Administration of a receptor antagonist for platelet-activating factor during equine endotoxaemia.
Platelet-activating factor (PAF) is an important mediator of endotoxaemia and various PAF receptor antagonists prevent many of the adverse effects of experimental endotoxaemia in laboratory animals. In this study a specific PAF receptor antagonist was used to investigate the role of PAF in equine endotoxaemia. At an interval of not greater than 10 days, 6 horses were each challenged with endotoxin and endotoxin with concurrent administration of SRI 63-441, a PAF receptor antagonist. The order of the treatments was randomised. Clinical signs, serum biochemical and coagulation profiles, and platelet aggregation in vitro were monitored in all horses for 24 h after treatment. Challenge with endotoxin increased maximal platelet aggregation induced by PAF. This response was blocked by administration of SRI 63-441 concurrently with endotoxin. No changes in percentage maximal platelet aggregation to ADP or collagen were noted after administration of endotoxin. The PAF receptor antagonist delayed the onset of fever, tachycardia, leucopenia and lactic acidaemia. Lack of more profound beneficial alterations of the horses' responses to endotoxin may have been due to the low dose of endotoxin administered in this model or to only partial effectiveness of SRI 63-441 in blocking the effects of endotoxin-induced PAF.
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602.
J B
JB
Carrick
D D
DD
Morris
J N
JN
Moore
D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004731:Endotoxins / Q000097:blood*; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit / Q000662:veterinary; D006734:Horse Diseases / Q000139:chemically induced / Q000188:drug therapy*; D006736:Horses; D007958:Leukocyte Count / Q000187:drug effects / Q000662:veterinary; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins; D011806:Quinolinium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D043562:Receptors, G-Protein-Coupled; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004731:Endotoxins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011806:Quinolinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; C050531:SRI 63-441; D013929:Thromboxane B2; D000990:Antithrombin III