Hydroxyethyl Starch (HES 130/0.4) Impairs Intestinal Barrier Integrity and Metabolic Function: Findings from a Mouse Model of the Isolated Perfused Small Intestine

Abstract

BackgroundThe application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine.MethodsAn isolated perfused model of the mouse small intestine was established and intestines were vascularly perfused with a modified Krebs-Henseleit buffer containing 3% Albumin (N=7) or 3% HES (130/0.4; N=7). Intestinal metabolic function (galactose uptake, lactate-to-pyruvate ratio), edema formation (wet-to-dry weight ratio), morphology (histological and electron microscopical analysis), fluid shifts within the vascular, lymphatic and luminal compartments, as well as endothelial and epithelial barrier permeability (FITC-dextran translocation) were evaluated in both groups.ResultsCompared to the Albumin group, HES perfusion did not significantly change the wet-to-dry weight ratio and lactate-to-pyruvate ratio. However, perfusing the small intestine with 3% HES resulted in a significant loss of vascular fluid (p<0.01), an increased fluid accumulation in the intestinal lumen (p<0.001), an enhanced translocation of FITC-dextran from the vascular to the luminal compartment (p<0.001) and a significantly impaired intestinal galactose uptake (p<0.001). Morphologically, these findings were associated with an aggregation of intracellular vacuoles within the intestinal epithelial cells and enlarged intercellular spaces.ConclusionA vascular perfusion with 3% HES impairs the endothelial and epithelial barrier integrity as well as metabolic function of the small intestine.

Hydroxyethyl starches in equine medicine

“…Furthermore, HES have recently been found to impair the intestinal barrier integrity and metabolic function of the murine small intestine in an in vitro study. 119 The relevance of these findings for the use of HES in equine gastrointestinal patients is currently unknown. The large majority of equine patients receiving HES for resuscitation or COP support having gastrointestinal disorders adds to the reservations and debate about the use of HES.…”

“…There is some evidence that hypertonic saline has better volume expansion effects than HES in horses and dogs and might, therefore, be a more rational choice for volume resuscitation. Furthermore, HES have recently been found to impair the intestinal barrier integrity and metabolic function of the murine small intestine in an in vitro study . The relevance of these findings for the use of HES in equine gastrointestinal patients is currently unknown.…”

“…Furthermore, HES show better restoration of splanchnic microcirculation than isotonic saline . However, HES has also been demonstrated to have negative effects on intestinal barrier and function . It is currently unclear how these findings translate to horses undergoing exploratory laparotomy.…”

La influencia de la administración de solución de lactato de Ringer o HES 130 / 0,4 en la integridad de la mucosa del intestino delgado en un modelo porcino de hemorragia controlada = The influence of administering Ringer's Lactate solution or HES 130/0.4 on the integrity of the small intestinal mucosa in a pig model of controlled haemorrhage

“…The intestine has an extremely import role in the metabolism, inflammation and sepsis, however information about the effects of HES solutions on the intestinal mucosa and overall function and barrier integrity is very limited. A small number of studies on the effects of HES in the intestine have been performed in different species (Feng et al 2007;Lobo et al 2008;Kimberger et al 2009;Lu et al 2015;Wong et al 2015).…”

“…The results of a more recent study using an isolated perfused model of the mouse small intestine suggested that the vascular perfusion with clinically relevant concentrations of HES significantly impairs the endothelial and epithelial barrier integrity and the metabolic function of the intestine, when compared with albumin (Wong et al 2015). In this study, mice that had their small intestine perfused with 3% HES 130/0.4 solution showed a significant loss of vascular fluid, an increased fluid accumulation in the intestinal lumen, an enhanced translocation of fluorescein isothiocyanate-dextran from the vascular to the luminal compartment and a significantly impaired intestinal galactose uptake.…”