation induced by arachidonate, ADP, collagen and platelet-activating factor. Plasma or serum levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha.. Platelet aggregation was inhibited by KC-764 administration and returned to the control level after discontinuation. Although plasma thromboxane B2 levels were markedly decreased, plasma 6-ketoprostaglandin F1 alpha was not affected. However, the dose of 10 mg/day was not sufficient to maintain an effective plasma level of KC-764. There were no side effects or changes in laboratory findings.. We confirmed that KC-764 at a dose of 20 to 40 mg/day is an effective antiplatelet agent and a good candidate for a trial to see if it is feasible for long-term use for the prevention of ischemic stroke in high-risk patients.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; Aged, 80 and over; Brain Ischemia; Bridged Bicyclo Compounds; Cerebrovascular Disorders; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Humans; Nicotinic Acids; Platelet Aggregation Inhibitors; Thromboxane B2

Cerebrovascular disease and other vascular diseases are common complications of non-insulin-dependent diabetes mellitus (NIDDM) and are associated with its increased morbidity and mortality. Platelet activation plays an important role in the pathomechanisms of these vascular diseases. Although several indices have been used to assess platelet activation, few data are available indicating which are more sensitive or more valuable in this situation. We have measured platelet arachidonic acid metabolites [thromboxane B2 (TXB2) and 11-dehydro-thromboxane B2 (TXB2)] and plasma P-selectin, platelet fibrinogen binding and membrane glycoproteins in 47 well-characterized NIDDM patients with cerebrovascular disease, 38 NIDDM patients without vascular diseases, and 36 age-matched healthy individuals. Our study shows that platelets were remarkably activated in NIDDM patients with cerebrovascular diseases. The measurement of plasma 11-dehydro-TXB2 and the determination of fibrinogen binding to, and P-selectin expression on platelets would reveal a higher diagnostic sensitivity for detecting in vivo platelet activation than other markers.

Topics: Adult; Aged; Arachidonic Acid; Biomarkers; Blood Platelets; Cerebrovascular Disorders; Diabetes Mellitus, Type 2; Humans; Middle Aged; P-Selectin; Platelet Activation; Platelet Glycoprotein GPIb-IX Complex; Platelet Glycoprotein GPIIb-IIIa Complex; Thromboxane B2

In order to delve into the mechanism governing the treatment of apoplexy by acupuncture at yangming channel points as main points, we observed the changes in the endothelin (ET) level in plasma, TXB2 and 6-Keto-PGF1 alpha levels in urine in convalescent apoplexy patients during acupuncture treatment. The results showed that the ET level in plasma in convalescent apoplexy patients was significantly higher than that in healthy subjects (P < 0.05), and the ET level in plasma in patients was decreased after one course of acupuncture treatment. It was found that before treatment the TXB2 level in urine in apoplexy patients was significantly higher than in healthy subjects, and the 6-Keto-PGF1 alpha level in urine in the patients was significantly lower than that in healthy subjects, with an increased ratio of TXB2 to 6-Keto-PGF1 alpha. After acupuncture treatment, the TXB2 level in urine was lowered with a decrease in the ratio of TXB2 to 6-Keto-PGF1 alpha. All this indicated that one of the mechanisms governing acupuncture treatment of apoplexy acupuncture at yangming channel points as main points was that acupuncture could produce therapeutic effects by adjusting the imbalance of important vaso-active substances, ET, TXA2, and PGI2.

Topics: 6-Ketoprostaglandin F1 alpha; Acupuncture Therapy; Adult; Aged; Cerebrovascular Disorders; Convalescence; Endothelins; Female; Humans; Male; Middle Aged; Thromboxane B2

The pathophysiologic sequence leading to respiratory failure after chest trauma can be an inevitable consequence of the primary injury or a secondary, mediator-driven inflammatory process. To distinguish between these alternatives, a simple cross-transfusion experiment was performed. A captive bolt gun injured the chest of anesthetized pigs that were mechanically ventilated with FiO2 = .21, .50, or .50 plus indomethacin (5 mg/kg intravenous; 15 min before injury). Tube thoracostomy immediately followed. After 30 min, blood from these injured donors was transfused into three matched groups of naive recipients (n = 8, 6, and 4, respectively) for a 33% exchange transfusion. Two control groups received blood from uninjured donors with tube thoracostomies only (FiO2 = .21, n = 7; FiO2 = .50, n = 10). Within 15-30 min after transfusion, in recipients from injured donors versus controls, lung compliance was decreased 20%, stroke volume and cardiac output were decreased 50%, and pulmonary vascular resistance was increased >300% (all p < .05). These changes recovered to baseline within 60-90 min. The stable metabolite of thromboxane A2, thromboxane B2, increased >500% in plasma within 15 min and remained elevated for >120 min. All responses were similar at 21 % or 50% O2, which suggests that hypoxia per se is not a cause of mediator production. All responses were eliminated by indomethacin. By 24 h, histologic changes included atelectasis in 3/3 recipients from injured donors versus 0/3 recipients from uninjured donors. We conclude that 1) blunt chest trauma releases blood borne mediators, including prostanoids; 2) these mediators can cause secondary cardiopulmonary changes in naive recipients similar to those produced by chest trauma; 3) the progression to trauma-induced respiratory failure is multifactorial; 4) early pharmacologic intervention, rather than supportive care alone, may benefit some victims of severe chest trauma.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Transfusion; Cerebrovascular Disorders; Contusions; Edema; Female; Hemodynamics; Indomethacin; Male; Oxygen Consumption; Pneumonia; Pulmonary Artery; Swine; Thoracic Injuries; Thromboxane B2; Vascular Resistance

Thromboxane B2, a stable metabolite of thromboxane A2, was studied in type 2 diabetic patients to evaluate the role played by prostaglandins in the onset of vascular complications.. The study was carried out in 30 subjects, 20 of whom were diabetics and 10 controls. Thromboxane B2 was assayed using the "Biotrak Thromboxane B2" kit.. In the first group of control subjects, the mean value of TXB2 was 6.39 +/- 0.89 pg/ml; in the second group, including diabetic patients without vascular complications, TXB2 levels were 8.89 +/- 1.51; in the third, consisting of diabetic patients with microangiopathy, the mean level was 46.28 +/- 6.82; in the fourth, including patients with micro- and macroangiopathy, the mean level was 98.78 +/- 17.15; the fifth group, with a mean value of 41.00 +/- 9.86, included diabetic patients with cerebral vasculopathy. Thromboxane B2 was correlated with glycemia but the results were not statistically significant (r = 0.28; p < 0.05). The correlation with the years since onset of diabetes was positive and statistically significant (r = 0.49; p < 0.05).. In conclusion, the authors emphasise that TXB2 is present in the circulation in diabetes in steadily increasing quantities over time since the onset of diabetes, leading to chronic vasoconstriction which in turn leads to a deterioration of vascular lesions in the districts where hypoglycemia has already caused the activation of neurotransmitter hormones with consequent slowing down of the blood flow and progressive tissue hypoxia.

Topics: Age of Onset; Blood Glucose; Cerebrovascular Disorders; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Middle Aged; Prostaglandins; Thromboxane A2; Thromboxane B2; Vasoconstriction

Both platelet activation and lipid peroxidation are potential sources of vasoactive eicosanoids that can be produced via the cyclooxygenase pathway, ie, thromboxane (TX) A2, or by free radical-catalyzed peroxidation of arachidonic acid, ie, isoprostanes. We investigated the biosynthesis of TXA2 and F2-isoprostanes, as reflected by the urinary excretion of 11-dehydro-TXB2 and 8-epi-prostaglandin (PG) F2 alpha respectively, in 62 consecutive patients (30 men, 32 women; mean age, 67 +/- 14 years) with acute ischemic stroke.. At least two consecutive 6-hour urine samples were obtained during the first 72 hours after onset of symptoms. Urinary eicosanoids were measured by previously described radioimmunoassays.. Repeated periods of enhanced thromboxane biosynthesis were found in 52% of patients. Urinary 11-dehydro-TXB2 averaged 221 +/- 207 (mean +/- SD; n = 197; range, 13 to 967) pmol/mmol creatinine in 30 patients treated with cyclooxygenase inhibitors (mostly aspirin) at the time of study versus 392 +/- 392 (n = 186; range, 26 to 2533) in 32 untreated patients (P < .001). The corresponding values for 8-epi-PGF2 alpha excretion were 74 +/- 42 (range, 14 to 206) and 83 +/- 65 (range, 24 to 570) pmol/mmol creatinine (P > .05). The correlation between the two metabolites was moderate in both untreated patients (r = .41, P < .001) and patients with cyclooxygenase inhibitors (r = .31, P < .001). In a multiple regression analysis, increased thromboxane production was independently associated with severity of stroke on admission, atrial fibrillation, and treatment with cyclooxygenase-inhibiting drugs.. We conclude that during the first few days after an acute ischemic stroke (1) platelet activation occurs repeatedly in a cyclooxygenase-dependent fashion; (2) platelet activation is not associated with concurrent changes in isoprostane biosynthesis; (3) platelet activation is independently associated with stroke severity and atrial fibrillation; and (4) isoprostane biosynthesis is largely independent of platelet cyclooxygenase activity.

Topics: Acute Disease; Aged; Atrial Fibrillation; Brain Ischemia; Cerebrovascular Disorders; Cyclooxygenase Inhibitors; Dinoprost; Female; Humans; Lipid Peroxides; Male; Middle Aged; Platelet Activation; Reference Values; Thromboxane B2

To investigate the effect of dietary eicosapentaenoic acid (EPA) on plasma lipoprotein levels, lecithin:cholesterol acyltransferase (LCAT) activity and liver acetyl CoA carboxylase activity, highly concentrated EPA (78%) purified from sardine oil was fed to stroke-prone spontaneously hypertensive rats (SHRSP) for 30 days. Significantly (P < 0.05) lower systolic blood pressure and plasma total cholesterol were observed in rats fed an EPA diet. In addition, higher HDL cholesterol and lower VLDL cholesterol levels were found in rats fed the EPA diet as compared with rats fed the control diet. However, no significant change of plasma LDL cholesterol was observed in rats between the two dietary groups. EPA supplementation increased the activity of plasma LCAT in rats. In addition, rats fed an EPA diet had lower liver total lipids and adipose tissue weights. However, higher liver acetyl CoA carboxylase activity was observed in rats fed the EPA diet. Results from the present study suggest that dietary EPA might stimulate the plasma lipoprotein metabolism and also alter lipogenesis in the liver of SHRSP rats.

Topics: Acetyl-CoA Carboxylase; Administration, Oral; Animal Feed; Animals; Cerebrovascular Disorders; Eicosapentaenoic Acid; Hypertension; Lipoproteins; Liver; Organ Size; Phosphatidylcholine-Sterol O-Acyltransferase; Rats; Rats, Inbred SHR; Thromboxane B2

Clinical and experimental studies suggest that platelets have a major role in the pathogenesis of cerebral ischemia. However, ex vivo both platelet aggregation studies and measurements of platelet-derived products in patients with cerebral ischemia have shown inconsistent results. The present study was designed to resolve this inconsistency.. We have measured the urinary excretion of a thromboxane metabolite, 11-dehydro-thromboxane B2, by a previously validated radioimmunoassay technique in 51 patients with acute cerebral ischemia who had experienced either a transient ischemic attack (14 patients) or an ischemic stroke (37 patients) and in 20 control patients with nonvascular neurological disorders. The median time between the onset of symptoms and urine sampling was 24 hours (range, from 2 hours to 8 days).. The excretion rate of immunoreactive 11-dehydro-thromboxane B2 ranged between 39 and 478 pmol/mmol creatinine in patients with a transient ischemic attack and between 23 and 5,916 pmol/mmol creatinine in stroke patients, with 29% (p = 0.18) and 51% (p = 0.004) of the urine samples, respectively, exceeding the upper limit of the control samples (251 pmol/mmol creatinine [mean +/- 2 SD]) (p = 0.01). In stroke patients, metabolite excretion was not related to the type (cortical or "lacunar") or site of cerebral infarction. Low-dose aspirin (50 mg per day for 7 days) reduced the urinary excretion by approximately 85% in 11 consecutive stroke patients.. We conclude that 1) episodes of enhanced thromboxane biosynthesis are detected infrequently in patients with a transient ischemic attack, 2) aspirin-suppressible episodes of increased thromboxane formation can be detected during the early phase of acute ischemic stroke, and 3) this finding may provide a rationale for testing the efficacy and safety of this drug in this setting.

