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Bedeutung des Darmtraktes für die Entstehung von systemischer Inflammation und Kachexie bei chronischer Herzinsuffizienz : Pathophysiological role of the gastrointestinal system for the development of systemic Inflammation and cachexia in patients with chronic heart failure

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  • Title:
    Bedeutung des Darmtraktes für die Entstehung von systemischer Inflammation und Kachexie bei chronischer Herzinsuffizienz : Pathophysiological role of the gastrointestinal system for the development of systemic Inflammation and cachexia in patients with chronic heart failure
  • Author: Sandek, Anja
  • Contributor: Prof. Dr. Med. Christiane E. Angermann
  • Subjects: 610 Medizin Und Gesundheit ; 610 Medical Sciences; Medicine ; Ddc:610 ; Heart Failure ; Cachexia ; Gut ; Bacteria ; Inflammation
  • Publication Details: Berlin: Freie Universität Berlin Universitätsbibliothek
  • Language: German
  • Description: Chronic heart failure is associated with low-grade systemic inflammation and anabolic-catabolic imbalance, that may lead to prognostically relevant cardiac cachexia in advanced stages of the disease. Aim of this work was to characterize the role of the gastrointestinal tract for the development of systemic inflammation and cachexia in patients with chronic heart failure.We found that patients with chronic heart failure have a reduced intestinal blood flow and an edema of the intestinal wall. These alterations are accompanied by a decreased specific intestinal absorption function, permit bacterial overgrowth in the mucus layer adjacent to the apical surface of the colonic mucosa. Furthermore, our studies show that the concentration of adherent juxtamucosal gut bacteria correlates with blood lipopolysaccharide(LPS)-antibodies indicating a systemic response to bacteria in heart failure. Thus, interaction between gut bacteria and immune system of the host, local Inflammation and an increase in intestinal permeability of the intestinal mucosa are conceivable. The fact that higher blood concentrations of LPS were associated with higher degree of inflammation in edematously decompensated patients and that these inflammatory markers decreased after recompensation suggests a cause/effect relationship between edematous gut wall, epithelial dysfunction and translocating LPS.This points to a vicious circle where increased permeability due to lower blood supply leads to an augmented interaction with gut bacteria and local Inflammation again weakening intestinal barrier. As an indicator of systemic relevance of these alterations, we found a correlation of a greater bowel wall thickness of the sigmoid with higher blood C-reactive Protein (CrP) as a hallmark of systemic Inflammation. Furthermore, a greater bowel wall thickness of the ascending colon suggestive of a bowel wall edema, correlated with a higher concentration of blood leucocytes in these patients with heart failure. Low intestinal blood flow in celiac trunk and upper mesenteric artery, correlated with higher blood CrP, too. These results are consistent with a contribution of intestinal hemodynamics to prognostically relevant systemic inflammation. An implementation of the immunological status of the patients should improve risk stratification in heart failure. We were able to show a risk stratification model including 4 factors (soluble tumor necrosis factor-receptor 1 (sTNF-R 1), uric acid, left ventricular ejection fraction and NYHA class) to be highly prognostic in our cohort and therefore integrated intestinal alterations through markers of systemic Inflammation such as sTNF-R 1. In multivariate Regression analysis with limited statistical power, low intestinal arterial blood flow, right ventricular dysfunction, congestive liver dysfunction and low serum albumin were predictive of the presence of cachexia. Research is needed to determine whether interventions that specially increase mesenteric blood flow inhibit the growth of juxtamucosal bacteria, reduce inflammation and GI symptoms, and ameliorate cardiac cachexia in patients with advanced HF. Our studies of intestinal barrier dysfunction in heart failure pave the way for interventional studies that target gut bacteria as source of systemic Inflammation and cardiovascular pathogenesis.
  • Creation Date: 2014

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