Foreign Surfaces Research Articles

Oxidative Desorption Behavior of Sulfur Species from Pt and Pt Based Alloy Single Crystal Surfaces

Pt and Pt-based alloys are the most widely used electrocatalyst for polymer electrolyte membrane fuel cells (PEMFCs) because of their very high hydrogen oxidation and oxygen reduction activities. However, trace amounts of S species in hydrogen fuel and air, especially in long tunnels and volcanic areas, often strongly adsorb on the Pt and Pt-based alloy surfaces, resulting in reduced electrochemically active surface area (S poisoning). Thus, understanding of adsorption/desorption behavior of S species at Pt and Pt-based alloy surfaces is very important to mitigate such S poisoning. In the present study, oxidative desorption behavior of S species from well-defined Pt and Pt-based alloy single crystal surfaces in acidic aqueous solutions were studied by electrochemical measurements, x-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculation.Pt and Pt-based alloy single crystal surfaces were annealed by induction heating method [1, 2, 3] at various temperatures for 1 h under the flowing of Ar and H2 mixed gas, followed by cooling under the Ar and H2 flow for 7 min. The surfaces were then immersed in an aqueous solution of 1 mM Na2S for 1 h to yield S-adsorbed surfaces. After rinsing with water, electrochemical measurements were carried out in an aqueous solution of 0.1 M HClO4, followed by XPS measurements.Bare Pt and Pt-based alloy single crystal surfaces showed characteristic current responses corresponding to adsorption/desorption of hydrogen and hydroxyl species as previously reported. After immersing in the 1 mM Na2S solution, those characteristic current responses completely disappeared due to the blocking of adsorbed elemental S species as evidenced by XPS. However, those characteristic current responses gradually recovered by repeating the potential cycles in the potential range between 0 V and 0.8 V or more positive, due to the oxidative desorption of S species. The recovery factor significantly depends on the face orientation, alloying foreign metal and surface modification. Among the Pt(111), Pt(110) and Pt(100) surfaces, Pt(111) surface showed the highest S oxidation capability. The S oxidation capability was further accelerated by alloying with several transition metals and coating with metal oxides. The details will be discussed.

Iron Oxide Nanoparticles as Promising Antibacterial Agents of New Generation.

Antimicrobial resistance (AMR) is growing into a major public health crisis worldwide. The reducing alternatives to conventional agents starve for novel antimicrobial agents. Due to their unique magnetic properties and excellent biocompatibility, iron oxide nanoparticles (IONPs) are the most preferable nanomaterials in biomedicine, including antibacterial therapy, primarily through reactive oxygen species (ROS) production. IONP characteristics, including their size, shape, surface charge, and superparamagnetism, influence their biodistribution and antibacterial activity. External magnetic fields, foreign metal doping, and surface, size, and shape modification improve the antibacterial effect of IONPs. Despite a few disadvantages, IONPs are expected to be promising antibacterial agents of a new generation.

The influence of membrane fiber arrangement on gas exchange in blood oxygenators: A combined numerical and experimental analysis

Oxygenators take over lung function in the event of severe lung injuries by exchanging gas into the blood stream using hollow fiber membrane mats. A central limitation of oxygenators is their large foreign surface area and priming volume, which cause blood damage.Thus, gas exchange efficiency needs to be improved through an understanding of the interaction between fiber arrangement and blood flow directions. This has only been investigated in two dimensional or simplified non-realistic fiber bundles. The aim of this study was to quantify gas exchange in realistic 3D fiber bundles.We performed three dimensional micro scale CFD simulations of different realistic fiber arrangements and flow directions that we validated in corresponding test oxygenators using porcine blood.Fiber-configurations influence gas transfer by factor 2, with highest transfer rates for blood flowing in circumferential direction, and lowest for longitudinal direction in wound oxygenators. The CFD model correlates with the experiments with an R2 = 0.88.For the first time, the configuration of realistic 3D fiber bundles was proven to strongly influence gas transfer in oxygenators, in simulations and experiments. The CFD model serves for investigation of further configurations and to derive transfer coefficients for full scale oxygenators.

