Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in pigs: Effects on intestinal oxygen exchange and energy balance

Karl Träger, Peter Radermacher, Karen Rieger, Robert Grover, Arnim Vlatten, Thomas Iber, Jens Adler, Michael Georgieff, Borislav Šantak

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objectives: To compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L- NMMA), on intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock. Design: Prospective, randomized, experimental study with repeated measures. Setting: Investigational animal laboratory. Subjects: Twenty-seven pigs were divided into three groups: seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA. Interventions: Pigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels. Measurements and Main Results: ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal P(CO2) gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response. Conclusions: Neither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.

Original languageEnglish (US)
Pages (from-to)2007-2014
Number of pages8
JournalCritical Care Medicine
Volume28
Issue number6
StatePublished - 2000
Externally publishedYes

Fingerprint

omega-N-Methylarginine
Septic Shock
Arginine
Norepinephrine
Swine
Oxygen
Arterial Pressure
Pyruvic Acid
Cardiac Output
Energy Metabolism
Lactic Acid
Hydroxyethyl Starch Derivatives
Laboratory Animals
Acidosis
Vasoconstriction
Blood Volume
Endotoxins
Resuscitation
Nitric Oxide Synthase
Lipopolysaccharides

Keywords

  • Endotoxin
  • Gut
  • Lactate
  • N(G)-monomethyl-L-arginine
  • Norepinephrine
  • Pyruvate
  • Regional blood flow
  • Remission spectrophotometry
  • Sepsis
  • Tonometry

ASJC Scopus subject areas

  • Medicine(all)
  • Critical Care and Intensive Care Medicine

Cite this

Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in pigs : Effects on intestinal oxygen exchange and energy balance. / Träger, Karl; Radermacher, Peter; Rieger, Karen; Grover, Robert; Vlatten, Arnim; Iber, Thomas; Adler, Jens; Georgieff, Michael; Šantak, Borislav.

In: Critical Care Medicine, Vol. 28, No. 6, 2000, p. 2007-2014.

Research output: Contribution to journalArticle

Träger, K, Radermacher, P, Rieger, K, Grover, R, Vlatten, A, Iber, T, Adler, J, Georgieff, M & Šantak, B 2000, 'Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in pigs: Effects on intestinal oxygen exchange and energy balance', Critical Care Medicine, vol. 28, no. 6, pp. 2007-2014.
Träger, Karl ; Radermacher, Peter ; Rieger, Karen ; Grover, Robert ; Vlatten, Arnim ; Iber, Thomas ; Adler, Jens ; Georgieff, Michael ; Šantak, Borislav. / Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in pigs : Effects on intestinal oxygen exchange and energy balance. In: Critical Care Medicine. 2000 ; Vol. 28, No. 6. pp. 2007-2014.
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abstract = "Objectives: To compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L- NMMA), on intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock. Design: Prospective, randomized, experimental study with repeated measures. Setting: Investigational animal laboratory. Subjects: Twenty-seven pigs were divided into three groups: seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA. Interventions: Pigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels. Measurements and Main Results: ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal P(CO2) gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response. Conclusions: Neither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.",
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T1 - Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in pigs

T2 - Effects on intestinal oxygen exchange and energy balance

AU - Träger, Karl

AU - Radermacher, Peter

AU - Rieger, Karen

AU - Grover, Robert

AU - Vlatten, Arnim

AU - Iber, Thomas

AU - Adler, Jens

AU - Georgieff, Michael

AU - Šantak, Borislav

PY - 2000

Y1 - 2000

N2 - Objectives: To compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L- NMMA), on intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock. Design: Prospective, randomized, experimental study with repeated measures. Setting: Investigational animal laboratory. Subjects: Twenty-seven pigs were divided into three groups: seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA. Interventions: Pigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels. Measurements and Main Results: ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal P(CO2) gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response. Conclusions: Neither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.

AB - Objectives: To compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L- NMMA), on intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock. Design: Prospective, randomized, experimental study with repeated measures. Setting: Investigational animal laboratory. Subjects: Twenty-seven pigs were divided into three groups: seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA. Interventions: Pigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels. Measurements and Main Results: ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal P(CO2) gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response. Conclusions: Neither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.

KW - Endotoxin

KW - Gut

KW - Lactate

KW - N(G)-monomethyl-L-arginine

KW - Norepinephrine

KW - Pyruvate

KW - Regional blood flow

KW - Remission spectrophotometry

KW - Sepsis

KW - Tonometry

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