Endothelin receptor antagonist bosentan improves microcirculatory blood flow in splanchnic organs in septic shock

2.50
Hdl Handle:
http://hdl.handle.net/2336/5526
Title:
Endothelin receptor antagonist bosentan improves microcirculatory blood flow in splanchnic organs in septic shock
Authors:
Krejci, Vladimir; Hiltebrand, Luzius B; Erni, Dominique; Sigurdsson, Gisli H
Citation:
Crit. Care Med. 2003, 31(1):203-10
Issue Date:
1-Jan-2003
Abstract:
OBJECTIVE: 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.
Additional Links:
http://gateway.ovid.com/ovidweb.cgi?T=JS&NEWS=N&PAGE=fulltext&AN=00003246-200301000-00031&LSLINK=80&D=ovft

Full metadata record

DC FieldValue Language
dc.contributor.authorKrejci, Vladimir-
dc.contributor.authorHiltebrand, Luzius B-
dc.contributor.authorErni, Dominique-
dc.contributor.authorSigurdsson, Gisli H-
dc.date.accessioned2006-10-23T14:56:47Z-
dc.date.available2006-10-23T14:56:47Z-
dc.date.issued2003-01-01-
dc.identifier.citationCrit. Care Med. 2003, 31(1):203-10en
dc.identifier.issn0090-3493-
dc.identifier.pmid12545016-
dc.identifier.doi10.1097/01.CCM.0000038205.54367.0A-
dc.identifier.otherAAA12-
dc.identifier.urihttp://hdl.handle.net/2336/5526-
dc.description.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.en
dc.language.isoenen
dc.publisherLippincott Williams & Wilkinsen
dc.relation.urlhttp://gateway.ovid.com/ovidweb.cgi?T=JS&NEWS=N&PAGE=fulltext&AN=00003246-200301000-00031&LSLINK=80&D=ovften
dc.subject.meshAcid-Base Equilibriumen
dc.subject.meshAnalysis of Varianceen
dc.subject.meshAnimalsen
dc.subject.meshAntihypertensive Agentsen
dc.subject.meshEndothelinsen
dc.subject.meshGastric Mucosaen
dc.subject.meshHemodynamic Processesen
dc.subject.meshMicrocirculationen
dc.subject.meshShock, Septicen
dc.subject.meshSplanchnic Circulationen
dc.subject.meshStatistics, Nonparametricen
dc.subject.meshSulfonamidesen
dc.titleEndothelin receptor antagonist bosentan improves microcirculatory blood flow in splanchnic organs in septic shocken
dc.typeArticleen
dc.identifier.journalCritical care medicineen
dc.format.digYES-

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