Immunofluorescence Protocol for Characterization of Platelet and Leukocyte Binding in Extracorporeal Membrane Oxygenation (ECMO) Circuits.

The continuous contact between blood and the foreign surface of the extracorporeal membrane oxygenation (ECMO) circuit contributes to hemostatic, inflammatory, and other physiological disturbances observed during ECMO. Although previous studies have extensively investigated blood samples from patients on ECMO, cell adsorption to the ECMO circuit as an additional factor that could potentially influence clinical outcomes, has largely been overlooked. Here we provide a detailed immunofluorescence (IF) protocol designed to characterize cellular binding on ECMO circuits collected from patients. Extracorporeal membrane oxygenation circuits were collected from three pediatric patients and an albumin primed-only ECMO circuit was used as control. Circuit samples from five different sites within each ECMO circuit were collected and processed for the IF protocol. CD14 and CD42a antibodies were used to identify platelets and leukocytes bound to each ECMO circuit sample and images captured using inverted fluorescence microscopy. The protocol enables the comprehensive characterization of platelet and leukocyte binding to ECMO circuits collected from patients, which could in turn extend our knowledge of the characteristics of circuit binding and may provide guidance for improved ECMO circuit design.

Factor XII contact activation can be prevented by targeting 2 unique patches in its epidermal growth factor-like 1 domain with a nanobody

BackgroundFactor (F)XII triggers contact activation by binding to foreign surfaces, with the epidermal growth factor-like 1 (EGF-1) domain being the primary binding site. Blocking FXII surface-binding might hold therapeutic value to prevent medical device–induced thrombosis. ObjectivesTo unravel and prevent EGF-1–mediated FXII surface-binding with a variable domain of heavy chain–only antibody (VHH). MethodsFXII variants with glutamine substitutions of 2 positively charged amino acid patches within the EGF-1 domain were created. Their role in FXII contact activation was assessed using kaolin pull-down experiments, amidolytic activity assays, and clotting assays. FXII EGF-1 domain–specific VHHs were raised to inhibit EGF-1–mediated FXII contact activation while preserving quiescence. ResultsTwo unique, positively charged patches in the EGF-1 domain were identified (upstream, 73K74K76K78H81K82H; downstream, 87K113K). Neutralizing the charge of both patches led to a 99% reduction in FXII kaolin binding, subsequent decrease in autoactivation of 94%, and prolongation of clot formation in activated partial thromboplastin time assays from 36 (±2) to 223 (±13) seconds. Three FXII EGF-1–specific VHHs were developed that are capable of inhibiting kaolin binding and subsequent contact system activation in plasma. The most effective VHH “F2” binds the positively charged patches and thereby dose-dependently extends activated partial thromboplastin time clotting times from 29 (±2) to 43 (±3) seconds without disrupting FXII quiescence. ConclusionThe 2 unique, positively charged patches in FXII EGF-1 cooperatively mediate FXII surface-binding, making both patches crucial for contact activation. Targeting these with FXII EGF-1–specific VHHs can exclusively decrease FXII surface-binding and subsequent contact activation, while preserving zymogen quiescence. These patches thus have potential as druggable targets in preventing medical device–induced thrombosis.

Designing an experimental method for assessing biocompatibility of circuit coatings using biomarkers for platelet activation during cardiopulmonary bypass.

Cardiopulmonary bypass is an essential component of cardiothoracic surgeries. However, significant complications such as systemic inflammatory response syndrome (SIRS) resulting from cardiopulmonary bypass (CPB) are a common occurrence due to contact between circulating blood and foreign surfaces that leads to platelet activation. It is suggested that different available CPB circuit coatings can potentially reduce platelet activation. However, there have been no published evidence-based reports confirming these claims. In addition, there is no well-established protocol for studying platelet activation biomarkers during CPB in vitro in a laboratory setting. CPB was simulated in the laboratory using bovine blood in two different types of coated CPB circuits: Trillium® Biosurface by Medtronic, and XcoatingTM Surface by Terumo. Fresh bovine blood samples were collected and circulated through the CPB circuit following the standard protocol used in the operation rooms. Blood samples were then collected at 5min, 30min, and 55min during the circulation. Blood plasmas were separated and subjected to enzyme-linked immunosorbent assay to measure most established platelet activation markers P-selectin, Platelet Factor 4 (PF4), Glycoprotein IIb/IIIa (GPIIb/IIIa), and β-thromboglobulin (β-TG) at different time points. The biomarker values at 30min and 55min were compared to the base values at 5min for each type of CPB circuit. The results of the means from all measured biomarkers showed data measurements that indicated no significant variability within each coating. All collected data points fell within±2 SD of the means, which was considered acceptable variations across technical replicates. Conclusion: In this study, we were able to establish an in vitro protocol in the laboratory setting that is precise and reliable with minimum intra-variability. This established protocol will allow for future studies in which different coated CPB circuits can be compared for their effectiveness in blocking platelet activation during the CPB.

#2866 The CompAct-HD trial reports a persistent inflammatory profile in patients undergoing haemodialysis, acutely exacerbated with each treatment

Abstract Background and Aims Inflammation induced by haemodialysis (HD) treatment has been recognised for several decades. Despite significant advances in technology, there is evidence that incompatibility between the dialyser, a foreign surface, and the patients’ blood, results in activation of the immune system. With each session, blood-membrane interaction leads to a repetitive activation of the innate complement system and a subsequent inflammatory response. It is now widely acknowledged that the consequences of long-term inflammation include fibrosis and accelerated cardiovascular disease, a common cause of mortality in patients with renal failure. The aim of the CompAct-HD trial is to characterize complement activation and biomarker response to blood-membrane-circuit interaction during HD. Method For a single session, six timed intradialytic blood samples were collected from HD patients during standard treatment with ultrapure water and high flux “biocompatible” membranes. Complement activity potential was determined from timepoint 1 and inflammatory biomarkers from timepoints 2 to 6. Single time point samples were also collected from 7 healthy donors. Highly multiplexed assays enabled to determine 30 biomarkers of inflammation, including cytokines, chemokines, growth factors and complement proteins, from a single blood sample. Data analysis was performed using Microsoft® Excel Version 16.80 and GraphPad Prism 10.1.0. Results 354 patients were recruited from 8 dialysis units across Greater Manchester, UK. An interim analysis was performed on 150 HD patients receiving standard care as well as 7 healthy donors. Dialysis appears to generate an acute inflammatory response, that is, within 15 minutes of commencing treatment which does not appear to resolve by the end of the session. This heightened inflammatory state was observed in HD patients in comparison to healthy donors (Fig. 1) with most pronounced changes seen in cytokines IL-1β, IL-10, IL-12p40 and TNF-α during dialysis. Established markers such as IL-6 also showed a 6-fold increase at the 75th percentile. Similarly, an exaggerated intradialytic response was observed in complement proteins, including the terminal complement complex (TCC) C5b-9 and anaphylatoxin C5a with spikes of up to 7-fold and 10-fold respectively (Fig. 2). A session of HD was shown to cause a relative increase in complement proteins and inflammatory biomarkers. The magnitude of response seen in patients was variable (Fig. 3) with the greatest rise seen in the top quartile (above the Q3 boundary). Conclusion Our findings evidence a sharp inflammatory response to modern day HD treatment across a large cohort of dialysis patients. When compared to healthy donors, we observed heightened levels of inflammation in dialysis patients that is further exacerbated with each treatment session. This study shows that HD has a significant role to play in the chronic inflammatory state of patients with end stage renal failure. Furthermore, here we describe potential targets, in both cytokine and complement proteins, which could be the key to downregulation of inflammation. Using targeted therapeutics, we have an opportunity to deliver a more biocompatible treatment, improving patient outcomes.

