Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure
Introduction
Chronic heart failure (CHF) is recognised as a clinical syndrome affecting many organ systems. Several concepts have been proposed to explain the underlying pathophysiology [1], [2], [3]. Whilst considerable evidence supports a central role for immune activation in the pathophysiology of CHF [4], the origin of inflammatory cytokine production remains poorly understood. It has been suggested that CHF patients display enhanced translocation of endotoxin (lipopolysaccharide, LPS) across the intestinal wall, derived from gut bacteria [5]. LPS is a potent stimulus for immune activation. The subsequent increase of circulating cytokines is thought to contribute to both the central and peripheral manifestations of CHF [6].
The gut has received only little systematic research in patients with CHF so far [7]. The intestine serves as an important immunological barrier both in structural terms and since it contains approximately 75% of the body's immune tissue [8]. Changes of intestinal cell integrity in humans can be assessed non-invasively after oral administration of monosaccharides and disaccharides using different combinations and exactly defined amounts [9]. These sugars are absorbed from the small intestine via different trans- and paracellular pathways. Both active and passive channels are involved. Determination of urinary recovery of these sugars can be used to obtain a functional assessment of specific pathways that contribute to small intestinal permeability.
Recently, we have shown morphological and functional alterations with thickened bowel wall throughout the entire large bowel, and profound changes in passive carrier mediated transport and intestinal permeability in stable, compensated CHF patients [10].
The objective of the present study was to investigate intestinal absorption function in non-edematous and edematous CHF patients. Not only passive-carrier mediated but also active-carrier mediated transport was studied.
We sought to determine three questions: First, are there functional changes of the intestine in edematously decompensated patients? Second, is active carrier-mediated transport altered in addition to reduced passive carrier-mediated transport as seen in compensated CHF patients? Third, do patients during edematous decompensation display higher concentrations of LPS?
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Study population
In the first CHF group we studied twenty patients (19 male, age 69 ± 2 years) and 8 healthy control subjects (6 male, age 68 ± 3 years). The diagnosis of CHF was based on a history of typical symptoms of at least 6 months, cardiomegaly, and documented left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤ 40%) [11]. The aetiology of CHF (LVEF 29 ± 5%) was ischemic in 15 (75%) and idiopathic in the remaining 5 patients (25%). No participant had evidence of acute infection, rheumatoid
Results
The clinical characteristics and biochemical parameters of the first study population are given in Table 1. CHF patients had increased serum endothelin-1 levels compared to healthy controls (3.08 ± 0.18 vs. 2.09 ± 0.36 pg/mL, p < 0.011). This increase was strongest in edematous compared to non-edematous patients and controls (3.15 ± 0.2 vs. 2.99 ± 0.29 vs. 2.09 ± 0.36 pg/mL, ANOVA-p < 0.04).
Discussion
This study shows for the first time that active carrier-mediated trans-cellular intestinal absorption of 3-OMG across the small intestinal wall is impaired in edematous CHF patients compared to non-edematous patients and healthy controls. Edematous patients displayed the highest plasma concentrations of LPS among these groups of subjects. Plasma concentrations of TNF, sTNF-R1, sTNF-R2 and in trend sCD14 were highest in edematous patients and increased progressively from healthy subjects to
Conclusions
Our study assessed for the first time differential intestinal absorptive function in edematous and non-edematous patients with CHF and aggravated renal function. The data suggest that intestinal “endothelial” (epithelial) dysfunction, either as a result of bowel wall ischemia and/or bowel wall congestion, is present in CHF patients with a functional amelioration of the intestinal wall. Whether bacterial translocation across the intestine occurs in CHF patients is still a matter of debate as the
Acknowledgements
We thank Christa Liebenthal for analysing cytokine concentrations. We also acknowledge the assistance and great support of Dr. Ian S Menzies, FRCPath Path MBBS. We are very grateful to our study participants. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [42].
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