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BW755C modifies endotoxin-induced respiratory failure in pigs
American Journal of Veterinary Research
|March 1, 1987
Summary
BW755C, a dual inhibitor of cyclooxygenase and lipoxygenase pathways, partially blocked endotoxemia's pulmonary effects in pigs. Lipoxygenase metabolites may influence vascular permeability and cardiac index.
Area of Science:
- Pharmacology
- Pulmonary Medicine
- Inflammation Research
Background:
- Endotoxemia triggers significant pulmonary responses, including hypertension and impaired gas exchange.
- Arachidonic acid metabolism via cyclooxygenase (COX) and lipoxygenase (LOX) pathways plays a role in these responses.
- BW755C is a dual inhibitor of both COX and LOX pathways.
Purpose of the Study:
- To evaluate the effects of BW755C on the porcine pulmonary response to endotoxemia.
- To determine the specific roles of COX and LOX metabolites in endotoxin-induced pulmonary dysfunction.
Main Methods:
- Anesthetized pigs received Escherichia coli endotoxin intravenously.
- BW755C was administered before and during endotoxemia.
- Pulmonary hemodynamics, gas exchange, lung water, and bronchoalveolar lavage were assessed.
Main Results:
- BW755C blocked or modified endotoxin-induced pulmonary hypertension, increased vascular resistance, and altered oxygen gradients.
- BW755C also affected lung water, albumin concentration, cardiac index, lung compliance, and platelet counts.
- The blockade magnitude by BW755C was similar to indomethacin (COX inhibitor), suggesting limited LOX role in vasoconstriction and gas exchange impairment.
Conclusions:
- BW755C effectively modified acute pulmonary responses to endotoxemia in pigs.
- While COX metabolites appear dominant in pulmonary vasoconstriction and gas exchange issues, LOX metabolites may contribute to altered vascular permeability, cardiac index, and platelet counts.