Thromboxane as a mediator of pulmonary dysfunction during intravascular complement activation in sheep.
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.
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
D007093:Imidazoles; C034339:SK&F 88046; D013449:Sulfonamides; C029166:dazoxiben; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D015054:Zymosan