Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Sweden.
Br J Anaesth. 2010 Nov;105(5):640-7. doi: 10.1093/bja/aeq217. Epub 2010 Aug 14.
The potent vasoconstrictor endothelin-1 has been implicated in the pathogenesis of the microcirculatory dysfunction seen in sepsis. The mixed endothelin receptor antagonist tezosentan and the selective endothelin A-receptor antagonist TBC3711 were used to investigate the importance of the different endothelin receptors in modulating splanchnic regional blood flow and microvascular blood flow in endotoxaemia.
Eighteen anaesthetized pigs were i.v. infused with endotoxin (Escherichia coli lipopolysaccharide, serotype 0111:b4) for 300 min. After 120 min, six animals received tezosentan and six animals received TBC3711. Six animals served as endotoxin-treated controls. Laser Doppler flowmetry was used to measure microcirculatory blood flow in the liver and ileum. Superior mesenteric artery flow (SMA(FI)) and portal vein flow (PV(FI)) were measured with ultrasonic flow probes, and air tonometry was used to measure Pco₂ in the ileal mucosa.
TBC3711 did not improve splanchnic regional blood flow or splanchnic microvascular blood flow compared with endotoxin-treated controls. Tezosentan increased PV(FI) (P<0.05), but SMA(FI) was not improved compared with the other groups. In the tezosentan group, microvascular blood flow in the ileal mucosa (MCQ(muc)) improved and mucosal-arterial Pco₂ gap decreased (P<0.05 for both) compared with endotoxin-treated controls and the TBC3711 group.
Tezosentan improved MCQ(muc) without any concomitant increase in SMA(FI), implying a direct positive effect on the microcirculation. TBC3711 was not effective in improving regional splanchnic blood flow or splanchnic microvascular blood flow. Dual endothelin receptor antagonism was necessary to improve MCQ(muc), indicating a role for the endothelin B-receptor in mediating the microcirculatory failure in the ileal mucosa.
强效血管收缩素内皮素-1 与脓毒症中所见的微循环功能障碍的发病机制有关。混合内皮素受体拮抗剂替扎森坦和选择性内皮素 A 受体拮抗剂 TBC3711 被用于研究不同的内皮素受体在调节内毒素血症时内脏区域血流和微血管血流中的重要性。
18 只麻醉猪静脉输注内毒素（大肠杆菌脂多糖，血清型 0111:b4）300 分钟。在 120 分钟后，6 只动物接受替扎森坦治疗，6 只动物接受 TBC3711 治疗。6 只动物作为内毒素处理对照。激光多普勒血流仪用于测量肝脏和回肠的微循环血流。肠系膜上动脉血流（SMA(FI)）和门静脉血流（PV(FI)）通过超声血流探头测量，空气张力计用于测量回肠黏膜中的 Pco₂。
与内毒素处理对照组相比，TBC3711 并未改善内脏区域血流或内脏微血管血流。替扎森坦增加了 PV(FI)（P<0.05），但与其他组相比，SMA(FI)并未改善。在替扎森坦组中，与内毒素处理对照组和 TBC3711 组相比，回肠黏膜微血管血流（MCQ(muc)）改善，黏膜-动脉 Pco₂ 间隙减小（均 P<0.05）。
替扎森坦改善了 MCQ(muc)，而没有同时增加 SMA(FI)，暗示对微循环有直接的积极影响。TBC3711 在内脏区域血流或内脏微血管血流方面没有改善作用。双重内皮素受体拮抗作用对于改善 MCQ(muc)是必要的，表明内皮素 B 受体在介导回肠黏膜微循环衰竭中起作用。
