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Updated: Jun 10, 2026
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Lipopolysaccharide Infusion as a Porcine Endotoxemic Shock Model
Published on: December 8, 2023
Endothelin-mediated gut microcirculatory dysfunction during porcine endotoxaemia
A Andersson1, J Fenhammar, E Weitzberg
1Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Sweden. andreas.andersson@karolinska.se
British Journal of Anaesthesia
|August 17, 2010
Summary
Dual endothelin receptor antagonism with tezosentan improved ileal mucosal blood flow in endotoxemia, unlike selective endothelin A-receptor blockade. This suggests endothelin B-receptor involvement in sepsis-induced microcirculatory dysfunction.
Area of Science:
- Sepsis pathophysiology
- Microcirculatory dysfunction
- Pharmacological intervention
Background:
- Endothelin-1 contributes to sepsis-related microcirculatory impairment.
- Investigating endothelin receptor roles in splanchnic blood flow during endotoxemia.
Purpose of the Study:
- To evaluate the efficacy of tezosentan (mixed ET antagonist) and TBC3711 (selective ETA antagonist) in modulating splanchnic blood flow.
- To determine the role of specific endothelin receptors in endotoxemia-induced microcirculatory failure.
Main Methods:
- Endotoxemia induced in anesthetized pigs via intravenous lipopolysaccharide infusion.
- Administration of tezosentan or TBC3711 after 120 minutes.
- Measurement of microcirculatory blood flow (Laser Doppler), superior mesenteric artery flow (SMA(FI)), portal vein flow (PV(FI)), and ileal mucosal Pco₂.
Main Results:
- TBC3711 did not improve splanchnic blood flow or microvascular flow compared to controls.
- Tezosentan increased portal vein flow (PV(FI)) but not SMA(FI).
- Tezosentan significantly improved ileal mucosal microvascular blood flow (MCQ(muc)) and reduced mucosal-arterial Pco₂ gap.
Conclusions:
- Tezosentan demonstrated a direct positive effect on microcirculation without increasing SMA(FI).
- TBC3711 was ineffective in improving regional or microvascular splanchnic blood flow.
- Dual endothelin receptor antagonism is crucial for improving ileal mucosal microcirculation, highlighting the role of the endothelin B-receptor.
