Effect of hydroxyethyl starch on vascular leak syndrome and neutrophil accumulation during hypoxia

Dieterich, Hans-Jürgen; Weissmüller, Thomas; Rosenberger, Peter; Eltzschig, Holger K.

doi:10.1097/01.ccm.0000218814.77568.bc

Cited by 57 publications

(35 citation statements)

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“…To identify which adenosine receptor is responsible for regulating vascular permeability, we used a previously characterized in vitro model of endothelial barrier function. 9,18,34 Here, we performed siRNA-mediated stable repression of individual ARs and studied endothelial barrier function in normoxic or posthypoxic endothelia (HMEC-1 cells, 48 hours at 2% oxygen concentration). As shown for the A2BAR, transcript and protein levels were less than 20% of control-transfected cells and the induction of A2BR expression that normally occurs as a result of hypoxia 9,33 was largely abolished ( Figure 1A,B).…”

Section: A2bar Attenuates Hypoxia-associated Endothelial Leakage In Vmentioning

confidence: 99%

A2B adenosine receptor dampens hypoxia-induced vascular leak

Eckle¹,

Faigle²,

Grenz

et al. 2008

Blood

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271

329

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IntroductionPrevious studies have implicated extracellular nucleotide metabolites, predominantly adenosine, as triggers of endogenous protective mechanisms in a number of acute injury models. [1][2][3][4][5][6][7] Extracellular adenosine is derived primarily through phosphohydrolysis of adenosine 5Ј-monophosphate (AMP). Ecto-5Ј-nucleotidase (CD73), a ubiquitously expressed ectoenzyme, is the pacemaker of this reaction. 8 Studies on the role of CD73 in tissue-injury showed that cd73 Ϫ/Ϫ mice develop profound vascular leakage and pulmonary edema upon hypoxia exposure. 8 Once generated into the extracellular space, adenosine can signal through any of 4 G-protein coupled adenosine-receptors (ARs: A1AR/A2AAR/A2BAR/A3AR). All of these receptors are expressed on vascular endothelia 9 and have been implicated in tissue-protection in different models of injury. [1][2][3]7,[10][11][12][13][14][15][16][17][18] Changes in vascular barrier function closely coincide with tissue injury of many etiologies, and result in fluid loss, edema, and organ dysfunction. [19][20][21] The predominant barrier (ϳ90%) to movement of macromolecules across a blood vessel wall is presented by the vascular endothelium. 20,22 Under physiologic conditions, macromolecules such as albumin (molecular weight ϳ70 kD) can cross the endothelial monolayer via a paracellular route (eg, by passing between adjacent endothelia) with some contribution of transcellular passage. 23,24 Endothelial barrier function correlates inversely with the size of molecules that can gain entry into tissues and differs between tissues of different origins. Endothelial permeability is highly regulated and may increase markedly upon exposure to inflammatory stimuli (eg, lipopolysaccharide, bacteria, bacterial compounds, prostaglandins, reactive oxygen species, leukotrienes) or adverse conditions such as ischemia or hypoxia. 18,20,[25][26][27][28][29] Given that activation of ARs can lead to an elevation of intracellular cAMP, and that elevated cAMP in endothelia promotes barrier function, 20,30 we considered the possibility of endothelial AR-signaling to regulate vascular permeability. In contrast to previous studies that found tissue protection during hypoxia or inflammation through signaling pathways involving the A2AAR, 1,3,7,31,32 the present studies conclude that the A2BAR is central to the control of vascular leak in hypoxia. Methods Cell cultureHuman microvascular endothelial cells (HMEC)-1 were cultured as described previously. 9,18 For preparation of experimental HMEC-1 monolayers, confluent endothelial cells were seeded at approximately less than 10 5 cells/cm 2 onto either permeable polycarbonate inserts or 100-mm Petri dishes. Endothelial cell purity was assessed by phase microscopic "cobblestone" appearance and uptake of fluorescent acetylated low-density lipoprotein. Stable repression of AR expression by siRNAWith the help of the siRNA Wizard (www.sirnawizard.com; InvivoGen, San Diego, CA) the following primer sequences were chosen within the coding region of the g...

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Section: A2bar Attenuates Hypoxia-associated Endothelial Leakage In Vmentioning

confidence: 99%

A2B adenosine receptor dampens hypoxia-induced vascular leak

Eckle¹,

Faigle²,

Grenz

et al. 2008

Blood

Self Cite

271

329

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“…HES solutions have been shown to attenuate the acute inflammatory response [18][19][20][21] , mitigate endothelial barrier dysfunction and vascular leak [18,22] , and preserve intestinal barrier function [17] . Small clinical trials have suggested superiority of HES solutions for resuscitation of the microcirculation in sepsis [22] .…”

Section: Type Of Fluid Therapymentioning

confidence: 99%

Controversies in fluid therapy: Type, dose and toxicity

McDermid

Raghunathan

Romanovsky

et al. 2014

WJCCM

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Fluid therapy is perhaps the most common intervention received by acutely ill hospitalized patients; however, a number of critical questions on the efficacy and safety of the type and dose remain. In this review, recent insights derived from randomized trials in terms of fluid type, dose and toxicity are discussed. We contend that the prescription of fluid therapy is context-specific and that any fluid can be harmful if administered inappropriately. When contrasting ''crystalloid vs colloid'', differences in efficacy are modest but differences in safety are significant. Differences in chloride load and strong ion difference across solutions appear to be clinically important. Phases of fluid therapy in acutely ill patients are recognized, including acute resuscitation, maintaining homeostasis, and recovery phases. Quantitative toxicity (fluid overload) is associated with adverse outcomes and can be mitigated when fluid therapy based on functional hemodynamic parameters that predict volume responsiveness and minimization of non-essential fluid. Qualitative toxicity (fluid type), in particular for iatrogenic acute kidney injury and metabolic acidosis, remain a concern for synthetic colloids and isotonic saline, respectively. Physiologically balanced crystalloids may be the ''default'' fluid for acutely ill patients and the role for colloids, in particular hydroxyethyl starch, is increasingly unclear. We contend the prescription of fluid therapy is analogous to the prescription of any drug used in critically ill patients.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Fluid therapy; Resuscitation; Critical illness; Peri-operative; Toxicity; Saline; Crystalloid; Colloid Core tip: Fluid therapy is exceedingly common in acutely ill patients; however, numerous questions on the efficacy and safety of fluid therapy in terms of the type and dose remain. Fluid therapy prescription is contextspecific and any fluid type can be harmful if administered inappropriately. When considering crystalloids versus colloids, differences in efficacy are modest but the risk of kidney toxicity and bleeding complications with hydroxyethyl starch appear more significant. The differences in chloride load across crystalloid solutions appears to have physiologic and clinically important effects, in particular for contributing to hyperchloremic metabolic acidosis, kidney injury and greater utilization of renal replacement therapy associated with 0.9% saline. Fluid therapy should be viewed as analogous to the prescription of any drug in acutely ill patients.McDermid RC, Raghunathan K, Romanovsky A, Shaw AD, Bagshaw SM. Controversies in fluid therapy: Type, dose and toxicity.

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“…[14][15][16][17][18][24][25][26][27][28][29] We shared the commonly held perception that both volume effect and molecule characteristics are among the most important factors in organ protection; however, the current study demonstrated that the HES molecule plays a role in hepatoprotection against reperfusion injury. The infused volume of HES solution (13 mLÁkg -1 ) adjusted to the weight of the rats was within the doses reported for volume repletion in clinical studies.…”

Section: Discussionmentioning

confidence: 74%

“…[7][8][9][10][11][12][13] Best known for their use as intravascular volume expanders, HES solutions are also associated with microcirculatory improvement and antiinflammatory properties. [14][15][16][17][18] Despite their adverse effects in other settings, namely, on renal function, coagulation, and tissue storage, it was suggested previously that the older high molecular weight HES can reduce the deleterious effect of IRI. 14,19 Distinct types of HES show clear differences in pharmacokinetic, clinical efficacy, and adverse effects.…”

