title: Thromboxane and prostacyclin in acute lung injury caused by venous air emboli in unanesthetized sheep.
abstract: In 4 unanesthetized sheep with lung lymph fistulas we studied the role of thromboxane A2 (TxA2) in the lung microvascular injury caused by 4 h of venous air embolism. In each sheep, we did paired air embolism experiments: control and after giving the TxA2-synthetase inhibitor, U63,557A. Inhibition of TxA2-synthetase did not affect the hemodynamic response to air emboli; lung lymph flow increased slowly but to the same final rate as with air alone. The pulmonary production of TxA2, estimated as the lymph concentration of thromboxane B2 (TxB2) X lymph flow, increased during air embolism in the control experiment but increased much less when TxA2-synthetase was inhibited. Similarly, prostacyclin (PGI2) production increased during air embolism but was reduced when TxA2-synthetase was inhibited. Our results suggest that TxA2 does not mediate the pulmonary hypertension caused by venous air emboli, but it might modulate the increase in lymph flow by acting on the lymphatic pump or affecting hemodynamics in the pulmonary microcirculation. Our results do not support that TxA2 mediates the injury caused by venous air embolism. Pulmonary production of PGI2 seems to depend on the pulmonary production of TxA2, as shown by the parallel changes of their metabolites during air embolization.
authors.forename: M R
authors.initials: MR
authors.lastname: Bonsignore
authors.forename: T R
authors.initials: TR
authors.lastname: Rice
authors.forename: P M
authors.initials: PM
authors.lastname: Dodek
authors.forename: N C
authors.initials: NC
authors.lastname: Staub
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004618:Embolism, Air / Q000097:blood*; D011464:Epoprostenol / Q000097:blood*; D008168:Lung / Q000098:blood supply*; D008208:Lymphatic System / Q000187:drug effects / Q000502:physiology; D008833:Microcirculation / Q000187:drug effects; D011651:Pulmonary Artery / Q000503:physiopathology; D012756:Sheep; D013928:Thromboxane A2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000097:blood*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D013931:Thromboxanes; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase