Time-Resolved Micro PIV in the Pivoting Area of the Triflo Mechanical Heart Valve

The Lapeyre-Triflo FURTIVA valve aims at combining the favorable hemodynamics of bioprosthetic heart valves with the durability of mechanical heart valves (MHVs). The pivoting region of MHVs is hemodynamically of special interest as it may be a region of high shear stresses, combined with areas of flow stagnation. Here, platelets can be activated and may form a thrombus which in the most severe case can compromise leaflet mobility. In this study we set up an experiment to replicate the pulsatile flow in the aortic root and to study the flow in the pivoting region under physiological hemodynamic conditions (CO = 4.5 L/min / CO = 3.0 L/min, f = 60 BPM). It was found that the flow velocity in the pivoting region could reach values close to that of the bulk flow during systole. At the onset of diastole the three valve leaflets closed in a very synchronous manner within an average closing time of 55 ms which is much slower than what has been measured for traditional bileaflet MHVs. Hot spots for elevated viscous shear stresses were found at the flanges of the housing and the tips of the leaflet ears. Systolic VSS was maximal during mid-systole and reached levels of up to 40 Pa

Leaflet Kinematics of Mechanical and Bioprosthetic Aortic Valve Prostheses.

The hemodynamic performance of artificial aortic valves (AVs) and the probability for structural valve deterioration can be linked to the valve kinematics. Comparability among different studies is limited because of variations in the experimental setups and physiologic boundary conditions. This study presents results of kinematic measurements of bioprosthetic and mechanical AVs that were tested in an identical experimental setting such that they can be directly compared with each other. The kinematics of AVs is typically presented in the form of the geometric orifice area and its temporal evolution. These parameters cannot capture asynchronous leaflet motion and out-of-plane leaflet velocity. In this work, each leaflet was tracked individually for a more detailed understanding of the leaflet kinematics, asynchronous leaflet motion, and leaflet tip velocities. A bioprosthetic valve, Edwards INTUITY (EINT), and two mechanical valves, Medtronic ADVANTAGE (MADV) and a Lapeyre-Triflo FURTIVA (TFUR), were tested in a compliant model of the aortic root in a physiologic flow loop. TFUR and MADV opened alike with maximum leaflet tip velocities of 0.77 and 0.66 m/s, respectively. The opening of EINT showed significantly higher local in-plane leaflet velocities of more than 2 m/s. EINT and TFUR exhibited similar early and slow closure. MADV closed significantly later with increased velocity. TFUR had a median maximum leaflet tip velocity of 0.39 m/s during valve closure and that of MADV was 0.83 m/s, whereas EINT exhibited a median maximum local in-plane leaflet velocity of 0.37 m/s. EINT experienced leaflet fluttering during systole with a flapping frequency of 36 Hz

Proteomic analysis of protein carbonylation: a useful tool to unravel nanoparticle toxicity mechanisms

Background: Oxidative stress, a commonly used paradigm to explain nanoparticle (NP)-induced toxicity, results from an imbalance between reactive oxygen species (ROS) generation and detoxification. As one consequence, protein carbonyl levels may become enhanced. Thus, the qualitative and quantitative description of protein carbonylation may be used to characterize how biological systems respond to oxidative stress induced by NPs. Methods: We investigated a representative panel of 24 NPs including functionalized amorphous silica (6), zirconium dioxide (4), silver (4), titanium dioxide (3), zinc oxide (2), multiwalled carbon nanotubes (3), barium sulfate and boehmite. Surface reactivities of all NPs were studied in a cell-free system by electron spin resonance (ESR). NRK-52E cells were treated with all NPs, analyzed for viability (WST-1 assay) and intracellular ROS production (DCFDA assay). Carbonylated proteins were assessed by 1D and/or 2D immunoblotting and identified by matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOF). In parallel, tissue homogenates from rat lungs intratracheally instilled with silver NPs were studied. Results: Eleven NPs induced elevated levels of carbonylated proteins. This was in good agreement with the surface reactivity of the NPs as obtained by ESR and the reduction in cell viability as assessed by WST-1 assay. By contrast, results obtained by DCFDA assay were deviating. Each NP induced an individual pattern of protein carbonyls on 2D immunoblots. Affected proteins comprised cytoskeletal components, proteins being involved in stress response, or cytoplasmic enzymes of central metabolic pathways such as glycolysis and gluconeogenesis. Furthermore, induction of carbonyls upon silver NP treatment was also verified in rat lung tissue homogenates. Conclusions: Analysis of protein carbonylation is a versatile and sensitive method to describe NP-induced oxidative stress and, therefore, can be used to identify NPs of concern. Furthermore, detailed information about compromised proteins may aid in classifying NPs according to their mode of action

