Interactions between platelet activating factor and eicosanoids during endotoxic shock in anaesthetized pigs

Area of Science:

• Cardiovascular Physiology
• Immunology
• Pharmacology

Background:

• Endotoxemia, induced by lipopolysaccharide (LPS), triggers a complex inflammatory response.
• Platelet-activating factor (PAF) and eicosanoids are implicated as mediators in endotoxic shock.
• The precise role of PAF and eicosanoids in mortality versus survival during endotoxic shock requires further elucidation.

Purpose of the Study:

• To investigate the effects of platelet activating factor (PAF) on eicosanoid release during endotoxic shock.
• To determine the role of PAF and eicosanoids in early mortality and circulatory collapse in a porcine model.
• To assess the therapeutic potential of a PAF receptor antagonist (BN 52021) in mitigating endotoxic shock.

Main Methods:

• Anesthetized pigs were infused with Escherichia coli endotoxin (LPS) via the superior mesenteric artery.
• Plasma levels of various mediators, including eicosanoids, were measured.
• Animals were either untreated, treated with the PAF receptor antagonist BN 52021, or administered exogenous PAF.

Main Results:

• No significant alterations in eicosanoid levels were observed in non-survivors of LPS infusion.
• Survivors exhibited a transient increase in eicosanoid concentrations.
• BN 52021 treatment prevented circulatory collapse in survivors and reduced cyclooxygenase products, but did not affect survival rates or LTB(4) release.

Conclusions:

• Prostanoid formation appears secondary to PAF release in LPS-induced circulatory collapse in survivors.
• PAF-prostanoid interactions are important in the pathophysiology of endotoxic shock survival.
• PAF and eicosanoids seem to have a negligible role in early mortality during endotoxic shock, suggesting other mediators are involved.