Krejci Vladimir, Hiltebrand Luzius B, Erni Dominique, Sigurdsson Gisli H
Department of Anesthesiology, Inselspital, University Hospital of Berne, Switzerland.
Crit Care Med. 2003 Jan;31(1):203-10. doi: 10.1097/00003246-200301000-00031.
Splanchnic ischemia is believed to play an important role in the development of multiple organ dysfunction in septic shock. The vasoconstrictor peptide endothelin can produce an intense and sustained splanchnic vasoconstriction and is increased in sepsis. The aim of this investigation was to study the effects of an endothelin antagonist on microcirculatory blood flow in multiple abdominal organs during septic shock.
Prospective, controlled animal study.
University-affiliated research laboratory.
Fifteen anesthetized and mechanically ventilated pigs.
Septic shock was induced by fecal peritonitis. After 120 mins of sepsis, eight animals received 10 mg/kg bosentan intravenously followed by an intravenous infusion at 5 mg x kg-1 x hr-1 whereas seven (controls) received isotonic saline. At 240 mins after induction of sepsis both groups received hydroxyethyl starch, 20 mL/kg intravenously, to convert hypodynamic septic shock to hyperdynamic sepsis.
Microcirculatory blood flow was measured simultaneously and continuously in the jejunal muscularis, pancreas, liver, kidney, skeletal muscle, and gastric, jejunal, and colon mucosa by using a multiple-channel laser Doppler flow meter. After 120 mins, all animals had developed signs of hypodynamic sepsis with decreased cardiac index, mean arterial blood pressure, and gastric mucosal pH. Microcirculatory blood flow in the pancreas and liver had decreased by 20% and in the jejunal muscularis by >40% (p <.01) whereas it remained virtually unchanged in the gastric, jejunal, and colonic mucosa. After 240 mins, cardiac index, mean arterial blood pressure, gastric mucosal pH, and microcirculatory blood flow in the gastric mucosa, colon mucosa, jejunal muscularis, and pancreas had all deteriorated in the controls, whereas in the bosentan-treated group, cardiac index and microcirculatory blood flow in the pancreas, gastric, and colon mucosa improved. During hyperdynamic sepsis, cardiac index increased above baseline in both groups but significantly more in the bosentan group. In the control group, microcirculatory flow returned to baseline in most tissues except in skeletal muscle and jejunal muscularis. In the bosentan group, microcirculatory flow returned to or increased above baseline in all tissues except in the muscularis of the jejunum.
The endothelin receptor antagonist bosentan significantly improved microcirculatory blood flow in many splanchnic organs and in peripheral tissues during septic shock. The results of this study are consistent with the hypothesis that endothelin plays an important role in the regulation of microcirculatory blood flow in splanchnic as well as in peripheral tissues during septic shock.
内脏缺血被认为在脓毒性休克所致多器官功能障碍的发展过程中起重要作用。血管收缩肽内皮素可引起强烈且持续的内脏血管收缩，且在脓毒症时水平升高。本研究旨在探讨内皮素拮抗剂对脓毒性休克期间多个腹部器官微循环血流的影响。
前瞻性对照动物研究。
大学附属研究实验室。
15只麻醉并机械通气的猪。
通过粪性腹膜炎诱导脓毒性休克。脓毒症120分钟后，8只动物静脉注射10mg/kg波生坦，随后以5mg·kg⁻¹·hr⁻¹的速度静脉输注；7只（对照组）动物输注等渗盐水。脓毒症诱导240分钟后，两组均静脉注射20mL/kg羟乙基淀粉，将低动力型脓毒性休克转变为高动力型脓毒症。
使用多通道激光多普勒血流仪同时连续测量空肠肌层、胰腺、肝脏、肾脏、骨骼肌以及胃、空肠和结肠黏膜的微循环血流。120分钟后，所有动物均出现低动力型脓毒症体征，心脏指数、平均动脉血压和胃黏膜pH值降低。胰腺和肝脏的微循环血流减少了20%，空肠肌层减少超过40%（p<0.01），而胃、空肠和结肠黏膜的微循环血流基本未变。240分钟后，对照组的心脏指数、平均动脉血压、胃黏膜pH值以及胃黏膜、结肠黏膜、空肠肌层和胰腺的微循环血流均恶化，而在波生坦治疗组，心脏指数以及胰腺、胃和结肠黏膜的微循环血流得到改善。在高动力型脓毒症期间，两组的心脏指数均高于基线水平，但波生坦组升高更为显著。在对照组中，除骨骼肌和空肠肌层外，大多数组织的微循环血流恢复至基线水平。在波生坦组中，除空肠肌层外，所有组织的微循环血流恢复至基线水平或高于基线水平。
内皮素受体拮抗剂波生坦在脓毒性休克期间显著改善了许多内脏器官和外周组织的微循环血流。本研究结果与以下假设一致，即内皮素在脓毒性休克期间内脏及外周组织的微循环血流调节中起重要作用。
