thromboxane-b2 and anisodamine

Thromboxane (TXA2) and prostacyclin (PGI2) levels, circulatory platelet aggregate ratios (CPAR), CPK, LDH, GOT, platelet counts, blood viscosity, cortisol and urine epinephrine contents were determined in 42 burned patients who were divided into two groups: Group I control (n = 34) and Group II (n = 8) treated with TXA2 synthesis inhibitor, anisodamine. It was found that in controls, both TXA2 and the TXA2/PGI2 ratio increased significantly. There was no marked difference in PGI2 levels between the two groups. Platelet counts and CPAR decreased, while blood viscosity, CPK, LDH, GOT, cortisol and epinephrine in the controls were all significantly higher than those found in Group II patients. All these findings suggested that the changes of TXA2 and the TXA2/PGI2 ratios played an important role in the haemodynamics and haemorrheology in burn shock. The TXA2 synthesis inhibitor, anisodamine, showed beneficial effects by restoring the haemodynamic and rheological disturbances towards normal by virtue of their ability to induce vascular constriction, platelet aggregation, cellular destruction, destabilization of membranes and release of chemical mediators (including enzymes). Furthermore, at 1-3 days postburn, the levels of CPK, LDH and GOT in controls were higher than those measured at 12 h postburn, but this phenomenon was not marked in the treated group, suggesting that after resuscitation, reperfusion damage had occurred and TXA2 might be responsible for the damage. It is assumed that anisodamine could protect tissues from reperfusion damage. The findings also suggested that anisodamine could quicken the restoration of neuroendocrine disturbance initiated by shock (stress).

Topics: Adolescent; Adult; Aspartate Aminotransferases; Burns; Creatine Kinase; Epinephrine; Female; Humans; Hydrocortisone; Infusions, Intravenous; L-Lactate Dehydrogenase; Male; Middle Aged; Shock; Solanaceous Alkaloids; Thromboxane A2; Thromboxane B2; Vasodilator Agents

The changes of contents of TXB2 and 6-Keto-PGF1a were studied in severely acute hypoxic cultured intra-pulmonary arteriolar smooth muscle cells (PASMCs) under the action of anisodamine. The results demonstrated that the contents of TXB2 and 6-Keto-PGF1a and their ratio were significantly increased in severe acute hypoxic PASMCs' medium. The content of TXB2 decreased significantly, but the content of 6-Keto-PGF1a was hardly affected by anisodamine under normoxia and hypoxia. These findings suggest that acute and severe hypoxia results in pulmonary vascular constriction through increased production of PASMCs and liberation of TXA2, or PGI2, and increased TXA2/PGI2 ratio. The latter effect of hypoxia could be prevented by anisodamine, which antagonized the effect of hypoxia induced pulmonary vasoconstriction.

Topics: Animals; Arterioles; Cell Hypoxia; Cells, Cultured; Epoprostenol; Lung; Muscle, Smooth, Vascular; Rabbits; Solanaceous Alkaloids; Thromboxane B2; Vasodilator Agents

