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Biomedical subjects

G B Fiore

Publications and source records attributed to G B Fiore.

17 recordsLinked to original sources
PubMed2006

Multi-scale analysis of the toraymyxin adsorption cartridge. Part I: molecular interaction of polymyxin B with endotoxins.

Endotoxins or lipopolysaccharides are the main constituents of the outer leaflet of Gram-negative bacteria membrane and play a central role in the pathogenesis of the septic shock. Polymyxin B has both antibacterial and antiendotoxin capability; indeed it is able to destroy the bacterial outer membrane and bind endotoxin neutralizing its toxic effects. Cartridges containing polymyxin B-immobilized fibers (Toraymyxin PMX-F, Toray Industries, Japan) are used in extracorporeal hemoperfusion to remove circulating endotoxin. The aim of this study is the characterization of the polymyxin B-endotoxin system at the molecular level, thus providing quantitative evaluation of the binding forces exerted in the molecular complex. Polymyxin B was interfaced with five molecular models of lipopolysaccharides differing in their structure and molecular mechanics simulations were performed at different intermolecular distances aimed at calculating the interaction energies of the complex. Binding forces were calculated by fitting interaction energies data. Results show that in the short range the polymyxin B-endotoxin complex is mediated by hydrophobic forces and in the long range the complex is driven by ionic forces only. From a mechanical standpoint, polymyxin B-endotoxin complex is characterized by maximum binding forces ranging between 1.39 nN to 3.79 nN. The knowledge of the binding force behavior at different intermolecular distances allows further investigations at higher scale level (Part II).

Anti-Bacterial Agents↗
PubMed2005

A mechanical model lung for hydraulic testing of total liquid ventilation circuits.

A new model lung (ML), designed to reproduce the tracheal pressure vs. fluid flow relationship in animals undergoing total liquid ventilation (TLV) trials, was developed to be used as a mock bench test for neonatal TLV circuits. The ML is based on a linear inertance-resistance-compliance (LRC) lumped-parameter model of the respiratory system with different resistance values for inspiration (R insp ) or expiration (R exp ). The resistant element was set up using polypropylene hollow fibres packed inside a tube. A passive one-way valve was used to control the resistance cross-section area provided for the liquid to generate different values for R insp or R exp , each adjustable by regulating the active length of the respective fibre pack. The compliant element consists of a cylindrical column reservoir, in which bars of different diameter were inserted to adjust compliance (C). The inertial phenomena occurring in the central airways during TLV were reproduced by specifically dimensioned conduits into which the endotracheal tube connecting the TLV circuit to the ML was inserted. A number of elements with different inertances (L) were used to simulate different sized airways. A linear pressure drop-to-flow rate relationship was obtained for flow rates up to 5 l/min. The measured C (0.8 to 1.3 mL cmH2O (-1) kg(-1)), R insp (90 to 850 cmH2O s l(-1)), and R exp (50 to 400 cmH2O s l(-1)) were in agreement with the literature concerning animals weighing from 1 to 12 kg. Moreover, features observed in data acquired during in vivo TLV sessions, such as pressure oscillations due to fluid inertia in the upper airways, were similarly obtained in vitro thanks to the inertial element in the ML.

Animals↗
PubMed2004

A numerical and experimental study of compliance and collapsibility of preterm lamb tracheae.

Knowledge of the mechanical behaviour of immature tracheae is crucial in order to understand the effects exerted on central airways by ventilatory treatments, particularly of Total Liquid Ventilation. In this study, a combined experimental and computational approach was adopted to investigate the compliance and particularly collapsibility of preterm lamb tracheae in the range of pressure likely applied during Total Liquid Ventilation (-30 to 30 cmH2O). Tracheal samples of preterm lambs (n = 5; gestational age 120-130 days) were tested by altering transmural pressure from -30 to 30 cmH2O. Inflation (Si) and collapsing (Sc) compliance values were calculated in the ranges 0 to 10 cmH2O and -10 to 0 cmH2O, respectively. During the tests, an asymmetric behaviour of the DeltaV/V0 vs. P curves at positive and negative pressure was observed, with mean Si = 0.013 cmH2O(-1) and Sc = 0.053 cmH2O(-1). A different deformed configuration of the sample regions was observed, depending on the posterior shape of cartilaginous ring. A three-dimensional finite-element structural model of a single tracheal ring, based on histology measurements of the tested samples was developed. The model was parameterised in order to represent rings belonging to three different tracheal regions (craniad, median, caudal) and numerical analyses replicating the collapse test conditions were performed to evaluate the ring collapsibility at pressures between 0 and -30 cmH2O. Simulation results were compared to experimental data to verify the model's reliability. The best model predictions occurred at pressures -30 to -10 cmH2O. In this range, a model composed of median rings best interpreted the experimental data, with a maximum error of 2.7%; a model composed of an equal combination of all rings yielded an error of 12.6%.

