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Işın Güneş,1 Nuran Süngü,2 Aydan Kılıçarslan,2 Volkan Şıvgın,3 Metin Alkan,3 Ayşegül Küçük,4 Hakan Boyunağa,5 Yusuf Ünal,3 Mustafa Arslan3 1Department of Anaesthesiology and Reanimation, Erciyes University Medical Faculty, Kayseri, Turkey; 2Department of Pathology, Yıldırım Beyazıt University Medical Faculty, Ankara, Turkey; 3Department of Anaesthesiology and Reanimation, Gazi University Medical Faculty, Ankara, Turkey; 4Department of Physiology, Dumlupinar University Medical Faculty, Kütahya, Turkey; 5Department of Biochemistry, Kirikkale University Medical Faculty, Kirikkale, Turkey Objective: This study was conducted since the effects of colloid solutions on the renal system remain controversial and need to be adequately studied in animals. We aimed to evaluate the effects of hydroxyethyl starch (Voluven) on the kidney tissue of rats with late renal failure due to ureteral obstruction. Materials and methods: Rats were divided into four groups: Group C, control; Group HES, hydroxyethyl starch solution (HES) 130/0.4 (Voluven®); Group UUO, unilateral ureteral obstruction (UUO); and Group UUO-HES, UUO-HES 130/0.4 (Voluven®). In the groups with ureteral obstruction, the distal part of the right ureter was accessed and sutured through a lower abdominal incision under ketamine anesthesia. Any signs of late-stage renal failure were evaluated after three weeks. Rats in the HES group and the renal failure-HES group were administered with HES 130/0.4 as a single intravenous dose of 20 mL/kg. After a follow-up of 24 hours, intra-abdominal blood sample was collected, and the rats were sacrificed. Biochemical and histopathological parameters were then evaluated. Results: Ureteral obstruction significantly increased urea and creatinine levels. In addition, when the UUO-HES and HES groups were compared, the administration of HES increased urea and creatinine levels in the UUO-HES group. Nitric oxide enzyme activity and malondialdehyde levels have significantly increased in the UUO groups. In addition, HES significantly increased nitric oxide activity and malondialdehyde levels in the UUO-HES group, in comparison with the HES group. The activity of caspases 3 and 8 was significantly increased in the UUO groups. In addition, HES significantly increased the activity of caspases 3 and 8 in the UUO-HES group, in comparison with the HES group. Light microscopy revealed significant changes in the UUO groups, especially in the obstructed kidneys. Conclusion: If indicated, HES should be used with caution in cases of UUO, but not in the cases of bilateral ureteral obstruction. Other aspects of these findings, including the clinical significance and practical applications, merit further experimental and clinical investigation. Keywords: unilateral ureteral obstruction, hydroxyethyl starch solution 130/0.4, caspase 3, caspase 8, malondialdehyde, nitric oxide

Aim: The administration of plasma expanders is crucial for managing critically ill patients across a range of clinical conditions, including major surgery, hemorrhagic shock, and trauma. However, the effects of hydroxyethyl starch (HES) on erythrocyte aggregation remain controversial. For this reason, we aimed to investigate the effects of HES 130/0.4, performed renal insufficiency by experimentally unilateral ureteral obstruction, on erythrocyte deformability. Materials and Methods: A total of 24 rats were divided into 4 groups; Control, HES 130/0.4, Ureter Obstruction (UO) and UO-HES130/0.4. Urethral obstruction groups were treated with ketamine anesthesia with a low abdominal incision and reached to the distal of right ureter and sutured with 2.0 mersilen then waited for 3 weeks for late term renal insufficiency. 20 mL.kg-1 of HES 130/0.4 (Voluven) were infused intravenously to the HES 130/0.4 and UO-HES130/0.4 group. After 24-hour, rats were sacrificed. Deformability measurements were performed using 5% haematocrit in a phosphate-buffered saline (PBS) buffer. Results and Discussion: Relative resistance was increased in all groups compared to the control group (p<0.0001). In all groups, erythrocyte deformability index was found to be significantly higher than the control group (Group C-Group HES, p=0.023, Group C- Group UO, p<0.0001, Group C-Group UO-HES, p<0.0001). UO-HES group had significantly increased erythrocyte deformability index compared with the HES group (p=0.031, p=0.021, respectively). It was determined that HES 130/0.4 application did not change erythrocyte deformability in ureteral obstructed rats (p=0.785). Conclusion: The use of HES 130/0.4 has no negative effects on erythrocyte deformability in ureteral obstructed rats. We think that indications should be used correctly when using HES 130/0.4. [ABSTRACT FROM AUTHOR]

Background During systemic inflammation, leucocytes are activated and extravasate into damaged tissue. Activation and recruitment are influenced by different mechanisms, including the interaction of leucocytes with platelets and neutrophil extracellular traps (NET) formation. Here, we investigated the molecular mechanism by which hydroxyethyl starch (HES 130/0.4) dampens systemic inflammation in vivo. Methods Systemic inflammation was induced in C57Bl/6 wild-type mice by caecal ligation and puncture and cytokine concentrations in the blood, neutrophil recruitment, platelet–neutrophil aggregates, and NET formation were investigated in vivo. Intravascular adherent and transmigrated neutrophils were analysed by intravital microscopy (IVM) of the cremaster muscle and the kidneys. Flow chamber assays were used to investigate the different steps of the leucocyte recruitment cascade. Results By using flow cytometry, we demonstrated that HES 130/0.4 reduces neutrophil recruitment into the lung, liver, and kidneys during systemic inflammation (n=8 mice per group). IVM revealed a reduced number of adherent and transmigrated neutrophils in the cremaster and kidney after HES 130/0.4 administration (n=8 mice per group). Flow chamber experiments showed that HES 130/0.4 significantly reduced chemokine-induced neutrophil arrest (n=4 mice per group). Furthermore, HES 130/0.4 significantly reduced the formation of platelet–neutrophil aggregates, and NET formation during systemic inflammation (n=8 mice per group). Conclusions Our findings suggest that HES 130/0.4 significantly reduces neutrophil–platelet aggregates, NET formation, chemokine-induced arrest, and transmigration of neutrophils under inflammatory conditions. [ABSTRACT FROM PUBLISHER]

Objective: Improvement of mucosal barrier function and reduction of bacterial translocation are important in the management of sepsis. The mechanisms that underlie the protective effects of colloids on the intestinal mucosal barrier are unclear. The study aims to investigate the effect of fluid resuscitation with hydroxyethyl starch (HES) 130/0.4 against intestinal mucosal barrier dysfunction in a rabbit model of sepsis. Materials and Methods: Thirty healthy rabbits were randomly and equally divided into a sham-operated control, a sepsis model, or a sepsis + HES treatment group. The sepsis model and sepsis + HES treatment groups were subjected to a modified colon ascendens stent peritonitis (CASP) procedure to induce sepsis. Four hours after the CASP procedure, fluid resuscitation was performed with 6% HES 130/0.4. Arterial and superior mesenteric vein blood samples were collected 4 and 8 h after the CASP procedure for blood gas analysis and measuring tumor necrosis factor-α, interleukin-10, and D-lactate levels. The rabbits were euthanized 8 h after CASP, and sections of the small intestine were stained to evaluate histopathological changes. Results: Respiratory rate and blood pressure were stable during the resuscitation period. Fluid resuscitation with 6% HES 130/0.4 alleviated pathological changes in the abdominal cavity, improved blood gas parameters and inflammatory mediator levels, decreased plasma D-lactate levels, and reduced intestinal mucosal injury compared with the non-treated sepsis model. Conclusions: Fluid resuscitation with 6% HES 130/0.4 protects against intestinal mucosal barrier dysfunction in rabbits with sepsis, possibly via mechanisms associated with improving intestinal oxygen metabolism and reducing the release of inflammatory mediators. [ABSTRACT FROM AUTHOR]

Abstract: The profile of an ideal volume substitution solution can be defined by volume effect and safety. The volume effect should be stable and reliable, offer a constant plateau effect and be easily controllable. Many in depth characteristics has been offered by recognized societies and includes: no tissue storage, no plasma accumulation, no influence on haemostasis, no influence on the immune system, no infectivity, no antigenicity, no allergenic potential, no proinflammatory properties, no toxicity, teratogenity or mutagenity, no influence on diagnostic tests, good compatibility with other medication, good tolerance, and complete elimination. Research has shown that it is possible to meet these objectives in the development of hydroxyethyl starches (HES) by optimizing the combination of concentration, the molecular weight, the degree and pattern of substitution. A new starch (HES 130/0.4) has therefore been developed. This new generation of HES offers the same volume effect and duration as the previous standard HES 200/0.5, yet with more favorable pharmacological characteristics and an improved safety profile. The following article is a collection of experts’ opinion from different recognized universities, hospitals and healthcare organizations about the evidence based clinical decisions when using Waxy-Maize HES 130/0.4 (Voluven®) in various clinical situations. [Copyright &y& Elsevier]

