The optimal incubation time for in vitro hemocompatibility testing:Assessment using polymer reference materials under pulsatile flow with physiological wall shear stress conditions

During hemocompatibility testing, activation products may reach plateau values which can result in less distinction between hemocompatible and hemo-incompatible materials. Of concern is an underestimation of the blood activation caused by the biomaterial of interest, which may result in a false assessment of hemocompatibility. To elucidate the optimal incubation time for in vitro hemocompatibility testing, we used the Haemobile circulation model with human whole blood. Blood from healthy volunteers was in vitro incubated under pulsatile flow with physiological wall shear stress conditions at 37 degrees C for 30, 60, 120, or 240 min. Test loops containing low-density polyethylene and polydimethylsiloxane served as low and high reference materials, that is, hemocompatible and hemo-incompatible biomaterials, respectively. In addition, empty loops served as a negative reference. Thrombogenicity, platelet function, inflammatory response, coagulation, and hemolysis between references and incubation times were compared. We found that thrombogenicity and platelet function were significantly affected by both the duration of incubation and the type of material. In particular, thrombogenicity and platelet function assessments were affected by incubation time. We found that an exposure time of 60 min was sufficient, and for almost all variables an optimal incubation time to discriminate between the low and high reference material. (c) 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2335-2342, 2019

Skin- and Plasmaautofluorescence in hemodialysis with glucose-free or glucose-containing dialysate

Abstract Background Haemodialysis (HD) patients suffer from an increased risk of cardiovascular disease (CVD). Skin autofluorescence (SAF) is a strong marker for CVD. SAF indirectly measures tissue advanced glycation end products (AGE) being cumulative metabolites of oxidative stress and cytokine-driven inflammatory reactions. The dialysates often contain glucose. Methods Autofluorescence of skin and plasma (PAF) were measured in patients on HD during standard treatment (ST) with a glucose-containing dialysate ( n \u2009=\u200924). After that the patients were switched to a glucose-free dialysate (GFD) for a 2-week period. New measurements were performed on PAF and SAF after 1\ua0week (M1) and 2\ua0weeks (M2) using GFD. Nonparametric paired statistical analyses were performed between each two periods. Results SAF after HD increased non-significantly by 1.2% while when a GFD was used during HD at M1, a decrease of SAF by 5.2% ( p \u2009=\u20090.002) was found. One week later (M2) the reduction of 1.6% after the HD was not significant ( p \u2009=\u20090.33). PAF was significantly reduced during all HD sessions. Free and protein-bound PAF decreased similarly whether glucose containing or GFD was used. The HD resulted in a reduction of the total PAF of approximately 15%, the free compound of 20% and the protein bound of 10%. The protein bound part of PAF corresponded to approximately 56% of the total reduction. The protein bound concentrations after each HD showed the lowest value after 2\ua0weeks using glucose-free dialysate ( p \u2009<\u20090.05). The change in SAF could not be related to a change in PAF. Conclusions When changing to a GFD, SAF was reduced by HD indicating that such measure may hamper the accumulation and progression of deposits of AGEs to protein in tissue, and thereby also the development of CVD. Glucose-free dialysate needs further attention. Protein binding seems firm but not irreversible. Trial registration ISRCTN registry: ISRCTN13837553 . Registered 16/11/2016 (retrospectively registered)

In vitro blood flow model with physiological wall shear stress for hemocompatibility testing-An example of coronary stent testing

Hemocompatibility of blood contacting medical devices has to be evaluated before their intended application. To assess hemocompatibility, blood flow models are often used and can either consist of in vivo animal models or in vitro blood flow models. Given the disadvantages of animal models, in vitro blood flow models are an attractive alternative. The in vitro blood flow models available nowadays mostly focus on generating continuous flow instead of generating a pulsatile flow with certain wall shear stress, which has shown to be more relevant in maintaining hemostasis. To address this issue, the authors introduce a blood flow model that is able to generate a pulsatile flow and wall shear stress resembling the physiological situation, which the authors have coined the "Haemobile." The authors have validated the model by performing Doppler flow measurements to calculate velocity profiles and ( wall) shear stress profiles. As an example, the authors evaluated the thrombogenicity of two drug eluting stents, one that was already on the market and one that was still under development. After identifying proper conditions resembling the wall shear stress in coronary arteries, the authors compared the stents with each other and often used reference materials. These experiments resulted in high contrast between hemocompatible and incompatible materials, showing the exceptional testing capabilities of the Haemobile. In conclusion, the authors have developed an in vitro blood flow model which is capable of mimicking physiological conditions of blood flow as close as possible. The model is convenient in use and is able to clearly discriminate between hemocompatible and incompatible materials, making it suitable for evaluating the hemocompatible properties of medical devices. (C) 2016 Author(s)

Biomarkers of Lung Injury in Cardiothoracic Surgery

Diagnosis of pulmonary dysfunction is currently almost entirely based on a vast series of physiological changes, but comprehensive research is focused on determining biomarkers for early diagnosis of pulmonary dysfunction. Here we discuss the use of biomarkers of lung injury in cardiothoracic surgery and their ability to detect subtle pulmonary dysfunction in the perioperative period. Degranulation products of neutrophils are often used as biomarker since they have detrimental effects on the pulmonary tissue by themselves. However, these substances are not lung specific. Lung epithelium specific proteins offer more specificity and slowly find their way into clinical studies

In vitro hemocompatibility testing: The importance of fresh blood

The use of unactivated blood for hemocompatibility testing is essential to obtain reliable results. Here, the authors study the influence of heparinized whole blood storage time and temperature on blood activation and evaluate the importance of initiating hemocompatibility tests within 4 h of blood collection. Blood from healthy volunteers was collected and analyzed with minimal delay, after 30 min and after 60 min of storage at room temperature, 30 or 37 degrees C. In addition, blood was analyzed after 1, 2, or 4 h of storage at room temperature. Platelet count, mean platelet volume, platelet binding capacity to collagen and thromboxane B2 were measured to assess platelet function, complement complex C5b-9 and elastase were measured to assess activation of the inflammatory response system, and thrombin-antithrombin III was measured to assess activation of the coagulation system. Furthermore, free hemoglobin was measured in platelet poor plasma as an indicator for red blood cell damage. The authors found that storage at 30 degrees C significantly increased platelet and coagulation activity after 60 min and storage at 37 degrees C significantly increased platelet, coagulation, and white blood cell activity after 60 min. Storage at room temperature significantly decreased platelet binding to collagen after 4 h and increased platelet activity after 1 h onward and white blood cell activity after 4 h. Their results show that short-term storage of heparinized whole blood significantly influences biomarkers over time, especially at 30 and 37 degrees C compared to room temperature. However, blood stored at room temperature for 4 h is also affected. In particular, platelet function and white blood cell activity are significantly influenced after 4 h of stationary storage at room temperature; therefore, the authors propose that hemocompatibility tests should be initiated well within 4 h of blood collection, preferably within 2 h. (C) 2016 Author(s)

Incidence of Massive Transfusion and Overall Transfusion Requirements During Lung Transplantation Over a 25-Year Period

Objective: To establish the incidence of massive transfusion and overall transfusion requirements during lung transplantation, changes over time, and association with outcome in relation to patient complexity. Design: Retrospective cohort study. Setting: University hospital. Participants: All 514 adult patients who underwent transplantation from 1990 until 2015. Interventions: None. Measurements and Main Results: Patient records and transfusion data, divided into 5-year intervals, were analyzed. The incidence of massive transfusion (>10 units of red blood cells [RBCs] in 24 h) was 27% and did not change over time, whereas the median (interquartile range) transfusion requirement in the whole cohort decreased from 8 (5-12) to 3 (0-10) RBCs (p <0.001). In patients transplanted from the intensive care unit, the incidence of massive transfusion increased over time from 25% to 54% (p = 0.04) and median transfusion requirements from 4.5 (3-8.5) units to 14.5 (5-26) units of RBCs (p = 0.03). Multivariable analysis showed that circulatory support, pulmonary hypertension, re-transplantation, cystic fibrosis, Eisenmenger syndrome, bilateral transplantation, and low body mass index were associated with massive transfusion. Patients with massive transfusion had more primary graft dysfunction grade III at 0, 24, 48, and 72 hours (p <0.001), higher 30-day mortality (13% v 4%; p <0.001), and lower 5-year survival (hazard ratio 3.67 [95% confidence interval 1.72-7.85]; p <0.001). Conclusion: The incidence of massive transfusion did not change over time, whereas transfusion requirements in the whole cohort decreased. In patients transplanted from the intensive care unit, massive transfusion and transfusion requirements increased. Massive transfusion was associated with poor outcome. (C) 2019 Elsevier Inc. All rights reserved