Limiting calcium overload after cardiac arrest: The role of human albumin in controlled automated reperfusion of the whole body.

BACKGROUND: Regarding the overall inadequate results after cardiopulmonary resuscitation, the development of new treatment concepts is urgently needed. Controlled Automated Reperfusion of the whoLe body (CARL) represents a therapy bundle to control the conditions of reperfusion and the composition of the reperfusate after cardiac arrest (CA). The aim of this study was to investigate the plasma expander's role in the CARL priming solution and examine its mechanism of action. METHODS: Viscosity, osmolality, colloid osmotic pressure (COP), pH and calcium binding of different priming solutions were measured in vitro and compared to in vivo data. N = 16 pigs were allocated to receive CARL following 20 min of untreated CA with either human albumin 20% (HA, N = 8) or gelatin polysuccinate 4% (GP, N = 8). Blood gas analyses were performed during the first hour of reperfusion and catecholamine and fluid requirements were recorded. Neurological outcome was assessed by neurological deficit scoring (NDS) on the seventh day. RESULTS: In vitro, addition of HA to the CARL priming solution resulted in higher COP and higher calcium-binding than GP. In vivo, treatment with HA led to greater reduction of ionized calcium and higher extracorporeal flows within the first 30 min of reperfusion with no difference in catecholamine support and fluid requirement. Seven-day survival of 75% with no difference in NDS was observed in both groups. CONCLUSIONS: Our data show that the plasma expander in the CARL priming solution has a significant effect on the initial reperfusate and can potentially influence the course of resuscitation. However, seven-day survival and NDS did not differ between groups.

Lactate versus acetate buffered intravenous crystalloid solutions: a scoping review.

BACKGROUND: Buffered crystalloid solutions are increasingly recommended as first-line intravenous resuscitation fluids. However, guidelines do not distinguish between the different types of buffered solutions. The aim of this scoping review was to assess the evidence on the use of lactate- vs acetate-buffered crystalloid solutions and their potential benefits and harms. METHODS: We conducted this scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. We searched PubMed, Embase, Epistemonikos, and the Cochrane Library for studies assessing the effect of lactate- vs acetate-buffered crystalloid solutions on any outcome in adult hospitalised patients. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We included a total of 29 studies, 25 of which were clinical trials and four were observational studies. Most studies were conducted in surgical settings and indications for use were poorly described. The most commonly administered solutions were Ringer's lactate vs Ringer's acetate or Plasma-Lyte™. Outcomes included acid/base and electrolyte status; haemodynamic variables; and markers of renal and liver function, metabolism, and coagulation. Only a few studies reported patient-centred outcomes. Overall, the data provided no firm evidence for benefit or harm of either solution, and the quantity and quality of evidence were low. CONCLUSIONS: The quantity and quality of evidence on the use of different buffered crystalloid intravenous solutions were low, data were derived primarily from surgical settings, and patient-important outcomes were rarely reported; thus, the balance between benefits and harms between these solutions is largely unknown.

Study on the protection of dextran on erythrocytes during drug loading.

In comparison to other carriers, erythrocytes (red blood cells, RBCs) hold the advantages of unmatched long circulation, biocompatibility and biodegradability. However, because of the defects in RBCs carriers caused by the drug loading process, the biological activities of drug-loaded RBCs are worse than those of natural RBCs (NRBCs). We aim to study the protective effect of dextran on the activity of drug-loaded RBCs. Different molecular weights of dextran were selected and added to a hypotonic drug solution to prepare drug-loaded RBCs by the hypotonic preswelling method. Water-soluble betamethasone sodium phosphate (BSP) and fat-soluble artesunate (AS) were selected as model drugs. The results showed that the addition of dextran with a molecular weight of 40 kDa and a concentration of 10 % could significantly increase the Na+/K+-ATPase activity, improve the drug loading amount and lower the phosphatidylserine eversion rate. Moreover, it maintained a similar osmotic fragility to NRBCs and exhibited no effect on the morphological structure of drug-loaded RBCs. Laser confocal results showed tight covering of dextran over RBCs, which could explain the protective effects. The addition of dextran increased the activity of drug-loaded RBCs without affecting their in vivo circulation (at least nine days). In conclusion, 10 % dextran with a weight of 40 kDa displayed a significant protective effect on the bioactivity of drug-loaded RBCs, which could be expected to be a better way to facilitate hydrophobic and hydrophilic drug loading by RBCs.