Section: Résumémentioning

confidence: 99%

L’hydroxyéthylamidon 130/0,4 atténue les dommages hépatiques précoces causés par les lésions d’ischémie/reperfusion

Catré

Viana

Cabrita

et al. 2010

Can J Anesth/J Can Anesth

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Purpose Ischemia/reperfusion injury (IRI) remains a clinical challenge. We tested the hypothesis that fluid therapy using hydroxyethyl starch (HES) 130/0.4 during the early phase of IRI in rat liver decreases markers of hepatic injury. Methods We induced liver IRI in three groups of rats anesthetized with ketamine and chlorpromazine by means of 60 min of segmental hepatic ischemia followed by 120 min of reperfusion. At the onset of reperfusion, Group 1 (IRI ? HES; n = 12) was given 13 mLÁkg -1 of HES; Group 2 (IRI ? HS; n = 12) received the same volume of 7.5% saline (HS), and Group 3 (IRI-only; n = 12) received no fluid. Three other groups of 12 animals each were shamoperated and received the same fluid as the test groups. We euthanized the animals after three hours, drew blood for alanine aminotransferase (ALT) quantification, and took ischemic liver samples for histomorphological study.Results Serum ALT activity was greater in all of the IRI groups than in the sham-operated animals. The ALT activity was 1,081 ± 575 IUÁL -1 in IRI ? HES Group 1; 2,363 ± 1,839 IUÁL -1 in IRI ? HS Group 2; and 2,866 ± 2,491 IUÁL -1 in IRI-only Group 3. There was a statistically significant difference between the IRI ? HES and the IRIonly groups (P = 0.001), but not between the IRI ? HS and the IRI-only groups (P [ 0.05). Likewise, histological scores were greater in all IRI groups compared with the sham-operated animals. Scores were higher in the IRI-only group (median 3.5) than in the groups receiving fluid (IRI ? HES median 2; IRI ? HS median 3). The difference between IRI ? HES and IRI-only was statistically significant (P = 0.008) but not so between IRI ? HS and IRI-only (P [ 0.05). Conclusions Giving HES 130/0.4 attenuates rat liver IRI compared with no fluid, while giving HS does not. This suggests a role for HES in hepatoprotection associated with liver IRI. RésuméObjectif La le´sion d'ische´mie/reperfusion (IR) reste un de´fi clinique. Nous avons e´mis l'hypothe`se qu'une the´rapie liquidienne a`base d'hydroxye´thylamidon (HES) 130/0,4 administre´e pendant la phase pre´coce d'IR dans un mode`le he´patique de rat, diminuerait les marqueurs de la le´sion he´patique. Méthode Nous avons provoque´une le´sion d'IR au niveau du foie dans trois groupes de rats anesthe´sie´s à la ke´tamine et a`la chlorpromazine en cre´ant une ische´mie he´patique segmentaire de 60 min suivie de 120 min de reperfusion. Au de´but de la reperfusion, le groupe 1 (IR ? HES; n = 12) a reçu 13 mLÁkg -1 de HES; le groupe 2 (IR ? HS; n = 12) a reçu le meˆme volume de se´rum physiologique 7,5 % (HS), et le groupe 3 (IR seule;This investigation was supported, in part, by research funds of the School of Medicine of the University of Coimbra (GAPI 08/08).

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Effect of hydroxyethyl starch on vascular leak syndrome and neutrophil accumulation during hypoxia

Abstract: Taken together, these results indicate that hypoxia-induced increases in vascular leakage and acute inflammation are attenuated by hydroxyethyl starch treatment.

Cited by 57 publications

References 45 publications

A2B adenosine receptor dampens hypoxia-induced vascular leak

A2B adenosine receptor dampens hypoxia-induced vascular leak

Controversies in fluid therapy: Type, dose and toxicity

L’hydroxyéthylamidon 130/0,4 atténue les dommages hépatiques précoces causés par les lésions d’ischémie/reperfusion

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