Topics: Acute Disease; Aged; Aged, 80 and over; Blood Platelets; Brain Ischemia; Cerebrovascular Disorders; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Prospective Studies; Thromboxane B2

Acetylsalicylic acid (ASA) inhibits thromboxane production and hence platelet aggregation. However, individual variations in platelet aggregability and serum thromboxane B2 (TxB2) concentration after a low dose of ASA (40 mg/day) have been reported. To clarify this issue, we studied plasma thromboxane levels and platelet aggregation in 43 ischemic stroke patients. Of the 22 patients who received 100 mg of ASA daily, dissociation between inhibitory effects of ASA on the plasma TxB2 level and threshold concentrations of adenosine diphosphate was found in three cases after one month of drug administration, and in three cases after six, 12 and 18 months of ASA therapy. This dissociation also developed in two patients after one month and six months, respectively, of treatment in the 21 patients who received 300 mg of ASA daily. The dissociation between the inhibitory effects on plasma TxB2 and the circulating platelet aggregate ratio was found in two cases after taking medication for one month, and in four cases after six, 12, 18 and 24 months of therapy in the 100 mg ASA group. In the 300 mg ASA group, dissociation was noted in two cases after one month of medication, and in two cases after six and 12 months of medication. In these patients, although their TxB2 levels were inhibited to almost unmeasurable levels, platelet aggregation was still not inhibited. This ASA inhibitory dissociation phenomenon on platelet function may be due to the low dose of ASA, individual differences in platelet function in response to ASA therapy, or factors other than those involved in the cyclooxygenase system.

Topics: Aged; Aspirin; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Platelet Activation; Platelet Aggregation; Thromboxane B2

The purpose of this study was to compare the effects of low-to-high doses of aspirin on platelet aggregability determined by different methods and on the metabolism of thromboxane A2 and prostacyclin.. We administered increasing doses (40, 320, and 1,280 mg/day) of aspirin to 19 poststroke patients and studied the differences in 1) the changes in platelet aggregability depending on the methods of evaluation and 2) the concentrations of prostaglandin metabolites in the blood and urine.. Aggregation of platelet-rich plasma induced by a strong stimulus (10 microM ADP) was significantly reduced after 40 mg/day aspirin (p less than 0.005), and this reduction was similar to that after higher aspirin doses. In contrast, aggregation of platelet-rich plasma induced by weaker stimuli (1 and 5 microM ADP) decreased less significantly after 40 mg/day aspirin compared with that after higher aspirin doses. The serum thromboxane B2 generated after ex vivo incubation was reduced significantly (by 85%) after 40 mg/day aspirin and decreased further after 320 mg/day (by 96%) and 1,280 mg/day (by greater than 99%) of aspirin. The urinary 11-dehydro-thromboxane B2 concentration decreased less significantly after 40 mg/day aspirin (by 42%) compared with that after 320 mg/day (by 78%) and 1,280 mg/day (by 91%) aspirin doses. The urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha did not decrease after 40 mg/day aspirin but decreased significantly after higher doses of aspirin.. These findings suggest that different doses of aspirin may be necessary to prevent thrombogenesis induced by different triggers of different strengths and that 40 mg/day aspirin is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aspirin; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Epoprostenol; Female; Humans; Male; Middle Aged; Platelet Aggregation; Thromboxane A2; Thromboxane B2

We reported previously that stroke risk factors prepared the brain stem for the development of ischemia and hemorrhage and induced the production of tumor necrosis factor following an intrathecal injection of lipopolysaccharide, a prototypic monocyte-activating stimulus. This study evaluates whether blood or brain cells of hypertensive rats produce more proinflammatory and prothrombotic mediators than do blood or brain cells of normotensive rats.. Levels of tumor necrosis factor, platelet-activating factor, 6-ketoprostaglandin F1 alpha, and thromboxane B2 in the cerebrospinal fluid and blood of spontaneously hypertensive and normotensive Wistar-Kyoto rats were monitored before and after a challenge with lipopolysaccharide.. Little or no activity from these mediators was found in the cerebrospinal fluid or blood of saline-injected control animals. Intravenous administration of lipopolysaccharide (0.001, 0.1, and 1.8 mg/kg) produced dose-dependent increases in blood levels of all mediators in hypertensive rats. In normotensive rats the levels were less than in hypertensive rats and were not clearly dose-related. When lipopolysaccharide was injected intracerebroventricularly, more tumor necrosis factor was measured in the cerebrospinal fluid than in the blood, suggesting local synthesis of this cytokine. Levels of tumor necrosis factor and platelet-activating factor in the cerebrospinal fluid were higher in hypertensive than in normotensive rats. The thromboxane A2/prostacyclin ratio was not altered significantly between the two rat strains.. It is suggested that the higher incidence of brain stem ischemia and hemorrhage after the intrathecal injection of lipopolysaccharide in hypertensive rats than in normotensive rats might be related to the higher levels of the two cytotoxic factors tumor necrosis factor and platelet-activating factor produced in response to such challenge.

Topics: Animals; Brain; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Hypertension; Injections, Intravenous; Injections, Intraventricular; Leukocyte Count; Lipopolysaccharides; Platelet Activating Factor; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reference Values; Risk Factors; Thromboxane B2; Tumor Necrosis Factor-alpha

Thromboxane B2 (TXB2) levels in bleeding time blood and in serum were measured in 13 elderly patients with cardiovascular disease, seven of whom were receiving continuous treatment with low dose acetylsalicylic acid (ASA, 125 mg every second day--250 mg daily) for prevention of stroke. Blood sampling was performed openly, but assays of TXB2 were performed by a blinded investigator. In patients treated with ASA, median serum TXB2-levels were 4% and TXB2-levels in bleeding-time blood were less than 16% of the corresponding levels in patients without ASA (P less than 0.01). The results show that in elderly atherosclerotic patients very low doses of ASA substantially suppress TXB2 formation, not only in serum but also at the site of local haemostasis. The extent of suppression is comparable to that previously reported from young healthy subjects.

Topics: Aged; Aged, 80 and over; Aspirin; Bleeding Time; Cardiovascular Diseases; Cerebrovascular Disorders; Hemostasis; Humans; Thromboxane B2

Topics: Adenosine Diphosphate; Aged; Aspirin; Brain Ischemia; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Platelet Aggregation; Random Allocation; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Dinoprostone; Female; Heart Diseases; Humans; Male; Middle Aged; Radioimmunoassay; SRS-A; Thromboxane B2

Topics: Animals; Cerebrovascular Disorders; Disease Models, Animal; Edema; Ischemia; Male; Motor Activity; Prostaglandins; Rabbits; Reperfusion; Spinal Cord; Thromboxane B2

The relation of brain eicosanoids to progression of cerebral edema was studied in stroke-resistant spontaneously hypertensive rats subjected to incomplete global brain ischemia induced by bilateral occlusion of the common carotid arteries. Thromboxane B2 and 6-keto prostaglandin F1 alpha levels were significantly elevated 5 minutes after reperfusion but returned to control levels by 30 minutes. In contrast, leukotriene C4 levels increased 2 hours after bilateral common carotid artery occlusion and peaked 30 minutes after reperfusion, with higher levels persisting until 60 minutes after reperfusion. Cerebral ischemia was accompanied by cerebral edema early after reperfusion. The edema correlated with increased leukotriene C4 levels. That the increased brain water content was causally related to an increase in leukotriene C4 was supported by results obtained following administration of the 5-lipoxygenase inhibitors ONO-LP-016 and AA-861. Both inhibitors suppressed the increased leukotriene C4 and brain water contents after reperfusion. Our results indicate that leukotriene C4 is closely associated with an induction of ischemic cerebral edema.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Benzoquinones; Body Water; Brain; Brain Edema; Cerebrovascular Circulation; Cerebrovascular Disorders; Disease Susceptibility; Eicosanoic Acids; Hypertension; Male; Quinones; Rats; Rats, Inbred SHR; SRS-A; Thromboxane B2

The purpose of our study was to investigate the effects of different doses of acetylsalicylic acid on platelet aggregation. Among inpatients of the National Taiwan University Hospital, 236 cases of completed stroke and seven cases of reversible ischemic neurologic deficit that were diagnosed by computed tomography of the brain and that had not ingested acetylsalicylic acid or acetylsalicylic acidlike drugs for greater than 2 weeks before admission were selected for this study. Thromboxane B2 and 6-keto-PGF1 alpha were measured by radioimmunoassay, threshold concentration of adenosine diphosphate was measured by Born's method, and circulating platelet aggregates were measured by the method of Wu and Hoak. Various single doses of acetylsalicylic acid (75, 300, or 600 mg) or 300 mg acetylsalicylic acid every 6 hours for four doses or one dose of 300 mg acetylsalicylic acid with 75 mg dipyridamole significantly suppressed the mean plasma thromboxane B2 concentrations and elevated the mean adenosine diphosphate threshold concentrations. Abnormal plasma thromboxane B2 concentrations, adenosine diphosphate threshold concentrations, or circulating platelet aggregate ratios were significantly normalized after administration of these regimens. The effects were not significantly different among treatment groups. Forty milligrams of acetylsalicylic acid seemed to have less platelet-inhibitory effect. A single dose of 75 mg acetylsalicylic acid significantly inhibited platelet hyperfunction and effectively corrected the abnormal plasma thromboxane B2 concentrations, adenosine diphosphate threshold concentrations, and circulating platelet aggregate ratios. Higher doses did not enhance the inhibitory effect. In addition, this single dose of acetylsalicylic acid did not significantly suppress plasma 6-keto-PGF1 alpha. We conclude that 75 mg acetylsalicylic acid per day is adequate to inhibit platelet hyperfunction.

