Endothelin receptor antagonist bosentan improves microcirculatory blood flow in splanchnic organs in septic shock
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
CitationCrit. Care Med. 2003, 31(1):203-10
AbstractOBJECTIVE: 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. DESIGN: Prospective, controlled animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Fifteen anesthetized and mechanically ventilated pigs. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.
- Dynamic study of the distribution of microcirculatory blood flow in multiple splanchnic organs in septic shock.
- Authors: Hiltebrand LB, Krejci V, Banic A, Erni D, Wheatley AM, Sigurdsson GH
- Issue date: 2000 Sep
- Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis.
- Authors: Krejci V, Hiltebrand LB, Sigurdsson GH
- Issue date: 2006 May
- Redistribution of microcirculatory blood flow within the intestinal wall during sepsis and general anesthesia.
- Authors: Hiltebrand LB, Krejci V, tenHoevel ME, Banic A, Sigurdsson GH
- Issue date: 2003 Mar
- Effects of vasopressin on microcirculatory blood flow in the gastrointestinal tract in anesthetized pigs in septic shock.
- Authors: Hiltebrand LB, Krejci V, Jakob SM, Takala J, Sigurdsson GH
- Issue date: 2007 Jun
- Mixed endothelin receptor antagonism with tezosentan improves intestinal microcirculation in endotoxemic shock.
- Authors: Andersson A, Fenhammar J, Frithiof R, Weitzberg E, Sollevi A, Hjelmqvist H
- Issue date: 2008 Sep