title: Sustained infection induces 2 distinct microvascular mechanisms in the splanchnic circulation.
abstract: BACKGROUND
  Altered intestinal blood flow during systemic inflammation leads to organ dysfunction. Mucosal ischemia occurs during sepsis despite an increase in portal blood flow. We hypothesized that separate mechanisms are active in the large resistance and small mucosal microvessels to account for this dichotomy.
  
  
  METHODS
  Chronic infection was induced in rats by bacterial inoculation (Escherichia coli and Bacteroides fragilis) of an implanted subcutaneous sponge. Separate groups were studied at 24 and 72 hours after a single inoculation of bacterium or 24 hours after a second inoculation (ie, 72 hours of sepsis). Time-matched controls were used for each group. Intravital microscopy of the terminal ileum was used to assess endothelial-dependent vasodilation to acetylcholine (10(-9) to 10(-5) mol/L) in resistance (A(1)) and premucosal (A(3)) arterioles. Threshold sensitivity (-log of 20% response dose) was calculated from dose response curves for each animal.
  
  
  RESULTS
  Vasodilator sensitivity to acetylcholine in A(1) arterioles was significantly decreased at 24 hours, and these changes persisted up to 72 hours after a single bacterial inoculation. There was no change in the dilator sensitivity of A(3) arterioles after a single inoculation. When there was a challenge with a second bacterial inoculation, there was a reversal of the A(1) dilator response and an increase in A(3) sensitivity.
  
  
  CONCLUSIONS
  An initial septic event results in a decrease in dilator reactivity in the resistance A1 arterioles that persists for at least 72 hours. A sustained septic challenge results in increased dilator reactivity in both A(1) and A(3) vessels. This enhanced sensitivity during sepsis suggests that more than 1 therapeutic approach to preservation of intestinal blood flow will be necessary.
authors.affiliation: Department of Surgery, Department of Physiology and Biophysics, and Center for Excellence in Applied Microcirculatory Research, University of Louisville and Veterans Affair Medical Center, Louisville, KY, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: D A
authors.initials: DA
authors.lastname: Spain
authors.forename: P J
authors.initials: PJ
authors.lastname: Matheson
authors.forename: C
authors.initials: C
authors.lastname: Vaughn
authors.forename: P D
authors.initials: PD
authors.lastname: Harris
authors.forename: R N
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001442:Bacteroides Infections / Q000378:metabolism / Q000503:physiopathology*; D001441:Bacteroides fragilis; D004927:Escherichia coli Infections / Q000378:metabolism / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000098:blood supply / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D018715:Microscopy, Video; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine