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Thromboxane as a mediator of pulmonary dysfunction during intravascular complement activation in sheep
The American Review of Respiratory Disease
|February 1, 1986
Summary
Thromboxane A2 (TxA2) plays a key role in hypoxemia during complement activation. Inhibiting TxA2 production, but not its action, reduced hypoxemia in sheep, highlighting TxA2
Area of Science:
- Physiology
- Immunology
- Pharmacology
Background:
- Intravascular complement activation triggers thromboxane A2 (TxA2) release.
- This activation leads to pulmonary hypertension, hypoxemia, and increased lung vascular permeability.
Purpose of the Study:
- To investigate the role of TxA2 as a mediator in the physiological responses to intravascular complement activation.
Main Methods:
- Anesthetized sheep received intravenous zymosan-activated plasma (ZAP) infusions.
- Sheep were pretreated with dazoxiben (TxA2 synthetase inhibitor) or SK and F 88046 (TxA2 end-organ antagonist).
- Hemodynamic and gas exchange parameters were monitored and compared between groups.
Main Results:
- Dazoxiben inhibited TxA2 release, while SK and F 88046 did not affect TxA2 levels.
- Neither dazoxiben nor SK and F 88046 altered the hypertensive response to ZAP.
- Dazoxiben significantly attenuated the decrease in partial pressure of arterial oxygen (Pao2), while SK and F 88046 had a lesser effect.
- Lung lymph flow and protein clearance remained unchanged in all groups.
Conclusions:
- TxA2 is a significant mediator of hypoxemia induced by intravascular complement activation.
- Inhibiting TxA2 synthesis is effective in mitigating complement-mediated hypoxemia.
- TxA2 does not appear to mediate the pulmonary hypertensive or increased lung vascular permeability responses to ZAP.