Topics: Adenosine Diphosphate; Aged; Aged, 80 and over; Aspirin; Blood Platelets; Cerebrovascular Disorders; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation; Thromboxane B2

The effects of low daily oral doses of aspirin (40 mg/day) on platelet aggregability and serum thromboxane B2 concentrations were studied in 19 poststroke patients. Although platelet aggregation was reduced significantly after 1 week, there was wide individual variation in the inhibition of platelet function in spite of marked decreases of serum thromboxane B2 concentrations by greater than 90% (from 224 +/- 58 to 8 +/- 8 ng/ml). There was no correlation between collagen-induced platelet aggregability and serum thromboxane B2 concentration before aspirin administration in the range 100-350 ng/ml, but after 1 week of repeated administration of aspirin, there was a correlation between platelet aggregability and serum thromboxane B2 concentrations of less than 25 ng/ml (r = 0.68, p less than 0.01). However, platelet inhibition was insufficient even in some patients with markedly decreased thromboxane B2 concentrations (less than 5 ng/ml). Our results suggest that individual variation of platelet aggregability in response to low-dose aspirin may be due to variation not only in the degree of inhibition of thromboxane A2 production but also in the relative dependence of platelet aggregation on extra-arachidonic pathways.

Topics: Aged; Aged, 80 and over; Aspirin; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Platelet Aggregation; Thromboxane B2

Thromboxane A2 is a prostanoid having potent platelet aggregatory and vasoconstrictor properties. To determine a possible role for thromboxane A2 in the development of severe hypertension and stroke, we chronically administered the selective thromboxane A2 synthase inhibitor UK-38,485 (Dazmegrel) to stroke-prone spontaneously hypertensive rats (SHRSP). Serum thromboxane B2 (the stable hydrolysis product of thromboxane A2) generation was significantly greater in incubates of whole blood from SHRSP than in those from normotensive control Wistar-Kyoto rats and was inhibited greater than 89% by UK-38,485 administered in vivo. In 10 male SHRSP fed a Japanese-style rat chow and given 1% NaCl in drinking water to accelerate the occurrence of stroke, treatment with 100 mg/kg/day UK-38,485 by gavage starting at 8.6 weeks of age diminished systolic blood pressure elevation at 10 (205 +/- 2 vs. 220 +/- 4 mm Hg, p less than 0.01) and 11 weeks of age (210 +/- 4 vs. 239 +/- 7 mm Hg, p less than 0.01) compared with 10 untreated SHRSP. The ultimate establishment of severe hypertension was not prevented by UK-38,485. Stroke-related mortality was 70% in both UK-38,485-treated and control SHRSP at 14 weeks of age. Histologic examination revealed cerebrovascular lesions consistent with the occurrence of stroke in both control and UK-38,485-treated SHRSP. Our results support a possible role for thromboxane A2 in the elevation of blood pressure in SHRSP but do not support a possible role for the prevention of stroke by thromboxane A2 synthase inhibition in these rats.

Topics: Animals; Blood Pressure; Brain; Cerebrovascular Disorders; Disease Susceptibility; Hypertension; Imidazoles; Male; Osmolar Concentration; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Thromboxane A2; Thromboxane B2

A thrombo-embolic stroke model was produced by the internal carotid artery (ICA) infusion of arachidonic acid (AA). The differences in responses to AA ICA infusion were investigated in stroke-resistant spontaneously hypertensive rats (SHRSR) and Wistar-Kyoto (WKY) rats. The SHRSR showed a higher mortality, more severe brain oedema and brain metabolic impairment, more prominent elevation of TXB2 and 6-keto-PGF1 alpha. Electron microscopic observation revealed more severe endothelial damage, mitochondrial swelling and perivascular oedema and earlier thrombus formation in SHRSR than in WKY rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Brain; Brain Ischemia; Cerebrovascular Disorders; Hypertension; Male; Microscopy, Electron, Scanning; Rats; Rats, Inbred Strains; Thromboxane B2

