Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure

doi:10.1016/j.ijcard.2010.12.016

International Journal of Cardiology

Volume 157, Issue 1, 17 May 2012, Pages 80-85

https://doi.org/10.1016/j.ijcard.2010.12.016 Get rights and content

Abstract

Background

Small intestinal function may be altered in decompensated chronic heart failure (CHF) and translocating LPS may contribute to systemic inflammation observed in CHF.

Methods

We measured intestinal permeability (melibiose and rhamnose), active (3-O-methyl-d-glucose (3-OMG)) and passive (d-xylose) carrier-mediated absorption in 20 CHF patients (12 edematous and 8 non-edematous) and 8 controls by saccharide absorption technique assessing urinary recovery of orally administered sugars. We additionally measured LPS concentrations in 42 patients with decompensated heart failure and after recompensation.

Results

CHF patients had a 54% reduction of active carrier-mediated intestinal transport compared to controls (p < 0.0001). This reduction was strongest in edematous compared to non-edematous patients and controls (recovery in urine: 13.2 ± 2.0% vs. 20.8 ± 2.4% vs. 36.0 ± 3.7%, all p ≤ 0.05). Patients showed a 34% reduction of passive carrier-mediated transport, strongest in edematous patients (p = 0.006). A greater impairment of active carrier-mediated transport remained significant after adjustment for non-mucosal factors in CHF (p = 0.0004). Non carrier-mediated intestinal permeability was not altered. Data from 42 decompensated patients showed a decrease in LPS after recompensation (p = 0.004).

Edematous patients had highest blood concentrations of LPS, TNF and sTNF-R1 (p < 0.04). CHF patients with abnormal LPS concentrations > 0.50 EU/mL (n = 7) had the highest concentrations of TNF (7.0 ± 1.6 vs. 3.1 ± 0.3 pg/mL, p < 0.02), and sTNF-R1 (3499 ± 52 vs. 1599 ± 219 pg/mL, p = 0.02).

Conclusion

Active carrier-mediated intestinal transport is reduced in decompensated CHF indicating epithelial dysfunction possibly as a consequence of intestinal ischemia. Higher LPS concentrations in edematous CHF relate to inflammation. LPS decreased after recompensation. This suggests a cause/effect relationship between edematous gut wall, epithelial dysfunction and translocating LPS.

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?

Section snippets

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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Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Results

Discussion

Conclusions

Acknowledgements

J Card Fail

J Mol Cell Cardiol

Am J Cardiol

Am J Cardiol

Heart Fail Clin

Gastroenterology

J Am Coll Cardiol

Lancet

Clin Immunol Immunopathol

Gastroenterology

Chest

Ann Thorac Surg

J Vasc Surg

Lancet

J Am Coll Cardiol

Gastroenterology

Surgery

J Hepatol

Lancet

Am J Cardiol

Int J Cardiol