Population-based volume kinetics of crystalloids and colloids in healthy volunteers.

We characterized the volume kinetics of crystalloid solutions (Ringer's lactate solution and 5% dextrose water) and colloid solutions (6% tetrastarch and 10% pentastarch) by nonlinear mixed-effects modeling in healthy volunteers. We also assessed whether the bioelectrical impedance analysis parameters are significant covariates for volume kinetic parameters. Twelve male volunteers were randomly allocated to four groups, and each group received the four fluid solutions in specified sequences, separated by 1-week intervals to avoid any carryover effects. Volunteers received 40 ml/kg Ringer's lactate solution, 20 ml/kg 5% dextrose water, 1000 ml 6% tetrastarch, and 1000 ml 10% pentastarch over 1 h. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. Bioelectrical impedance spectroscopy (BIS, INBODY S10, InBody CO., LTD, Seoul, Korea) was also carried out at preset time points. In total, 671 hemoglobin-derived plasma dilution data points were used to determine the volume kinetic characteristics of each fluid. The changes in plasma dilution induced by administration of crystalloid and colloid solutions were well-described by the two-volume and one-volume models, respectively. Extracellular water was a significant covariate for the peripheral volume of distribution at baseline in the volume kinetic model of Ringer's lactate solution. When the same amount was administered, the colloid solutions had ~4 times more plasma expansion effect than did the crystalloid solutions. Starches with larger molecular weights maintained the volume expansion effect longer than those with smaller molecular weights.

Resuscitation Fluid with Drag Reducing Polymer Enhances Cerebral Microcirculation and Tissue Oxygenation After Traumatic Brain Injury Complicated by Hemorrhagic Shock.

Traumatic brain injury (TBI) is frequently accompanied by hemorrhagic shock (HS) which significantly worsens morbidity and mortality. Existing resuscitation fluids (RF) for volume expansion inadequately mitigate impaired microvascular cerebral blood flow (mvCBF) and hypoxia after TBI/HS. We hypothesized that nanomolar quantities of drag reducing polymers in resuscitation fluid (DRP-RF), would improve mvCBF by rheological modulation of hemodynamics. METHODS: TBI was induced in rats by fluid percussion (1.5 atm, 50 ms) followed by controlled hemorrhage to a mean arterial pressure (MAP) = 40 mmHg. DRP-RF or lactated Ringer (LR-RF) was infused to MAP of 60 mmHg for 1 h (pre-hospital), followed by blood re-infusion to a MAP = 70 mmHg (hospital). Temperature, MAP, blood gases and electrolytes were monitored. In vivo 2-photon laser scanning microscopy was used to monitor microvascular blood flow, hypoxia (NADH) and necrosis (i.v. propidium iodide) for 5 h after TBI/HS followed by MRI for CBF and lesion volume. RESULTS: TBI/HS compromised brain microvascular flow leading to capillary microthrombosis, tissue hypoxia and neuronal necrosis. DRP-RF compared to LR-RF reduced microthrombosis, restored collapsed capillary flow and improved mvCBF (82 ± 9.7% vs. 62 ± 9.7%, respectively, p < 0.05, n = 10). DRP-RF vs LR-RF decreased tissue hypoxia (77 ± 8.2% vs. 60 ± 10.5%, p < 0.05), and neuronal necrosis (21 ± 7.2% vs. 36 ± 7.3%, respectively, p < 0.05). MRI showed reduced lesion volumes with DRP-RF. CONCLUSIONS: DRP-RF effectively restores mvCBF, reduces hypoxia and protects neurons compared to conventional volume expansion with LR-RF after TBI/HS.

Acid/base alterations during major abdominal surgery: 6% hydroxyethyl starch infusion versus 5% albumin.

BACKGROUND: To compare the effects of intraoperative infusions of balanced electrolyte solution (BES)-based hydroxyethyl starch (HES) and saline-based albumin on metabolic acidosis and acid/base changes during major abdominal surgery conducted using Stewart's approach. METHODS: Forty patients, aged 20-65 years, undergoing major abdominal surgery, were randomly assigned to the HES group (n = 20; received 500 ml of BES-based 6% HES 130/0.4) or the albumin group (n = 20; received 500 ml of normal saline-based 5% albumin). Acid-base parameters were measured and calculated using results obtained from arterial blood samples taken after anesthesia induction (T1), 2 hours after surgery commencement (T2), immediately after surgery (T3), and 1 hour after arriving at a postanesthetic care unit (T4). RESULTS: Arterial pH in the HES group was significantly higher than that in the albumin group at T3 (7.40 ± 0.04 vs. 7.38 ± 0.04, P = 0.043), and pH values exhibited significant intergroup difference over time (P = 0.002). Arterial pH was significantly lower at T3 and T4 in the HES group and at T2, T3, and T4 in the albumin group than at T1. Apparent strong ion difference (SIDa) was significantly lower at T2, T3, and T4 than at T1 in both groups. Total plasma weak nonvolatile acid (ATOT) was significantly lower in the HES group than in the albumin group at T2, T3 and T4 and exhibited a significant intergroup difference over time (P < 0.001). CONCLUSIONS: BES-based 6% HES infusion was associated with lower arterial pH values at the end of surgery than saline-based 5% albumin infusion, but neither colloid caused clinically significant metabolic acidosis (defined as an arterial pH < 7.35).

Synthesized tissue-equivalent dielectric phantoms using salt and polyvinylpyrrolidone solutions.

PURPOSE: To explore the use of polyvinylpyrrolidone (PVP) for simulated materials with tissue-equivalent dielectric properties. METHODS: PVP and salt were used to control, respectively, relative permittivity and electrical conductivity in a collection of 63 samples with a range of solute concentrations. Their dielectric properties were measured with a commercial probe and fitted to a 3D polynomial in order to establish an empirical recipe. The material's thermal properties and MR spectra were measured. RESULTS: The empirical polynomial recipe (available at https://www.amri.ninds.nih.gov/cgi-bin/phantomrecipe) provides the PVP and salt concentrations required for dielectric materials with permittivity and electrical conductivity values between approximately 45 and 78, and 0.1 to 2 siemens per meter, respectively, from 50 MHz to 4.5 GHz. The second- (solute concentrations) and seventh- (frequency) order polynomial recipe provided less than 2.5% relative error between the measured and target properties. PVP side peaks in the spectra were minor and unaffected by temperature changes. CONCLUSION: PVP-based phantoms are easy to prepare and nontoxic, and their semitransparency makes air bubbles easy to identify. The polymer can be used to create simulated material with a range of dielectric properties, negligible spectral side peaks, and long T2 relaxation time, which are favorable in many MR applications. Magn Reson Med 80:413-419, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A comparison of balanced and unbalanced crystalloid solutions in surgery patient outcomes.

INTRODUCTION: The objective of this study was to evaluate adverse patient outcomes associated with the choice of intravenous fluid administered during general anaesthesia. METHODS: This study was a retrospective chart review of vascular surgery patients at a Canadian tertiary care hospital. Patients were separated into three groups: those who were intraoperatively administered normal saline (NS), balanced crystalloids, or a combination of both solutions. Multivariate analysis was performed to determine association between volume of each fluid type administered and adverse outcomes including in-hospital mortality, prolonged intensive care unit admission, vasopressor requirement, ventilator requirement, hemodialysis requirement, and a composite endpoint of any of these adverse events occurring. RESULTS: Overall, 796 vascular surgery patients were included in the analysis. There were 425 patients who received balanced crystalloids, 158 patients who received NS, and 213 patients received both balanced crystalloids and NS. Groups were similar in age (P=0.06), but varied in gender (P<0.001) and overall health (ASA≥2; P=0.027). The most common adverse event was ventilator requirement (NS: 27.9%, balanced: 7.5%, both: 38.0%; P<0.001). Mortality was lowest in the group that received balanced fluids (NS: 12.0%, balanced: 5.9%, both: 10.8%; P=0.018). Patients who were administered NS or both fluids were more likely to reach the composite endpoint than patients receiving balanced crystalloid alone. CONCLUSION: The administration of an unbalanced crystalloid solution was associated with poor patient outcomes in our study population.

An Investigation Into the Effects of In Vitro Dilution With Different Colloid Resuscitation Fluids on Clot Microstructure Formation.

BACKGROUND: Balancing the beneficial effects of resuscitation fluids against their detrimental effect on hemostasis is an important clinical issue. We aim to compare the in vitro effects of 3 different colloid resuscitation fluids (4.5% albumin, hydroxyethyl starch [Voluven 6%], and gelatin [Geloplasma]) on clot microstructure formation using a novel viscoelastic technique, the gel point. This novel hemorheologic technique measures the biophysical properties of the clot and provides an assessment of clot microstructure from its viscoelastic properties. Importantly, in contrast to many assays in routine clinical use, the measurement is performed using unadulterated whole blood in a near-patient setting and provides rapid assessment of coagulation. We hypothesized that different colloids will have a lesser or greater detrimental effect on clot microstructure formation when compared against each other. METHODS: Healthy volunteers were recruited into the study (n = 104), and a 20-mL sample of whole blood was obtained. Each volunteer was assigned to 1 of the 3 fluids, and the sample was diluted to 1 of 5 different dilutions (baseline, 10%, 20%, 40%, and 60%). The blood was tested using the gel point technique, which measures clot mechanical strength and quantifies clot microstructure (df) at the incipient stages of fibrin formation. RESULTS: df and clot mechanical strength decrease with progressive dilution for all 3 fluids. A significant reduction in df from baseline was recorded at dilutions of 20% for albumin (P < .0001), 40% for starch (P < .0001), and 60% for gelatin (P < .0001). We also observed significant differences, in terms of df, when comparing the different types of colloid (P < .0001). We found that albumin dilution produced the largest changes in clot microstructure, providing the lowest values of df (= 1.41 ± 0.061 at 60% dilution) compared with starch (1.52 ± 0.081) and gelatin (1.58 ± 0.063). CONCLUSIONS: We show that dilution with all 3 fluids has a significant effect on coagulation at even relatively low dilution volumes (20% and 40%). Furthermore, we quantify, using a novel viscoelastic technique, how the physiochemical properties of the 3 colloids exert individual changes on clot microstructure.

Blood Products, Crystalloids, and Rapid Infusion: An Experimental Study.

BACKGROUND: Electromagnetic coil overheating, deformation, occlusion, and rupture during rapid infuser use have been previously reported. Although the etiology is unclear, prolonged machine use and reconstitution of citrated blood components with crystalloid solutions in the reservoir have been implicated. Lactated Ringer's (LR) solution is of particular concern as a diluent because of its calcium content. We sought to reproduce this failure mode using different infusion rates and different combinations of fluids for blood product reconstitution in the reservoir. We also introduced calcium chloride (CaCl2) to the mix to determine its role in macroscopic clot formation. METHODS: In this in vitro study, we conducted 2 series of experiments using the Belmont FMS 2000 rapid infuser and a reservoir. In series I, we submitted a mix of 1 U fresh thawed plasma (FTP) and 1 U red blood cells (RBC) with 500 mL of LR solution, normal saline, Plasma-Lyte A, or albumin 5% to a specific pump flow sequence. If neither a pump failure mode or self-shutoff (primary outcome) nor macroscopic clot (secondary outcome) was observed during a pump flow sequence, the sequences were repeated after first adding an additional 500 mL of the initially used crystalloid or albumin and then CaCl2 beginning with 200 mg and up to 1 g to the reservoir. In series II, 7 different crystalloid-blood product combinations were tested by using a variety of pump flow sequences with the same end points. Descriptive statistics and analysis of variance were used, and data were reported as means ± SD. RESULTS: We did not observe a Belmont pump failure mode (coil deformation, occlusion, or rupture) as previously described. In series I, the addition of CaCl2 200 mg resulted in macroscopic clots in 9 of 10 experiments (95% confidence interval, 0.55-0.99). The time to clot formation was 9.1 ± 2.3 minutes (99% confidence interval, 6.74-11.46) and did not differ between solutions used for component reconstitution. In series II, adding variable amounts of CaCl2 to 4 different combinations of FTP/RBC with Plasma-Lyte A or LR solution led to clot formation. The use of only FTP in 2 experiments with either LR solution or normal saline resulted in formation of a fibrin clot. In 1 experiment of LR solution mixed with RBCs alone, no clot was observed even after addition of 1 g CaCl2. After the observation of clot in the reservoir, the fluid empty alarm occurred once in series I, the overheating alarm occurred once in series II, and the high-pressure alarms occurred 3 times in each series, all accompanied by self-shutoff. CONCLUSIONS: In this in vitro study, we were unable to reproduce the failure mode characterized by coil overheating, deformation, and rupture previously reported with use of the FMS 2000. Addition of CaCl2 in the range of 200 mg caused macroscopic coagulation in the reservoir when added to crystalloids or albumin mixed with different combinations of blood products containing FTP.

Characterization and physiological effect of tapioca maltodextrin colloid plasma expander in hemorrhagic shock and resuscitation model.

Plasma expanders (PEs) are administered fluids to replace blood volume when massive blood loss has occured. Maltodextrin from tapioca starch was selected as a study candidate to prepare a colloid PE due to an uncomplicated production process. The formulations of mixture between tapioca maltodextrin and 0.9 % sodium chloride solution were prepared and then characterized. This was to investigate the effects of a dextrose equivalent (DE) and the concentration on the physical properties. Storage stability of each formulation was also determined and compared with clinically used PE [6 % hydroxyethyl starch (HES), 130/0.4]. The effects on the circulatory system in hamsters with hemorrhagic shock and resuscitation using prepared PE were also investigated. The results showed that low DE value led to high retrogradation, turbidity and viscosity but low colloid osmotic pressure and poor solubility. Among the prepared solutions, tapioca maltodextrin with DE6 at 10 % w/v concentration had comparable properties with 6 % HES 130/0.4. Animals resuscitated with 10 % DE6 PE had improved mean arterial blood pressure similar to those resuscitated with 6 % HES 130/0.4. However, several parameters in animals resuscitated with 10 % DE6 PE were lower than those resuscitated with 6 % HES 130/0.4, i.e., heart rate, functional capillary density. Therefore, if using tapioca maltodextrin for PE, some properties have to be considered and efficiently optimized.

Physicochemical properties and responses in microcirculation of native tapioca starch-based plasma expander.

Plasma expanders (PEs) such as hydroxyethyl strach are widely used for volume replacement. The plantation and production of tapioca in Thailand is abundant which may provide a new source for PEs starch with novel properties. This work investigated the properties and circulatory effects of native tapioca starch-based PE (TPE). Various formulations of mixture between native tapioca starch and 0.9% sodium chloride solution were prepared and characterized in order to obtain the proper physicochemical and rheological properties. About 1% concentration by weight per volume of TPE was compared with 6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride (HES130/0.4) using an acute hemodilution by 40% of blood volume in an animal protocol. TPE had higher turbidity and viscosity but lower colloid osmotic pressure compared with HES 130/0.4. The in vivo study demonstrated that Golden Syrian hamsters hemodiluted with TPE maintained a mean arterial blood pressure and no significant difference compared to HES 130/0.4. The arterial vasodilation and functional capillary density in the animals hemodiluted with TPE had higher values than in the animals hemodiluted with HES 130/0.4. Although the in vivo study reported positive results using this native tapioca starch-based PE, the product needs work to improve some of its physiochemical properties.

New insights into in vitro amyloidogenic properties of human serum albumin suggest considerations for therapeutic precautions.

Amyloid aggregates display striking features of detergent stability and self-seeding. Human serum albumin (HSA), a preferred drug-carrier molecule, can also aggregate in vitro. So far, key amyloid properties of stability against ionic detergents and self-seeding, are unclear for HSA aggregates. Precautions against amyloid contamination would be required if HSA aggregates were self-seeding. Here, we show that HSA aggregates display detergent sarkosyl stability and have self-seeding potential. HSA dimer is preferable for clinical applications due to its longer retention in circulation and lesser oedema owing to its larger molecular size. Here, HSA was homodimerized via free cysteine-34, without any potentially immunogenic cross-linkers that are usually pre-requisite for homodimerization. Alike the monomer, HSA dimers also aggregated as amyloid, necessitating precautions while using for therapeutics.

Modified hydroxyethyl starch protects cells from oxidative damage.

This article describes the synthesis of novel starch-antioxidant conjugates, which show great potential for biomedical applications to protect cells from oxidative damage. These conjugates were synthesized by the modification of a hydroxyethyl starch (molecular weight=200,000g/mol) with various sterically hindered phenols that differ in radical scavenging activity. They possess substantial radical scavenging activity toward a model free radical. It was found that the polymer conjugate conformation depends on the antioxidant structure and degree of substitution. We constructed the complete conformational phase behavior for the polymers with increasing degrees of substitution from small-angle neutron scattering data. It was observed that the conjugate conformation changes are the result of water shifting from a thermodynamically favorable solvent to an unfavorable one, a process that then leads to compaction of the conjugate. We selected the conjugates that possess high substitution degree but still exhibit coil conformation for biological studies. The high efficiency of the conjugates was confirmed by different in vitro (hypotonic hemolysis of erythrocytes/osmotic resistance of erythrocytes and the change of [Ca(2+)]i inside freshly isolated cardiomyocytes) and in vivo (acute hemorrhage/massive blood loss) methods.

Molecular weight and molar substitution are more important in HES-induced renal impairment than concentration after hemorrhagic and septic shock.

BACKGROUND: Clinical studies have raised concerns about the safety of 6% hydroxyethylstarch (HES) 130/0.42, but the pathomechanisms of this renal impairment remain unknown. To evaluate the effects of different HES concentrations, molar substitutions and molecular weights in HES-induced renal impairment, we used a porcine two-hit model that combined haemorrhagic and septic shock. METHODS: We conducted a prospective, randomised, double-blinded, controlled study in a university animal laboratory. Thirty anaesthetised and ventilated pigs were randomised to receive volume replacement therapy using 6% HES130/0.42, 6% HES200/0.5, 10% HES130/0.42 or 10% HES200/0.5, all dissolved in 0.9% NaCl rather than 0.9% NaCl alone. First, we bled the animals until they reached half of their baseline mean arterial pressure (MAP) for 45 minutes followed by fluid resuscitation. As a second hit, sepsis was induced using an Escherichia coli-laden clot 6 hours after haemorrhagic shock. Volume resuscitation started with a delay of two hours and a central venous pressure goal of 12 mmHg. RESULTS: At the end of the study, the groups showed no difference in cardiac output or MAP, but the volume balance (mL/kg BW) was significantly higher in the 0.9% NaCl group (346±90; P≤0.05) than in the other groups (6% HES130, 125±26; 6% HES200, 105±15; 10% HES130, 114±17; 10% HES200, 96±23). Creatinine clearance (mL/min) was significantly lower in the 6% HES200 (26±33) and 10% HES200 (15±18) groups compared to the 0.9% NaCl group (104±46; P≤0.05) but not in the HES 130 formulations (6% HES130: 64±51; 10% HES130: 58±38) at the end of the study. CONCLUSION: In this porcine two-hit shock model, treatment with 0.9% NaCl, HES 130/0.42 or HES 200/0.5 led to a similar maintenance of haemodynamic values. Despite this similar maintenance of the haemodynamic values, volume replacement with 6% and 10% HES 200/0.5 led to an accumulation of HES, higher colloid osmotic pressure and significantly reduced renal function after haemorrhagic and septic shock. These facts support the presumption that not the concentration but the degree of substitution and the molecular weight play a decisive role in HES-induced renal impairment.