Topics: Acute Disease; Adult; Aged; Cerebral Hemorrhage; Cerebrovascular Disorders; Female; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Prognosis; Radioimmunoassay; Thromboxane B2

Bleeding time, thromboxane production and inhibition of platelet aggregation were studied before and during administration of acetylsalicylic acid in doses of 50, 100, 325 an 1000 mg daily in eighteen patients with cerebrovascular disease. Inhibition of thromboxane production and platelet aggregation was almost complete at 50 mg acetylsalicylic acid daily, and median bleeding time had increased significantly from 5.5 to 6.5 min at this dose and reached a maximum of 7.5 min at 100 mg daily. Further increase of the dose resulted in a slight decrease in bleeding time. It appears that a strong effect on platelet function can be achieved by small doses of acetylsalicylic acid, and that higher doses might be less effective.

Topics: Adult; Aged; Aspirin; Bleeding Time; Brain Ischemia; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Male; Middle Aged; Platelet Aggregation; Thrombosis; Thromboxane B2

Topics: Aged; Aged, 80 and over; Aspirin; Bleeding Time; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Thromboxane B2

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: Adolescent; Adult; Aged; Arteries; Aspirin; Cerebrovascular Disorders; Female; Humans; Hypertension; Jugular Veins; Male; Middle Aged; Thromboxane B2; Thromboxanes; Veins

A basic study was conducted on the method for the determination of thiobarbituric acid-reactive substances (TBARS) produced by platelets. Some modifications were introduced which enabled a precise semimicrodetermination. The average values of platelet TBARS production in hypertensives and in patients with cerebral infarction were higher than that in healthy controls. Among patients with cerebral infarction, those with angiographically demonstrated obstruction of internal carotid or middle cerebral arteries showed an increased production as compared with non-obstructive cases, these results may suggest the important role of platelet arachidonate metabolism in obstructive cerebrovascular disorders.

Topics: Aged; Arachidonic Acids; Blood Platelets; Cerebrovascular Disorders; Female; Humans; Hypertension; Lipids; Male; Malonates; Malondialdehyde; Middle Aged; Thromboxane B2

Endogenous biosynthetic capacities for prostaglandin (PG)E2, thromboxane (TX)B2 (a stable degradation product of TXA2) and 6 keto-PGF1 alpha (a stable degradation product of PGI2) in the brain-stem fractions of stroke-resistant spontaneously hypertensive rats (SHRSR) and control Wistar-Kyoto rats (WKR) were determined with novel methods and presented in an original report. In comparison with WKR, it is characteristically found that TXB2 synthesis is increased in excess of threefold in the pons-medulla oblongata of SHRSR, while being decreased by 75% in the hypothalamic region of SHRSR (0.01 less than p less than 0.05). On the other hand, the biosynthesis of PGE2 is adaptively elevated in both hypothalamus and pons-medulla oblongata regions of each animal, although the PGI2/PGE2 ratio was lowered in both these regions of SHRSR.

Topics: Animals; Brain Stem; Cerebrovascular Disorders; Hypertension; Male; Prostaglandins E; Prostaglandins F; Rats; Thromboxane B2; Thromboxanes

The ability of platelets to synthesize thromboxane B2 (TxB2) from arachidonic acid (AA) or prostaglandin H2 (PGH2) was studied in 26 control subjects, 40 patients with essential hypertension, 20 patients with cerebrovascular disease (CVD) not taking aspirin and 11 patients with CVD taking aspirin. The activity of platelets to form TxB2 from AA or PGH2 was measured using 1-14C arachidonic acid or 1-14C PGH2 as a substrate. There was no significant difference in TxB2 generation from AA or PGH2 among the platelets collected from the control subjects, hypertensive patients and CVD patients not taking aspirin. In CVD patients taking aspirin, marked suppression was observed in TxB2 synthesis from AA, but no suppression in TxB2 synthesis from PGH2. At least 750 mg aspirin per day were required for nearly complete suppression of TxB2 generation from AA.

Topics: Adolescent; Adult; Aged; Arachidonic Acids; Aspirin; Blood Platelets; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Female; Humans; Hypertension; Male; Middle Aged; Prostaglandins H; Thromboxane B2; Thromboxanes