The parasympathetic nervous system actively participates in the regulation of pathophysiologic responses in circulatory shock. To determine the effects of cholinergic blockade in endotoxic shock in newborn piglets, 16 chronically instrumented newborn piglets were infused with 10 mg/kg of endotoxin over 10 min. Eight animals were injected intravenously with 10 mg/kg of anisodamine, an anticholinergic drug, 10 min before endotoxin and then with escalating doses of 2, 5, 10, and 20 mg/kg every 10 min, beginning 60 min after endotoxin. The other eight animals were given saline as a control. Endotoxin infusion caused elevations in mean pulmonary artery pressure and vascular resistance index and an initial increase in systemic artery pressure followed by hypotension. Heart rate was stable for 45 min and then increased. Cardiac index fell from a baseline of 173 +/- 20 (mean +/- S.E.) to 136 +/- 23 mL.min-1.kg-1 60 min after endotoxin. Pretreatment with anisodamine increased heart rate from 163 +/- 15 to 289 +/- 10 beats.min-1 and cardiac index from 195 +/- 15 to 238 +/- 14 mL.min-1.kg-1 before endotoxin infusion. These variables remained at higher levels than in the control group until 60 min after endotoxin infusion; thereafter, the two groups were similar. The changes in pulmonary and systemic artery pressures were not significantly altered by anisodamine. After 60 min, additional doses of anisodamine caused no significant hemodynamic responses, and the differences between the two groups were not significant. Arterial plasma thromboxane B2 levels rose immediately and tumor necrosis factor-alpha levels increased 60 min after endotoxin infusion; no significant differences were noted between groups at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Animals, Newborn; Blood Pressure; Carbon Dioxide; Cardiac Output; Diarrhea; Digestive System; Dose-Response Relationship, Drug; Endotoxins; Female; Heart Rate; Hemodynamics; Oxygen; Parasympatholytics; Partial Pressure; Pulmonary Artery; Shock, Septic; Solanaceous Alkaloids; Stroke Volume; Swine; Thromboxane B2; Time Factors; Tumor Necrosis Factor-alpha; Vascular Resistance; Vomiting

The short term effect of anisodamine, an alkaloid isolated from the chinese herb anisodas tonguticus, on blood flow of uterine and umbilical arteries in 16 pregnant women with pregnancy-induced hypertension (PIH) was investigated by means of pulsed doppler ultrasound technique Results have shown that anisodamine could decrease the A/B ratio, resistant index (RI), and pulsative index (PI) of blood velocity in these arteries with statistical significant difference. Its mechanism of action might be the improving of the rheology in PIH and adjusting the imbalance of TXA2/PGI2. It was suggested that the resistance in uteroplacental circulation was decreased and its perfusion improved, so that favors the fetal growth and development.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Blood Viscosity; Female; Humans; Microcirculation; Placenta; Pre-Eclampsia; Pregnancy; Regional Blood Flow; Solanaceous Alkaloids; Thromboxane B2; Umbilical Arteries; Uterus; Vascular Resistance

The effects of dauricine (Dau), aniso amine (Ani), platelet activating factor (PAF), leukotriene C4 (LTC4) and leukotriene D4 (LTD4) on the production of TXB2 and 6-keto-PGF1 alpha (the stable metabolites of TXA2 and PGI2, respectively) in bovine anterior cerebral arterial smooth muscle cells were studied. The normal quantities of TXB2 and 6-keto-PGF1 alpha produced by bovine anterior cerebral arterial smooth muscle cells were 16 +/- 5 and 464 +/- 24 pg/10(5) cells, respectively, when measured by radioimmunoassay (RIA). The levels of TXB2 and 6-keto-PGF1 alpha in bovine anterior cerebral arterial smooth muscle cells decreased significantly when the cells were treated with Dau or Ani over 20 min. Both drugs inhibited the production of TXB2 and 6-keto-PGF1 alpha in dose (1-100 mumol/L) dependent manner. The bovine anterior cerebral arterial smooth muscle cells were stimulated markedly by LTC4 and LTD4 to produce TXB2 and 6-keto-PGF1 alpha on the same condition even at 0.01 mumol/L. When the cells were treated with PAF over 20 min, TXB2 increased significantly, but 6-keto-PGF1 alpha remained unchanged. If the cells were preincubated with Dau or Ani 20 min before PAF, LTC4 or LTD4 stimulation, the production of TXB2 and 6-keto-PGF1 alpha especially TXB2 were inhibited significantly compared with that of PAF, LTC4 or LTD4 group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Alkaloids; Animals; Benzylisoquinolines; Cattle; Cells, Cultured; Cerebral Arteries; Isoquinolines; Muscle, Smooth, Vascular; Solanaceous Alkaloids; Tetrahydroisoquinolines; Thromboxane B2

The effect of anisodamine on arachidonic acid metabolism in macrophages was studied. The results indicated that the synthesis of PGI2, TXA2 and PGF2 alpha stimulated by phorbol-12-myristate-13-acetate (PMA) and calcium ionophore A23187 was dose and time-dependently inhibited by anisodamine, and preincubation of the cells with anisodamine significantly decreased subsequent PMA and A23187-stimulated synthesis of prostaglandins. An isodamine failed to inhibit exogenous arachidonic acid-stimulated synthesis of prostaglandins. It is suggested that the site of action of anisodamine could be the phospholipase A2 reaction.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcimycin; Macrophages; Mice; Peritoneal Cavity; Solanaceous Alkaloids; Tetradecanoylphorbol Acetate; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Blood Platelets; Cardiopulmonary Bypass; Child; Child, Preschool; Cyclic AMP; Humans; Solanaceous Alkaloids; Thromboxane B2

Topics: Animals; Arachidonic Acids; Fatty Acids, Unsaturated; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Male; Neutrophils; Pleura; Rats; Rats, Inbred Strains; Solanaceous Alkaloids; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cells, Cultured; Dinoprost; Female; Macrophages; Mice; Peritoneal Cavity; Shock, Septic; Solanaceous Alkaloids; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Drugs, Chinese Herbal; Infusions, Intravenous; Male; Rats; Rats, Inbred Strains; Shock, Septic; Solanaceous Alkaloids; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cattle; Dinoprost; Endotoxins; Epithelium; Macrophages; Mice; Solanaceous Alkaloids; Thromboxane B2

Acute disseminated intravascular coagulation (DIC) is a life-threatening condition that may be encountered in many situations, especially in cases of shock with uncontrollable hemorrhage. Anisodamine, an alkaloid extracted from a Chinese herb, is well known for its dramatic therapeutic effect on DIC. Sixty male rabbits were used to establish an acute DIC model. A total of 240 blood samples were taken for laboratory assays of changes in blood coagulation factors, platelet count, platelet adhesion, platelet aggregation, malondialdehyde (MDA), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Changes of the microcirculatory status and the rate of the blood flow in the conjunctival capillaries of 60 rabbits were observed with WXS-II microcirculation microscope. Pathological sections of the lungs and kidneys were studied. Our investigation showed the presence of microthrombi in the microvasculature. After treatment with anisodamine, the prothrombin time stayed in the normal range, fibrinogen consumption was lessened, adenosine-diphosphate-induced platelet aggregation was inhibited, thromboxane B2 and malondialdehyde concentrations were significantly lower than in the control group, and the elevated quantity of 6-keto-PGF1 alpha was spared. We concluded that the anti-platelet-aggregating, microcirculation-facilitating, thromboxane-B2-inhibiting, malondialdehyde-inhibiting, and 6-keto-PGF1 alpha-sparing effects of anisodamine are the important mechanisms of its dramatic therapeutic effect on DIC.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Coagulation; Disseminated Intravascular Coagulation; Kidney; Lung; Male; Malondialdehyde; Microcirculation; Platelet Aggregation; Platelet Count; Rabbits; Regional Blood Flow; Solanaceous Alkaloids; Thromboxane B2

Anisodamine hydrochloride is a vasoactive drug produced in the People's Republic of China that appears efficacious in clinical and experimental bacteremic shock, and about whose mode of action little is known. Suspecting that the drug might work by inhibition of platelet or granulocyte aggregation, or both, we tested it in these systems. Anisodamine proved a modest inhibitor of granulocyte aggregation and a powerful inhibitor of platelet aggregation; thromboxane synthesis was inhibited in anisodamine-treated platelets, further suggesting that the biochemical mode of action might be inhibition of cyclo-oxygenase or thromboxane synthetase.

Topics: Animals; Cell Aggregation; Cricetinae; Depression, Chemical; Granulocytes; Humans; Ibuprofen; Platelet Aggregation; Scopolamine Derivatives; Shock, Septic; Solanaceous Alkaloids; Structure-Activity Relationship; Thromboxane B2; Thromboxanes; Vasodilator Agents