EPOPROSTENOL IMPROVES MUCOSAL TISSUE OXYGEN TENSION IN AN ACUTE ENDOTOXEMIC PIG MODEL

The objective of the present study was to determine the effects of increasing dosages of continuously infused epoprostenol (PGI), a prostacyclin analog, on intestinal oxygen supply and jejunal mucosal tissue oxygen tension in an acute endotoxic pig model. Jejunal mucosal tissue PO2, oxygen saturation of jejunal microvascular hemoglobin, and gut microvascular blood flow were investigated. Systemic hemodynamic variables, mesenteric-venous and systemic acid base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after Escherichia coli LPS administration, and at 20-min intervals during incremental PGI infusion (n = 8; 25, 50, 100, and 200&mgr;g·kg−1·h−1, respectively); or infusion of an equal amount of isotonic sodium chloride solution (n = 7). LPS infusion led to a significant decrease in mucosal tissue oxygen tension and microvascular hemoglobin oxygen saturation. Epoprostenol infusion led to a significant, dose-dependent increase in cardiac index and systemic oxygen delivery. Mucosal tissue oxygen tension and microvascular hemoglobin oxygen saturation increased after PGI administration and even returned to more-than-baseline values. Continuously infused PGI increased intestinal hemoglobin oxygen saturation and mucosal tissue oxygen tension in a dose-dependent manner mainly due to an increase in villus blood flow in this acute endotoxic pig model.

[1]  W. Buurman,et al.  EVIDENCE FOR INTESTINAL AND LIVER EPITHELIAL CELL INJURY IN THE EARLY PHASE OF SEPSIS , 2007, Shock.

[2]  H. Knotzer,et al.  Microcirculatory function monitoring at the bedside—a view from the intensive care , 2007, Physiological measurement.

[3]  K. Vollebregt,et al.  The NO donor SIN‐1 improves intestinal–arterial Pco2 gap in experimental endotoxemia: an animal study , 2007, Acta anaesthesiologica Scandinavica.

[4]  V. Wenzel,et al.  Arginine vasopressin reduces intestinal oxygen supply and mucosal tissue oxygen tension. , 2005, American journal of physiology. Heart and circulatory physiology.

[5]  Licheng Wu,et al.  Influence of the critically ill state on host-pathogen interactions within the intestine: Gut-derived sepsis redefined , 2003, Critical care medicine.

[6]  C. Ince,et al.  Opening the microcirculation: can vasodilators be useful in sepsis? , 2002, Intensive Care Medicine.

[7]  R. Hotchkiss,et al.  Endothelial cell apoptosis in sepsis , 2002, Critical care medicine.

[8]  C. Ng,et al.  Role of Prostacyclin on Microcirculation in Endotoxin-Induced Gastroprotection in Rats: A Microdialysis Study , 2002, Shock.

[9]  D. Mercer,et al.  Lipopolysaccharide-Induced Gastrointestinal Injury in Rats: Role of Surface Hydrophobicity and Bile Salts , 2002, Shock.

[10]  C. Ng,et al.  Prostacyclin analogue (OP-2507) induces delayed ex vivo neutrophil apoptosis and attenuates reperfusion-induced hepatic microcirculatory derangement in rats. , 2001, Shock.

[11]  P. Grände,et al.  Beneficial effects of low-dose prostacyclin on cat intestinal perfusion during endotoxemia as evaluated with microdialysis and oxygen transport variables , 2001, Critical care medicine.

[12]  F. Moore,et al.  POST‐INJURY MULTIPLE ORGAN FAILURE: THE ROLE OF THE GUT , 2001, Shock.

[13]  M. Fink,et al.  Cytosolic ionized Ca2+modulates chemical hypoxia-induced hyperpermeability in intestinal epithelial monolayers. , 1998, American journal of physiology. Gastrointestinal and liver physiology.

[14]  J. Oropello,et al.  Effects of the stable prostacyclin analogue iloprost on mesenteric blood flow in porcine endotoxic shock. , 1997, Critical care medicine.

[15]  P. Grände,et al.  Low-dose prostacyclin has potent capillary permeability-reducing effect in cat skeletal muscle in vivo. , 1997, The American journal of physiology.

[16]  P. Radermacher,et al.  Prostacyclin (PGI2): new aspects of an old substance in the treatment of critically ill patients , 1997, Intensive Care Medicine.

[17]  E. Martin,et al.  Effect of endotoxemia on intestinal villus microcirculation in rats. , 1996, The Journal of surgical research.

[18]  H. Becker,et al.  The effects of prostacyclin on gastric intramucosal pH in patients with septic shock , 1995, Intensive Care Medicine.

[19]  A. Macpherson,et al.  Intestinal permeability: an overview. , 1995, Gastroenterology.

[20]  J. Vane,et al.  Pharmacodynamic profile of prostacyclin. , 1995, The American journal of cardiology.

[21]  D. Crutchley,et al.  Effects of prostacyclin analogs on the synthesis of tissue factor, tumor necrosis factor-alpha and interleukin-1 beta in human monocytic THP-1 cells. , 1994, The Journal of pharmacology and experimental therapeutics.

[22]  H. Sparr,et al.  Vasomotion induces regular major oscillations in jejunal mucosal tissue oxygenation. , 1994, The American journal of physiology.

[23]  C. Arroyo,et al.  The scavenging of hydroxyl radical(.OH) by a prostacyclin analogue, taprostene. , 1994, Chemico-biological interactions.

[24]  J. Horton,et al.  Pentoxifylline protects splanchnic prostacyclin synthesis during mesenteric ischemia/reperfusion. , 1994, Prostaglandins.

[25]  M. Fink.  Gastrointestinal mucosal injury in experimental models of shock, trauma, and sepsis , 1991, Critical care medicine.

[26]  U. Haglund,et al.  The role of prostanoids in the feline intestinal vascular and central haemodynamic responses to i.v. infusion of live E. coli. , 1987, Acta physiologica Scandinavica.

[27]  J. Hurley,et al.  The effect of prostacyclin on the adhesion of leucocytes to injured vascular endothelium , 1984, The Journal of pathology.

[28]  K. Sirinek,et al.  Prostacyclin-mediated gastric cytoprotection is dependent on mucosal blood flow. , 1982, Surgery.

[29]  D. Granger,et al.  Vasoactive agents and splanchnic oxygen uptake. , 1982, The American journal of physiology.

[30]  H. Bohlen.  Intestinal tissue PO2 and microvascular responses during glucose exposure. , 1980, The American journal of physiology.

[31]  J. Vane,et al.  An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation , 1976, Nature.

[32]  T. Rimmele,et al.  Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock. , 2008, British journal of anaesthesia.

[33]  R. Gryglewski,et al.  Prostacyclin among prostanoids. , 2008, Pharmacological reports : PR.

[34]  S. Pulletz,et al.  Sympathetic modulation of intestinal microvascular blood flow oscillations in experimental endotoxemia. , 2003, Clinical hemorheology and microcirculation.

[35]  R. Hotchkiss,et al.  Molecular biology of multiple organ dysfunction syndrome: injury, adaptation, and apoptosis. , 2000, Surgical infections.

[36]  K. Sirinek,et al.  Prostacyclin selectively enhances blood flow in areas of the GI tract prone to stress ulceration. , 1984, Journal of Trauma.