title: Selective intestinal decontamination in advanced chronic heart failure: a pilot trial.
abstract: OBJECTIVE
  Endotoxin, derived from intestinal aerobic Gram-negative bacilli (AGNB), could be an important monocyte activator in chronic heart failure (CHF). The effect of selective decontamination of the digestive tract (SDD) on intracellular monocyte cytokine production, monocyte CD14 expression, circulating endotoxin and cytokines, and flow-mediated dilation (FMD) was studied in patients with severe CHF.
  
  
  RESULTS
  Ten patients with CHF (NYHA class III-IV) were enrolled in a non-placebo controlled pilot trial involving the administration of SDD (polymyxin B, tobramycin) for 8 weeks. One patient was later excluded due to cardiac transplantation. Before treatment, after 4 and 8 weeks therapy, and 6 weeks post-treatment, monocyte CD14 expression, intracellular monocyte production of interleukin-1beta [IL-1beta], interleukin-6 [IL-6], tumour necrosis factor (TNF)-alpha with and without lipopolysaccharide (LPS) stimulation were measured. Concentrations of endotoxin and cytokines (IL-1beta, IL-6, TNF-alpha) were also determined. AGNB in faeces, intestinal endotoxin and FMD were assessed at baseline, after 4 weeks of treatment and 6 weeks post-treatment. SDD eradicated intestinal AGNB (P<0.00001) and decreased faecal endotoxin concentrations (P<0.00001). There was a significant decline in monocyte CD14 expression (P=0.03) and in IL-1beta (P=0.0001), IL-6 (P=0.02) and TNF-alpha (P=0.0002) production after 4 and 8 weeks of treatment in the basal state and for IL-1beta (P=0.008) and IL-6 (P=0.005) after LPS stimulation. FMD significantly improved at 4 weeks and returned to baseline after treatment discontinuation (P=0.002). Circulating concentrations of endotoxin and cytokines remained unchanged.
  
  
  CONCLUSIONS
  Reduction of the intestinal endotoxin pool led to a decrease in monocyte CD14 expression and intracellular cytokine production in patients with severe CHF. The improvement of peripheral endothelial function could be a marker of the anti-inflammatory effect of SDD.
authors.affiliation: Department of Cardiology, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium. Viviane.Conraads@uza.be
authors.forename: Viviane M
authors.initials: VM
authors.lastname: Conraads
authors.forename: Philippe G
authors.initials: PG
authors.lastname: Jorens
authors.forename: Luc S
authors.initials: LS
authors.lastname: De Clerck
authors.forename: Hendrik K
authors.initials: HK
authors.lastname: Van Saene
authors.forename: Margaretha M
authors.initials: MM
authors.lastname: Ieven
authors.forename: Johan M
authors.initials: JM
authors.lastname: Bosmans
authors.forename: Annemie
authors.initials: A
authors.lastname: Schuerwegh
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bridts
authors.forename: Floris
authors.initials: F
authors.lastname: Wuyts
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Stevens
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Mathias
authors.initials: M
authors.lastname: Rauchhaus
authors.forename: Christiaan J
authors.initials: CJ
authors.lastname: Vrints
mesh_terms: D000328:Adult; D000368:Aged; D001431:Bacteriological Techniques; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D003666:Decontamination; D004730:Endothelium, Vascular / Q000378:metabolism / Q000382:microbiology; D004731:Endotoxins / Q000378:metabolism; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D006088:Gram-Negative Aerobic Bacteria / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply / Q000382:microbiology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010865:Pilot Projects; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000502:physiology; D012720:Severity of Illness Index; D014664:Vasodilation / Q000502:physiology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors