Effects of a specific thromboxane synthetase inhibitor in equine endotoxaemia.
Thromboxane A2 may play a major role in circulatory shock. In some species, thromboxane synthetase inhibitors have a beneficial effect on shock induced by endotoxin, trauma, sepsis and administration of arachidonate. In some shock models, however, results with thromboxane synthetase inhibitors have been conflicting. The effect of UK-38,485, a selective thromboxane inhibitor, was evaluated in ponies injected with endotoxin intraperitoneally. Four groups of ponies were used to compare the effects of endotoxin alone, UK-38,485 alone, treatment with UK-38,485 before endotoxin challenge and treatment with UK-38,485 after endotoxin challenge. Haematological, metabolic, eicosanoid and clinical responses in each group were evaluated. The results indicated that UK-38,485 is an effective inhibitor of thromboxane A2 generation following endotoxin challenge. Prostacyclin values were elevated compared with baseline in ponies administered UK-38,485 and endotoxin. However, prostacyclin values were not significantly different from those of ponies receiving endotoxin alone. Furthermore, UK-38,485 failed to attenuate the haematological, metabolic and clinical manifestations commonly seen in the pony after endotoxin challenge.
Semrad
S D
SD
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602.
Moore
J N
JN
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D005260:Female; D006736:Horses / Q000097:blood*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004731:Endotoxins; D007093:Imidazoles; C039242:dazmegrel; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase