Inhibition of thromboxane biosynthesis in splanchnic ischemia shock.
Administration of dazoxiben (5 mg/kg, i.v.), which effectively suppressed plasma thromboxane concentrations, decreased the number of dogs that deteriorated into shock following a temporary (3-hr) splanchnic artery occlusion (SAO). Dazoxiben pretreatment also moderated the rise of plasma prostacyclin, but it augmented circulating prostaglandin E2 following the release of SAO. These alterations in arachidonic acid metabolism were accompanied by a moderation in the rise of plasma beta-glucuronidase activity, suggesting a moderation of tissue damage in the ischemic splanchnic region, and mitigation of the progressive hemodynamic deterioration caused by the SAO. The possible existence of causal relationships between the plasma eicosanoid concentrations, extent of damage in the ischemic splanchnic region, hemodynamic deterioration, and ultimate production of circulatory failure in dogs subjected to SAO are discussed.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D005260:Female; D005966:Glucuronidase / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007511:Ischemia / Q000150:complications / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D012769:Shock / Q000209:etiology / Q000503:physiopathology*; D013152:Splanchnic Circulation; D013929:Thromboxane B2 / Q000097:blood*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014655:Vascular Resistance / Q000187:drug effects
D007093:Imidazoles; C029166:dazoxiben; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D005966:Glucuronidase; D013930:Thromboxane-A Synthase; D007213:Indomethacin