Membrane supported liquid-liquid oxygenation for use in extracorporeal life support – Proof of principle

Chronic respiratory diseases are the third most frequent cause of death worldwide. However, the limited availability of transplantable organs led to an increased research effort in artificial lung systems. Current artificial lung systems use hollow fibre membrane-based oxygenators. Historic oxygenators using a direct liquid-gas or liquid-liquid interface outperformed todays hollow-fibre technology in terms of gas-transfer. However, these approaches were no longer pursued due to risk of embolization by gas or liquid droplet formation in the blood stream. The herein presented approach of a membrane-supported liquid-liquid oxygenator combines todays hollow-fibre technology with historic liquid-liquid approaches to achieve a stable interface without the risk of embolization but with the advantages of a higher gas-transfer and a decreasing foreign membrane surface of the oxygenator. Perfluoro-n-hexane was chosen as a hemocompatible carrier fluid for the presented liquid-liquid approach. In the proof-of-principle oxygenator, O2 and CO2 gas-transfers were measured to be 1.83 mmolO2 and 1.34 mmolCO2, respectively. No Perfluoro-n-hexane droplets were detected in the blood after the experiment. This study demonstrates the proof of principle of a new membrane-supported liquid-liquid oxygenator.

Validation of dot blot immunoassay for measurement of complement opsonization of nanoparticles

Complement plays a critical role in the immune response toward nanomaterials. The complement attack on a foreign surface results in the deposition of C3, assembly of C3 convertases, the release of anaphylatoxins C3a and C5a, and finally, the formation of membrane attack complex C5b-9. Various technologies can measure complement activation markers in the fluid phase, but measurements of surface C3 deposition are less common. Previously, we developed an ultracentrifugation-based dot blot immunoassay (DBI) to measure the deposition of C3 and other protein corona components on nanoparticles. Here, we validate the repeatability of the DBI and its correlation with pathway-specific and common fluid phase markers. Moreover, we discuss the advantages of DBI, such as cost-effectiveness and versatility, while addressing potential limitations. This study provides insights into complement activation at the nanosurface level, offering a valuable tool for nanomedicine researchers in the field.

Heterogeneous Nucleation Mechanism of Potassium Iodide on Graphene Surface in Water

In this work, molecular dynamic (MD) simulations are applied to investigate the heterogeneous nucleation mechanism of KI on a graphene surface in water. As graphene is immersed in water, it mainly affects the structure of interfacial water (the topmost water layer at the interface between the substance and water). To maximize the hydrogen bonding of water, the dissolved solutes tend to accumulate to form the aggregate at the graphene surface, which undoubtedly affects the nucleation pathways of solutes in water. In comparison with homogeneous nucleation, a lower barrier may be expected during the heterogeneous nucleation of KI on a graphene surface in water. Therefore, as the graphene is immersed in water, this facilitates solute nucleation. From this work, it may be derived that heterogeneous nucleation may be closely related to the geometric characteristics of foreign surfaces, especially their geometric shape.

Shock Wave-Activated Silver-Loaded Biopolymer Implant Coating Eliminates Staphylococcus epidermidis on the Surface and in the Surrounding of Implants.

Bacterial biofilms on foreign surfaces are considered a primary cause of implant-related infections, which are challenging to treat. A new implant coating was developed, containing anti-infective silver within a biocompatible polymer carrier substance. In addition to its passive effect on the implant surface, highly concentrated anti-infective silver can be released as needed via the application of high-energy shock waves. This intervention could be applied transcutaneously in a clinical setting without the need for additional surgery. We investigated the inhibition of biofilm formation and the effectiveness of eradication after activation of the coating via shock waves in an in vitro biofilm model using Staphylococcus epidermidis RP62A. This was performed via scanning electron microscopy and quantitative microbiology. Additionally, we examined the cytotoxicity of the new coating on normal human fibroblasts and Saos-2 osteoblast-like cells, depending on the silver concentration. All studies were compared to uncoated titanium surfaces Ti6Al4V and a conventional electroplated silver coating. Cytotoxicity toward normal human fibroblasts and Saos-2 osteoblast-like cells increased with higher silver content but remained tolerable at 6%. Compared to uncoated Ti6Al4V and the electroplated silver coating, the new coating with a silver content of 4% and 6% exhibited a significant reduction in adherent bacteria by a factor of approximately 1000. This was also evident via microscopic examination of the surface morphology of the biofilms. Furthermore, following shock wave activation, no bacteria were detectable on either the implant or in the surrounding fluid after a 24 h period.

Abstract 246: Consumptive Coagulopathy is Associated With Poor Neurological Outcome in Patients With Refractory VT/VF Cardiac Arrest Requiring Extracorporeal Cardiopulmonary Resuscitation

Introduction: Post cardiac arrest syndrome is associated with altered hemostasis. This is aggravated further by the foreign surface in the extracorporeal circuit leading to a coagulofibrinolytic imbalance. Aim: We examined the serial changes of consumptive coagulopathy markers and their association with neurologic outcomes. Methods: A single-center, retrospective cohort study of consecutive patients with VT/VF cardiac arrest meeting criteria for ECMO-facilitated resuscitation (ECPR) between December 2015 and January 2023 were included. Consumptive coagulopathy markers (INR, D-dimer, platelet count, antithrombin III and fibrinogen) were obtained after VA ECMO cannulation and serially on day 1, 2 and 3. We compared the coagulation profiles of patients who had a neurologically favorable outcome (defined as Cerebral Performance Categories (CPC) 1-2) and those with a neurologically unfavorable outcome (CPC 3-5). Results: Of 258 patients, 82 (32%) survived to hospital discharge. Of these, 87% (71/82) survived with favorable neurological outcome. Prolonged INR, elevated D-dimer levels and decreased ATIII levels were associated (p<0.05) with neurologically unfavorable survival and decreased over time (p<0.05)(Figure1). Platelet count and fibrinogen levels were not associated with neurological outcomes. In adjusted analysis (including age, lactate, CPR time and use of dual antiplatelet therapy), each point increase in the INR on day 1, 2 and 3 was associated with neurologically unfavorable survival (OR 4.4, p=0.01; OR 7.14, p=0.04; OR 8.5, p=0.03 respectively). Conclusion: Markers of consumptive coagulopathy with a prolonged INR are associated with unfavorable neurological outcome.

Surface electron modulation of metal oxide‐based electrochemical devices by surface additives—linking sensors and fuel cells

AbstractThe interaction between ambient oxygen and the metal oxide surface is central to various electrochemical devices. Solid oxide fuel cell cathodes and semiconducting metal oxide gas sensors are two prominent examples. Parallels between these two systems are highlighted in this perspective. In both cases, the presence of foreign surface species has been found to significantly alter the interactions of the metal oxides’ surfaces with oxygen. On the one hand, interactions are hindered due to the presence of certain impurities, such as the degradation of fuel cell cathode by Si‐species that originate from processing or from operating environments. On the other hand, electrochemically active noble metal additives have been intentionally used to tune the sensor response of metal oxides. In the case of electrochemically active additives, the need for operando spectroscopies to elucidate the mechanism is discussed. Electronic coupling of the surface additive with the metal oxide is found to play a central role in both cases. We use these results to demonstrate that insights gained from either field can be effectively applied to the other.

Surface-induced oxidation of Mn(II) and crystallization of manganese (hydr)oxides on clay minerals

The crystallization induced by foreign surfaces is crucial for various geological and geochemical processes on Earth’s surface, but the underlying mechanisms remain poorly understood. In this study, we investigated the oxidation of Mn(II) and crystallization of manganese (hydr)oxides (MnOx) on kaolinite (Kln) and montmorillonite (Mnt), two prevalent clay minerals in the nature with different structures and properties. Our results reveal that both Kln and Mnt surfaces can catalyze the heterogeneous oxidation of Mn(II) and crystallization of MnOx, but the crystallization pathways, as well as the morphologies and phases of the products, are distinct. The Mn(II) adsorbed by Kln’s outer surfaces were oxidized to Mn(III) and crystallized into MnOx, which were identified as hausmannite and manganite nanoaggregates. In contrast, the adsorption of Mn(II) and its oxidation to Mn(III) occurred both on the outer surfaces and interlayer spaces of Mnt, while the crystallization of MnOx only occurred on the outer surfaces, indicating that the confined volume of Mnt’s interlayer spaces can inhibit the crystallization of Mn(II/III) cations. Hausmannite emerged as the first MnOx product on Mnt, followed by groutite and manganite, all of which were well-dispersed fine nanoparticles. Additionally, the Si(IV) ions dissolved from Mnt participated in the formation of rhodonite with Mn(II), but this mineral phase was absent on Kln. Notably, MnOx nanoaggregates on Kln were assembled by a group of MnOx nanoparticles with slight misorientations among them, and the misorientations of these nanoparticles can gradually recover over time, indicating the contribution of crystallization by particle attachment (CPA). On the other hand, the strong electrostatic interactions between MnOx nanoparticles and Mnt surfaces reduced the mobility of nanoparticles, inhibiting their growth via CPA. Above results demonstrate the significant influence of the confinement effect and surface interactions on the surface-induced crystallization process of MnOx. These findings can also advance our knowledge about the role of clay minerals in Mn(II) oxidation and MnOx formation, and offer a possible explanation for the presence of various MnOx with diverse structures in the nature.

The role of acid–base interactions in the pitting corrosion of aluminum: a review

Abstract The review describes an electrode kinetic model of aluminum pitting nucleation taking into account the charge of the metal surface, the adsorption of chloride ions on the oxide surface, their penetration through the oxide film with the help of oxygen vacancies, and the dissolution of the underlying substrate with the initiation of pitting corrosion at the metal/oxide interface. It is shown that the critical pitting potential is a function of the potential of a thin layer of aluminum surface covered by oxide and the value of the pitting potential of a binary surface alloying is related to the isoelectric point of the alloying element oxide in the binary alloy. An electrode kinetic model of pitting initiation is described, which was used to explain the effect of surface alloying on the pitting initiation on binary alloys. A method for changing the surface charge by forming foreign surface organosilicon nanolayers bearing both negatively and positively charged groups was proposed. It has been established that four characteristics (q, Ψ 1-potential, E pit and the tendency of aluminum to depassivate) depend on the nature of ion-exchange groups, the degree of their acid dissociation, and the ion-chemical interaction with activator ions.

Microbial Biofilm: A Review on Formation, Infection, Antibiotic Resistance, Control Measures, and Innovative Treatment.

Biofilm is complex and consists of bacterial colonies that reside in an exopolysaccharide matrix that attaches to foreign surfaces in a living organism. Biofilm frequently leads to nosocomial, chronic infections in clinical settings. Since the bacteria in the biofilm have developed antibiotic resistance, using antibiotics alone to treat infections brought on by biofilm is ineffective. This review provides a succinct summary of the theories behind the composition of, formation of, and drug-resistant infections attributed to biofilm and cutting-edge curative approaches to counteract and treat biofilm. The high frequency of medical device-induced infections due to biofilm warrants the application of innovative technologies to manage the complexities presented by biofilm.

BIO18: Hemoglobin and Heme Scavenger Proteins Reduce Free Hemoglobin During Venovenous Extracorporeal Circulation and Preserves Microvascular Function.

Extracorporeal circulation procedures often utilize a blood pump to drive flow through an external circuit, which can cause hemolysis due to high shear conditions and foreign surface contact. The purpose of this study was to determine whether priming fluids containing proteins to sequester hemoglobin (Hb) and heme could be used in venovenous extracorporeal circulation (VV-ECC) to reduce their toxicity. A day prior to the experiment, male Golden Syrian hamsters were instrumented with a dorsal window chamber to monitor the microcirculation. The day of the experiment, both jugular veins were then cannulated under isoflurane anesthesia. Baseline (BL) microvascular oxygenation was measured using a hyperspectral camera. The animals were then heparinized (2.5 IU/g) and connected to the VV-ECC circuit, consisting of a peristaltic pump and bubble trap. The ECC circuit was primed with either 5% human serum albumin (HSA), ApoHb-Hp (62.01 mg/mL), or a protein solution containing hemopexin, transferrin, and Hp (protein cocktail, 84.50 mg/mL). Haptoglobin (Hp), hemopexin, and transferrin are native proteins that bind to Hb, heme, and iron respectively. Apohemoglobin (apoHb) is a synthetic scavenger produced by removing heme from Hb. ApoHb binds to haptoglobin (Hp) forming the apoHb-Hp complex that retains its ability to bind heme and scavenge free Hb. The experiment lasted a total of 2 hrs (Table 1), in which first the animals were hemodiluted, and the flow rate through the circuit was ramped up to 50% of the animal’s cardiac output. This max flow rate was then maintained for 35 minutes before being ramped down to 0.2 mLPM. The circuit was maintained at this flow rate for 15 minutes, allowing the animal and the circuit to equilibrate before the circuit flow was stopped. While mean arterial pressure (MAP, Figure 1a) showed differences at baseline (BL) between HSA and both other groups, there was no significance observed after hemodilution and the ramp up phase of the experiment. This difference in MAP between HSA and the two other solutions returned at all timepoints after the ramp up phase. Hb oxygen saturation (sO2, Figure 2) within the microvasculature showed a drop for both arterioles and venules in both the protein cocktail and ApoHb-Hp groups at the full VV-ECC timepoint. The plasma Hb (Figure 3) for the protein cocktail and ApoHb-Hp groups were significantly lower than the HSA control from the start of VV-ECC to the equilibration stage when compared to the HSA control. These results confirm that the ApoHb and protein cocktail solutions have the capability to bind and sequester free Hb, which has the potential to reduce the extravasation of Hb from the circulatory compartment into tissues, preserves the vascular nitric oxide (NO) signaling pathway, and reduce Hb and heme toxicity. Future work is needed to determine impact on organs, especially the kidneys, and to quantify the binding efficiency of these proteins to free hemoglobin.Figure 1. Hemodynamic parameters measured via the carotid artery: a) Mean arterial pressure (MAP) and b) heart rate (HR). bl = baseline, dil = hemodilution, up = ramp up, ecc = VV-ECC at max flow rate (50% of cardiac output), down = ramp down, equ = equilibration, off = off pump. * P < 0.05, ** P < 0.01, *** P < 0.001 between groups. N = 6 for all groups.Figure 2. Changes in microvascular hemoglobin oxygen saturation. The top row shows arterioles, while the bottom row shows venules. Arterioles and venules were analyzed for 4 hamsters per group. bl = baseline, dil = hemodilution, up = ramp up, ecc = VV-ECC at max flow rate (50% of cardiac output), down = ramp down, equ = equilibration, off = off pump. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 between groups. † P<0.05 compared to baseline (BL).Figure 3. a) Hematocrit (Hct) and b) plasma hemoglobin (pHb). 0 = baseline (BL), 25 = hemodilution, 45 = VV-ECC (start), 75 = VV-ECC (end), 105 = equilibrate, 120 = off pump. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 between groups. † P<0.05 compared to BL. Table 1. - Experimental timeline highlight the blood flow through the circuit. Baseline Hemodilution Ramp Up VV-ECC Ramp Down Equilibrate Off Pump Duration 15 min 15 min 15 min 35 min 15 min 15 min 10 min Blood Flow 0 mLPM 0.2 mLPM 0.2 mLPM → 50% CO 50% CO 50% CO → 0.2 mLPM 0.2 mLPM 0 mLPM Hyperspectral images were taken every 5 minutes. mLPM = milliliters per minute, CO = cardiac output, VV-ECC = full venovenous extracorporeal circulation.

Bivalirudin Superiority in Pediatric Berlin Hearts: Too Early to Draw Conclusions?

To the Editor: We commend Freniera et al. for their single-center retrospective review involving 31 pediatric Berlin Heart Ventricular Assist Devices anticoagulated with either bivaluridin or unfractionated heparin (UFH).1 We would like to highlight the need for robust performance assessment of the effects of these systematic anticoagulants, particularly during mechanical support. As a measure of inhibition of a single enzyme (activated coagulation factor X), the anti-factor-Xa (anti-Xa) assay represents a more direct measure of UFH activity than the activated partial thromboplastin time (aPTT), with reduced variability and minimal interference from biologic factors, such as lupus anticoagulants or elevated factor VIII.2 As such, the College of American Pathologists defines therapeutic reference ranges as direct measurements of heparin activity, such as anti-Xa. This is important, as divergent assay occurrence rates of up to 40%–60% may exist between groups whose systemic anticoagulant is titrated upon functionally different assays.3 The greater chest tube output and trend toward increased transfusion requirement in those receiving UFH may be explained by more intense anticoagulation while the rates of elevated D-dimer and plasma-free hemoglobin may be reflective of less vigorous anticoagulant effect. Corroborating this postulated causation, Freniere et al. found no differences in time to reach therapeutic aPTT between groups (5.7 vs. 12.6 hours, p = 0.149) despite profound variance when comparing bivalirudin titrated with aPTT and UFH managed with anti-Xa, which is derived from the markedly prolonged time to therapeutic range for UFH (69.5 hours).1 Accordingly, the concordance between aPTT and anti-Xa was found to be moderate (r = 0.63). Additionally, the impact of kidney impairment on bivalirudin pharmacokinetics needs to be accounted for. Although it remains impossible to determine the presence, nor the functional impact, of disparate anticoagulant intensities between groups with the data provided in this study, the lack of elucidation necessitates consideration before drawing definitive conclusions. Although we share the authors passion and enthusiasm for the administration of bivalirudin in the context of mechanical circulatory support due to the ease of dosing, the potential promise of enhanced outcomes,4 and favorable cost profile,5 caution must be urged before these advantages can be translated into the causation of yet to be determined superiority of clinical outcomes. We would also like to caution on the authors introduction of a term so-called VAD-itis seemingly on the basis of retrospective record entry or receipt of immunosuppressants. Although introducing foreign surfaces with mechanical devices triggers the inflammatory system, this “condition” should be identified via actions and judgment, not by any isolated immunological variable. For example, c-reactive protein was not different between groups.1 Considering that biofilm is formed, and the immune system evolves over time, an analysis of simple averages is of little value, even for the highly nonspecific c-reactive protein. While the authors discussion focused on methylprednisone, aspirin is also a potent immunomodulator whose dosing differed significantly between groups. However, to imply that higher aspirin dosing in bivalirudin group is related to more “VAD-it is” is an example of action taken as evidence, while not evidence or causation of any sort.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

Transient particle tracking microrheology of plasma coagulation via the intrinsic pathway

Abstract The maintenance of hemostasis to ensure vascular integrity is dependent upon the rapid conversion of zymogen species of the coagulation cascade to their enzymatically active forms. This process culminates in the generation of the serine protease thrombin and polymerization of fibrin to prevent vascular leak at sites of endothelial cell injury or loss of cellular junctions. Thrombin generation can be initiated by the extrinsic pathway of coagulation through exposure of blood to tissue factor at sites of vascular damage, or alternatively by the coagulation factor (F) XII activated by foreign surfaces with negative charges, such as glass, through the contact activation pathway. Here, we used transient particle tracking microrheology to investigate the mechanical properties of fibrin in response to thrombin generation downstream of both coagulation pathways. We found that the structural heterogeneity of fibrin formation was dependent on the reaction kinetics of thrombin generation. Pharmacological inhibition of FXII activity prolonged the time to form fibrin and increased the degree of heterogeneity of fibrin, resulting in fibrin clots with reduced mechanical properties. Taken together, this study demonstrates a dependency of the physical biology of fibrin formation on activation of the contact pathway of coagulation.