Adrenomedullin is increased in the portal circulation during chronic sepsis in rats

Paul J. Matheson, Michael P. Mays, Ryan T. Hurt, Patrick D. Harris, R. Neal Garrison

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: A clinical hallmark of sepsis is an early, hyperdynamic cardiac phase (increased cardiac output) that degrades to a hypodynamic phase, which results in poor gut perfusion and subsequent gastrointestinal (GI) hypoxemia, tissue ischemia, necrosis and loss of gut barrier function. Studies in rat cecal-ligation and puncture suggest that the potent vasodilator adrenomedullin (AM) might initiate or maintain the hypodynamic phase. We hypothesize that AM expression is increased in acute Escherichia coli bacteremia and chronic E coli-Bacteroides fragilis sepsis. Methods: Acute bacteremia: male Sprague-Dawley rats were anesthetized (urethane/α- chloralose), tracheotomized, and cannulated for monitoring blood pressure (MABP) and heart rate (HR) and for infusion of E coli (109 colony-forming units [CFU] E coli per 1 mL normal saline) and blood sampling. Arterial blood was withdrawn for arterial blood gas (ABG) measurements every 60 minutes. After 6 hours, we harvested lung, liver, kidney, spleen, and small intestine tissue samples and drew arterial and portal blood for AM enzyme-linked immunosorbent assay (ELISA). Chronic sepsis: a sterile gauze pad was implanted and animals recovered for 5 days. Twenty-four hours (109 CFU E coli and 10 9 CFU B fragilis per 1 mL normal saline; 1 injection) or 72 hours (2 injections) after the inoculation of the back sponge, rats were anesthetized, intubated, and cannulated as above. MABP, HR, and ABG were measured for 1 hour before tissue and serum harvest for AM ELISA. Results: Sepsis increased HR and MABP in all groups. Acute sepsis caused a respiratory alkalosis and pH was also elevated in chronic sepsis. Serum AM levels were increased in all groups compared with baseline and remained elevated at every time point, but were not different between saline controls and septic animals at any time point, except for the portal serum from the 72-hourr chronic sepsis, which was elevated. Conclusions: These data suggest that surgical manipulation alone is sufficient to stimulate AM secretion, most probably from endothelial cells. While the AM levels were decreasing at 72 hours compared with 6 hours or 24 hours in the arterial blood and the saline control portal blood, it remained elevated in the septic portal samples, suggesting that the sepsis-induced increase of AM was derived from the gut by a different mechanism than that which elevated arterial serum levels.

Original languageEnglish (US)
Pages (from-to)519-525
Number of pages7
JournalAmerican journal of surgery
Volume186
Issue number5
DOIs
StatePublished - Nov 2003

Keywords

  • Adrenomedullin
  • Escherichia coli, Bacteroides fragilis
  • Microcirculation
  • Multiple organ dysfunction
  • Multiple organ system failure
  • Sepsis
  • Shock
  • Small intestine

ASJC Scopus subject areas

  • Surgery

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