Is hydroxyethyl starch necessary for sedimentation of bone marrow?

Hydroxyethyl starch (HES) is used to separate hematopoietic progenitor cells after bone marrow (BM) collection from red blood cells. The aims were to study alternatives for HAES-steril (200 kDa; not available anymore) and to optimize the sedimentation process. Using WBC-enriched product (10 × 10(9) WBC/L), instead of BM, sedimentation at 10% hematocrit using final 0.6 or 0.39% Voluven (130 kDa) or without HES appeared to be good alternatives for 0.6% HAES-steril. MNC recovery >80% and RBC depletion >90% was reached. Optimal sedimentation was reached using 110-140 mL volume. Centrifugation appeared not suitable for sedimentation. Additional testing with BM might be necessary to confirm these results.

In vitro biocompatibility and cellular interactions of a chitosan/dextran-based hydrogel for postsurgical adhesion prevention.

In this paper, we report the in vitro biocompatibility and cellular interactions of a chitosan/dextran-based (CD) hydrogel and its components as determined by mutagenicity, cytotoxicity, cytokine/chemokine response, and wound healing assays. The CD hydrogel, developed for postsurgical adhesion prevention in ear, nose, and throat surgeries, was shown by previously published experiments in animal and human trials to be effective. The hydrogel was synthesized from the reaction between succinyl chitosan (SC) and oxidized dextran (DA). Cytotoxicity was assessed in an xCELLigence system and cytokine/chemokine responses were measured by ELISA in human macrophage, nasopharyngeal epithelial, and dermal fibroblast cells. A wound healing model utilized nasopharyngeal epithelial cells. CD hydrogel and DA were nonmutagenic in the Ames test. CD hydrogel showed moderate cytotoxicity for the cell lines, DA being the cytotoxic component. Some inhibition of wound healing occurred due to the cytotoxic nature of DA. Cells cultured with CD hydrogel showed no increase in TNF-α, IL-10, and IL-8 levels. It is hypothesized that the cytotoxicity of DA is moderated when reacted with SC and that CD hydrogel inhibits unwanted fibroblastic invasion preventing scarring and adhesions. Together with the previously published human and animal trial data, the results indicate CD hydrogel is biocompatible in the setting of endoscopic sinus surgery. This work represents the first study of CD hydrogel with human cell lines and provides essential information for its future application in biomedicine.

Blood substitutes.

The toxic side effects of early generations of red blood cell substitutes have stimulated development of more safe and efficacious high-molecular-weight polymerized hemoglobins, poly(ethylene glycol)-conjugated hemoglobins, and vesicle-encapsulated hemoglobins. Unfortunately, the high colloid osmotic pressure and blood plasma viscosity of these new-generation materials limit their application to blood concentrations that, in general, are not sufficient for full restoration of oxygen-carrying and -delivery capacity. However, these materials may serve as oxygen therapeutics for treating tissues affected by ischemia and trauma, particularly when the therapeutics are coformulated with antioxidants. These new oxygen therapeutics also possess additional beneficial effects owing to their optimal plasma expansion properties, which induce systemic supraperfusion that increases endothelial nitric oxide production and improves tissue washout of metabolic wastes, further contributing to their therapeutic role.