title: Thromboxane as a mediator of pulmonary dysfunction during intravascular complement activation in sheep.
abstract: Intravascular complement activation results in thromboxane (TxA2) production, pulmonary hypertension, hypoxemia, and increased lung vascular permeability. The purpose of this study was to determine the role of TxA2 as a mediator of these responses. Experiments were made in anesthetized sheep subjected to intravenous injections of zymosan-activated plasma (ZAP) every 30 min for 4 h. Sheep were pretreated with dazoxiben, a TxA2 synthetase inhibitor, or SK and F 88046, a TxA2 end-organ antagonist, and the results were compared with those from untreated sheep. Dazoxiben, but not SK and F 88046, inhibited TxA2 release. The hypertensive response averaged 74 +/- 3 cm H2O after each injection of ZAP in untreated sheep. Neither drug altered this response. Pao2 decreased an average of 20 +/- 1 mmHg in untreated sheep, 3 +/- 1 mmHg in dazoxiben-treated sheep, and 11 +/- 1 mmHg in SK and F 88046-treated sheep. Increases in lung lymph flow and lymph protein clearance were unaffected by treatment. TxA2 appears to be an important mediator of hypoxemia during intravascular complement activation.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D003167:Complement Activation; D006976:Hypertension, Pulmonary / Q000139:chemically induced; D000860:Hypoxia / Q000139:chemically induced; D007093:Imidazoles / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects; D008171:Lung Diseases / Q000209:etiology*; D010949:Plasma; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep / Q000097:blood; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D007093:Imidazoles; C034339:SK&F 88046; D013449:Sulfonamides; C029166:dazoxiben; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D015054:Zymosan