Thrombocytopaenia, Thromboxane And Prostacyclin Production During The Forssman Reaction In The Guinea-Pig: Effect Of A Thromboxane Synthetase Inhibitor

1981 ◽  
Author(s):  
J Westwick ◽  
K Butler ◽  
A Honey ◽  
S Krishnamurthi ◽  
V V Kakkar

Intra venous (iv) injection of Forssman antibody into the guinea-pig (GP) is known to result in a rapid antigen antibody reaction in the lungs leading to bronchospasm and thrombocytopaenia. Death as a result of Forssman shock has been shown to be complement and platelet dependentGroups of 5 Duncan-Hartley GP (350-400g) received either 0.2ml (sub lethal groups) or 0.6ml (lethal groups) of rabbit anti Forssman antiserum (RAFA) iv, then 5ml blood samples were collected via carotid artery cannula, into 0.5ml ice cold EDTA (lOOmM) and indomethacin (180μM) mixture at 0, 1, 3 and 5 min. post injection. The blood samples were rapidly centrifuged at 15,000g for 3 min, plasma removed and frozen at -20°C until assayed. The plasma was then assayed for TxB2 and 6-oxo-PGF1α using specific RIA’s. There was a marked TxB2 production during the thrombocytopaenia with a concomitant small increase in 6-oxo-PGF1α production.However, when groups of 5 GPs were dosed iv with 0, 1, 3 or 10 mg/kg of UK-37, 248, a potent and selective thromboxane synthetase inhibitor, 3 mins prior to 0.2ml of RAFA the resulting thrombocytopaenia was not inhibited at 0, 0.5, 1, 2, 5, 10 and 15 min post RAFA. Thus thromboxane production does not appear to be contributory to the Forssman induced thrombocytopaenia in the GP.

1983 ◽  
Vol 50 (03) ◽  
pp. 703-706 ◽  
Author(s):  
Jon Dale ◽  
Erik Thaulow ◽  
Erik Myhre ◽  
John Parry

SummaryTwenty-four men received either placebo, 0.1 g of the thromboxane synthetase inhibitor dazoxiben, 0.25 or 1.0 g of acetylsalicylic acid (ASA). Dazoxiben reduced the maximal rate of collagen-induced platelet aggregation, but less than did ASA. ASA abolished secondary, ADP-induced aggregation, dazoxiben not. Both drugs prolonged the bleeding-time.Plasma thromboxane B2 (TxB2) levels did not change significantly after dazoxiben, whereas the prostacyclin metabolite 6-keto-PGF1α rose. The larger dose of ASA reduced both TxB2 and 6-keto-PGF1α in plasma. Whole blood was allowed to clot in order to estimate prostaglandin metabolism. Both drugs prevented thromboxane production effectively. Formation of 6-keto-PGF1α decreased by 95 per cent after ASA but was more than doubled after dazoxiben.Dazoxiben is a selective and effective thromboxane synthetase inhibitor, but has a weaker effect on platelet reactivity than ASA, possibly because endoperoxide formation is not prevented.


1986 ◽  
Vol 43 (4) ◽  
pp. 455-468 ◽  
Author(s):  
Hiroshi Mikashima ◽  
Hiroshi Ochi ◽  
Yoshito Muramoto ◽  
Hiroshi Yasuda ◽  
Mineo Tsuruta ◽  
...  

Lipids ◽  
1987 ◽  
Vol 22 (3) ◽  
pp. 159-162 ◽  
Author(s):  
J. J. F. Belch ◽  
A. R. Saniabadi ◽  
K. McLaughlin ◽  
C. D. Forbes

1982 ◽  
Vol 57 (1) ◽  
pp. 74-82 ◽  
Author(s):  
Tomio Sasaki ◽  
Susumu Wakai ◽  
Takao Asano ◽  
Kintomo Takakura ◽  
Keiji Sano

✓ The efficacy of thromboxane synthetase inhibitor in the prevention of cerebral vasospasm after subarachnoid hemorrhage (SAH) was evaluated in a prolonged experiment using dogs. Changes in the diameter of the basilar artery were followed by angiography, and morphological changes were studied by photomicroscopy and electron microscopy. As a thromboxane synthetase inhibitor, OKY-1581 (sodium-(E)-3-(4(-3-pyridylmethyl)phenyl)-2-methylacrylate)was used. Dogs received intravenous injections of 160 mg of OKY-1581 dissolved in 2 ml of physiological saline immediately after subarachnoid blood injection. Subsequently, the animals received continuous intravenous infusion of the drug at the rate of 4 gm/50 ml/24 hours until sacrifice 4 days after induction of SAH. Control dogs received subarachnoid blood injection without treatment with OKY-1581. Angiographic examination revealed that the late spasm was almost completely abolished by the treatment with OKY-1581. Early spasm was also prevented, but the drug's effect was less prominent than it was on the late spasm. Morphological study revealed degenerative changes in the endothelium and myonecrotic changes in the tunica media following SAH in the basilar arteries of the treated as well as the untreated dogs. However, corrugation of the internal elastic lamina was almost completely absent in the treated dogs. The above results indicate that a disproportionate synthesis of thromboxane A2 plays an important role in the evolution of chronic cerebral vasospasm following SAH, and that drugs such as OKY-1581 that selectively inhibit thromboxane synthetase might be useful in the prevention of vasospasm.


Life Sciences ◽  
1984 ◽  
Vol 35 (2) ◽  
pp. 221-228 ◽  
Author(s):  
Edwin K. Jackson ◽  
Howard D. Uderman ◽  
William A. Herzer ◽  
Robert A. Branch

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