Phosphonate coating of SiO2 nanoparticles abrogates inflammatory effects and local changes of the lipid composition in the rat lung: a complementary bioimaging study

Abstract Background The well-known inflammatory and fibrogenic changes of the lung upon crystalline silica are accompanied by early changes of the phospholipid composition (PLC) as detected in broncho-alveolar lavage fluid (BALF). Amorphous silica nanoparticles (NPs) evoke transient lung inflammation, but their effect on PLC is unknown. Here, we compared effects of unmodified and phosphonated amorphous silica NP and describe, for the first time, local changes of the PLC with innovative bioimaging tools. Methods Unmodified (SiO2-n), 3-(trihydroxysilyl) propyl methylphosphonate coated SiO2-n (SiO2-p) as well as a fluorescent surrogate of SiO2-n (SiO2-FITC) nanoparticles were used in this study. In vitro toxicity was tested with NR8383 alveolar macrophages. Rats were intratracheally instilled with SiO2-n, SiO2-p, or SiO2-FITC, and effects on lungs were analyzed after 3 days. BALF from the right lung was analyzed for inflammatory markers. Cryo-sections of the left lung were subjected to fluorescence microscopy and PLC analyses by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MS), Fourier transform infrared microspectroscopy (FT-IR), and tandem mass spectrometry (MS/MS) experiments. Results Compared to SiO2-p, SiO2-n NPs were more cytotoxic to macrophages in vitro and more inflammatory in the rat lung, as reflected by increased concentration of neutrophils and protein in BALF. Fluorescence microscopy revealed a typical patchy distribution of SiO2-FITC located within the lung parenchyma and alveolar macrophages. Superimposable to this particle distribution, SiO2-FITC elicited local increases of phosphatidylglycerol (PG) and phosphatidylinositol (PI), whereas phoshatidylserine (PS) and signals from triacylgyceride (TAG) were decreased in the same areas. No such changes were found in lungs treated with SiO2-p or particle-free instillation fluid. Conclusions Phosphonate coating mitigates effects of silica NP in the lung and abolishes their locally induced changes in PLC pattern. Bioimaging methods based on MALDI-MS may become a useful tool to investigate the mode of action of NPs in tissues

Additional file 1: of Phosphonate coating of SiO2 nanoparticles abrogates inflammatory effects and local changes of the lipid composition in the rat lung: a complementary bioimaging study

Figure S1. Effect of different SiO2 NP on lung histology. Figure S2. MALDI-MS/MS spectrum resulting from the fragmentation of precursor m/z 721.4. Figure S3. MALDI-MS/MS spectrum resulting from the fragmentation of precursor m/z 861.5. Figure S4. Ion images from a vehicle-treated control lung. Figure S5. Ion images from a SiO2-p-treated control lung. (DOCX 1889 kb

Additional file 1: Figure S1-S5 of Proteomic analysis of protein carbonylation: a useful tool to unravel nanoparticle toxicity mechanisms

and Table S1. The file contains various additional figures and tables, collected in a single portable documend file (PDF) (DOC 9935 kb)