Effect of increased cardiac output on liver blood flow, oxygen exchange and metabolic rate during longterm endotoxin-induced shock in pigs

Borislav Šantak, Peter Radermacher, Jens Adler, Thomas Iber, Karen Rieger, Ulrich Wachter, Josef Vogt, Michael Georgieff, Karl Träger

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

1. We investigated hepatic blood flow, O2 exchange and metabolism in porcine endotoxic shock (Control, n = 8; Endotoxin, n = 10) with administration of hydroxyethylstarch to maintain arterial pressure (MAP) > 60 mmHg. 2. Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O2 saturation (Hb-O2%) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glyercol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of [6,6-2H2]-glucose. 3. Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O2 delivery and uptake nor mean intracapillary Hb-O2% and Hb-O2% frequency distributions. 4. Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative (P < 0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios. 5. During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro- and microcirculatory O2 supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well-preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O2 requirements of gluconeogenesis.

Original languageEnglish (US)
Pages (from-to)1689-1697
Number of pages9
JournalBritish Journal of Pharmacology
Volume124
Issue number8
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Endotoxins
Cardiac Output
Shock
Swine
Oxygen
Liver
Lactic Acid
Glucose
Pyruvic Acid
Hemoglobins
Septic Shock
Alanine
Arterial Pressure
Gluconeogenesis
Colloids
Isotopes
Glycerol
Oxidation-Reduction

Keywords

  • Capillary haemoglobin O saturation
  • Endotoxin
  • Gluconeogenesis
  • Heparic glucose precursor uptake
  • Hepatic blood flow
  • Hepatic O exchange
  • Lactate/pyruvate ratio
  • Remission spectrophotometry
  • Septic shock
  • Stable isotope infusion

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of increased cardiac output on liver blood flow, oxygen exchange and metabolic rate during longterm endotoxin-induced shock in pigs. / Šantak, Borislav; Radermacher, Peter; Adler, Jens; Iber, Thomas; Rieger, Karen; Wachter, Ulrich; Vogt, Josef; Georgieff, Michael; Träger, Karl.

In: British Journal of Pharmacology, Vol. 124, No. 8, 1998, p. 1689-1697.

Research output: Contribution to journalArticle

Šantak, Borislav ; Radermacher, Peter ; Adler, Jens ; Iber, Thomas ; Rieger, Karen ; Wachter, Ulrich ; Vogt, Josef ; Georgieff, Michael ; Träger, Karl. / Effect of increased cardiac output on liver blood flow, oxygen exchange and metabolic rate during longterm endotoxin-induced shock in pigs. In: British Journal of Pharmacology. 1998 ; Vol. 124, No. 8. pp. 1689-1697.
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AU - Šantak, Borislav

AU - Radermacher, Peter

AU - Adler, Jens

AU - Iber, Thomas

AU - Rieger, Karen

AU - Wachter, Ulrich

AU - Vogt, Josef

AU - Georgieff, Michael

AU - Träger, Karl

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N2 - 1. We investigated hepatic blood flow, O2 exchange and metabolism in porcine endotoxic shock (Control, n = 8; Endotoxin, n = 10) with administration of hydroxyethylstarch to maintain arterial pressure (MAP) > 60 mmHg. 2. Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O2 saturation (Hb-O2%) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glyercol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of [6,6-2H2]-glucose. 3. Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O2 delivery and uptake nor mean intracapillary Hb-O2% and Hb-O2% frequency distributions. 4. Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative (P < 0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios. 5. During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro- and microcirculatory O2 supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well-preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O2 requirements of gluconeogenesis.

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KW - Hepatic blood flow

KW - Hepatic O exchange

KW - Lactate/pyruvate ratio

KW - Remission spectrophotometry

KW - Septic shock

KW - Stable isotope infusion

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