Selective intestinal decontamination in advanced chronic heart failure: a pilot trial.
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.
Conraads
Viviane M
VM
Department of Cardiology, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium. Viviane.Conraads@uza.be
Jorens
Philippe G
PG
De Clerck
Luc S
LS
Van Saene
Hendrik K
HK
Ieven
Margaretha M
MM
Bosmans
Johan M
JM
Schuerwegh
Annemie
A
Bridts
Chris H
CH
Wuyts
Floris
F
Stevens
Wim J
WJ
Anker
Stefan D
SD
Rauchhaus
Mathias
M
Vrints
Christiaan J
CJ
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
D015415:Biomarkers; D016207:Cytokines; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors