Adverse effects of hydroxyethyl starch (HES 130/0.4) on intestinal barrier integrity and metabolic function are abrogated by supplementation with Albumin

Abstract

BackgroundVolume resuscitation with hydroxyethyl starch (HES) is controversially discussed and we recently showed that HES perfusion impairs endothelial and epithelial intestinal barrier integrity. Here we investigated whether Albumin containing HES solutions are superior to HES alone in maintaining intestinal barrier function.MethodsAn isolated perfused model of the mouse small intestine was used to investigate the effects of: (i) 3 % Albumin (Alb), (ii) 3 % HES or (iii) 1.5 % HES/1.5 % Albumin (HES/Alb). Intestinal morphology, cell damage, metabolic functions, fluid shifts and endothelial/epithelial barrier permeability were evaluated. Potentially involved signaling mechanisms (Erk1/2, Akt and Stat5 phosphorylation) were screened.ResultsHES induced histomorphological damage (p < 0.01 vs. Alb), by trend elevated the amount of luminal intestinal fatty acid binding protein and reduced galactose uptake (p < 0.001 vs. Alb). Luminal and lymphatic flow rates were increased (p < 0.001 vs. Alb), while vascular flow was decreased (p < 0.001 vs. Alb) during HES perfusion. HES also increased the vascular to luminal FITC-dextran transfer (p < 0.001 vs. Alb), pointing towards a fluid shift from the vascular to the luminal and lymphatic compartments during HES perfusion. Addition of Alb (HES/Alb) reversed all adverse effects of HES (p < 0.05 vs. HES), restored barrier integrity (p < 0.05 vs. HES) and improved metabolic function of the intestine (p < 0.001 vs. HES; p < 0.05 vs. Alb). Mechanistically, HES/Alb perfusion resulted in an increased phosphorylation of Erk1/2 and Akt kinases (p < 0.001 vs. HES), while Stat5 remained unchanged.ConclusionsAlbumin supplementation abrogates the adverse effects of HES in the intestine and underlying mechanism may function via phosphorylation of Erk1/2 and Akt. Albumin containing HES solutions are superior to HES alone and may improve the suitability of HES in the clinic.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0810-3) contains supplementary material, which is available to authorized users.

Modulation of Intestinal Epithelial Glycocalyx Development by Human Milk Oligosaccharides and Non‐Digestible Carbohydrates

“…Also increased albumin adsorption may contribute to the anti‐pathogenic effects of the glycocalyx as it has been shown that a supplement of albumin results in less adhesion of, for example, Staphylococcus epidermidis , Staphylococcus aureus, Pseudomonas aeruginosa . An increased albumin adsorption also contributes to enhanced barrier function as it protects during volume resuscitation in hydroxyethyl starch solutions against adverse effects of hydroxyethyl starch on intestinal cells, metabolic functions, fluid shifts, and epithelial barrier permeability . This suggests that the enhancing effects on albumin adsorption of hMOs and NDCs may not only strengthen the glycocalyx structure but also protect against pathogen adhesion and maintain under luminal changes the gut epithelial barrier.…”

Effects of different ischemic preconditioning strategies on physiological and cellular mechanisms of intestinal ischemia/reperfusion injury: Implication from an isolated perfused rat small intestine model

“…The detailed surgical procedure and ex-vivo perfusion was described by our group earlier [13,14]. Briefly, rats were anesthetized by inhalation Sevoflurane and additional intraperitoneal injection of Ketamine.…”

“…For online analysis of fluid homeostasis all emanating liquids are quantified by use of three balances (9 to 11). Constant flow perfusion is applied by a syringe pump (12) and roller pump (13). The vascular perfusate is prewarmed, oxygenated, and pH equilibrated with tempered hollow fiber dialyzer flushed with carbogen gas (14).…”

“…Details about the respective methods have been published recently [13,17]. Briefly, to determine the intestinal uptake of galactose, the luminal perfusion buffer was supplemented with 30 mM of lactose.…”

Has goal directed fluid therapy and glycocalyx a role in enhanced recovery after anesthesia?

“…[16] There are many animal and human studies on the effects of different fluid items on the GCX with conflicting results. [1718192021] Crystalloids and colloids do have different distribution patterns: crystalloids mostly remain in the extracellular space, therefore, they are commonly used for ongoing extracellular losses. If beyond that in case of acute surgical bleeding, isotonic preparations such as hydroxyethyl starch to be considered.…”