Objective: The bio-incompatibility of the cardiopulmonary bypass (CPB) circuit and the use of artificial colloids trigger massive defense reaction that involves endothelial cells and several blood cells: platelets, neutrophils, monocytes, red blood cells (RBC) and lymphocytes. Investigating the effects on RBC aggregation and endothelial cells activation, the present study addresses two different prime solutions commonly used in the clinical practice. Methods: RBC aggregation was measured by means of Laser-assisted Optical Rotation Cell Analyzer, in an in vitro study designed to mimic the human blood–material interactions during extracorporeal circulation. A clinical study investigating endothelial activation was conducted in 20 patients undergoing elective coronary bypass surgery, randomly assigned for CPB using two different priming solutions: HAES-steril 6% (HES 200/0.5) and Voluven 6% (HES 130/0.4). Results: Circulation trough a Chandler loop of HES–blood mixes altered significantly RBC aggregability. The use of HES 130/0.4 resulted in marked decrease in RBC aggregation (aggregation index (AI) before and after circulation was 23.5±3.8 and 18±2.9, respectively), no significant differences being found when compared with Ringer''s lactate group. The use of HES 200/0.5 resulted in better maintained RBC aggregation (AI 39.7±5.9 and 29.7±4.7 before and after circulation, respectively). The AI measured for the whole blood (control) sample was 61.9±4.9 before circulation, and 58.1±4 after. Markers of endothelial activation (von Willebrand factor (vWF), thrombomodulin (TM), tissue plasminogen activator (tPA) and E-selectin) significantly increased during CPB. Differences between HES treatment groups were evident post-bypass. While the markers of endothelial activation returned to baseline in HES 200/0.5 group, HES 130/0.4 was associated on the first post-operative day with further increase of vWF and tPA. Conclusion: RBC aggregation significantly drooped as consequence of blood dilution and blood–material interaction. We reason that low RBC aggregation added to plasma viscosity reduction and non-physiologic flow conditions during extracorporeal circulation are important factors contributing to loss of shear stress at the venous endothelial wall. The loss of shear stress triggers complex signaling leading to endothelial activation. Additional fundamental research is needed in order to verify the hypothesis introduced by the present study. Characterizing the impact of rheologic parameters on endothelial function could prove to be valuable in patients undergoing CPB. [Copyright &y& Elsevier]

Objective: Improvement of mucosal barrier function and reduction of bacterial translocation are important in the management of sepsis. The mechanisms that underlie the protective effects of colloids on the intestinal mucosal barrier are unclear. The study aims to investigate the effect of fluid resuscitation with hydroxyethyl starch (HES) 130/0.4 against intestinal mucosal barrier dysfunction in a rabbit model of sepsis., Materials and Methods: Thirty healthy rabbits were randomly and equally divided into a sham-operated control, a sepsis model, or a sepsis + HES treatment group. The sepsis model and sepsis + HES treatment groups were subjected to a modified colon ascendens stent peritonitis (CASP) procedure to induce sepsis. Four hours after the CASP procedure, fluid resuscitation was performed with 6% HES 130/0.4. Arterial and superior mesenteric vein blood samples were collected 4 and 8 h after the CASP procedure for blood gas analysis and measuring tumor necrosis factor-α, interleukin-10, and D-lactate levels. The rabbits were euthanized 8 h after CASP, and sections of the small intestine were stained to evaluate histopathological changes., Results: Respiratory rate and blood pressure were stable during the resuscitation period. Fluid resuscitation with 6% HES 130/0.4 alleviated pathological changes in the abdominal cavity, improved blood gas parameters and inflammatory mediator levels, decreased plasma D-lactate levels, and reduced intestinal mucosal injury compared with the non-treated sepsis model., Conclusions: Fluid resuscitation with 6% HES 130/0.4 protects against intestinal mucosal barrier dysfunction in rabbits with sepsis, possibly via mechanisms associated with improving intestinal oxygen metabolism and reducing the release of inflammatory mediators.