Animals↗
PubMed2004

Clinical evaluation of internal hemodiafiltration (iHDF): a diffusive-convective technique performed with internal filtration enhanced high-flux dialyzers.

AIM: Efficiency in removing middle molecules such as beta2-microglobulin (beta2-MG) is one of the main purposes of modern dialytic therapy. In order to achieve this, techniques requiring complex machines and substitution fluid have been developed over recent years. Alternatively, the internal filtration/back filtration phenomenon can be used. The recent development of a so-called "internal filtration enhanced dialyser" prompted us to compare the removal of beta2-MG together with other small molecules when the dialyser was used either in standard hemodiafiltration (HDF) or internal hemodiafiltration (iHDF). METHODS: Ten stable, anuric, hemodialysis (HD) patients treated by thrice weekly standard bicarbonate HD using low-flux synthetic membrane entered the study. A new high-flux polysulfone dialyser designed with the specific aim of enhancing internal filtration (BS-1.6 UL, 1.6 m2, Toray Industries) was used. Post dilution HDF (2.5 l/hour of substitution fluid, dialysate flow 500 ml/min) was compared with iHDF (dialysate flow 750 ml/min), with blood flow at 300 ml/min. Samples were obtained at the start and at the end of the session in order to measure the % removal of urea, creatinine, uric acid, phosphate and beta2-MG (corrected for total protein concentration). In addition, after 20 min of dialysis the clearances of the same molecules were measured. A mathematical model has been developed for the description of the hydrodynamic phenomena taking place within the dialyser and of fluid filtration across the membrane. RESULTS: No significant differences have been observed in removal rate switching from HDF to iHDF except for beta2-MG removal, which was slightly higher in HDF than in iHDF Phosphate clearance is significantly higher than those obtained with creatinine in both HDF (p<0.005) and iHDF (p<0.01) modalities. The total convection calculated with the model is reduced with respect to HDF only by 24% (4100 ml/h vs. 5400 ml/h on the average). CONCLUSIONS: iHDF is a high flux dialysis method, which, if performed with a dialyser designed to enhance internal filtration, obtains a much higher removal rate in comparison with dialysers in traditional high flux dialysis, as previously reported in the literature. Provided that the dialyser is used on a dialysis machine working with ultra pure dialysate and UF control, this dialyser line can perform reliable internal HDF without the need for replacement solution. Considering the narrow difference in performance observed between iHDF and HDF, and the increasing number (and age) of patients leading to higher dialysis costs, iHDF represents a cost-effective alternative to other diffusive-convective techniques.

Aged↗
PubMed2003

Perfluorocarbons attenuate oxidative lung damage.

The aim of this study was to investigate the effect of tidal liquid ventilation (TLV) compared to conventional mechanical ventilation (CMV) on oxidative lung damage in the setting of acute respiratory distress syndrome (ARDS). After repeated lung lavages, 10 minipigs were treated with CMV or TLV for 4 hr before the animals were sacrificed. Samples for blood gas analysis and bronchial aspirate samples were withdrawn before the induction of lung injury, and at 10 min, 2 hr, and 4 hr after the beginning of ventilatory support. To assess lung oxidative damage, total hydroperoxide (TH) and advanced oxidation protein product (AOPP) concentrations were measured in bronchial aspirate samples. After 2 and 4 hr of ventilatory support, partial oxygen tension (PaO(2)) and base excess (BE) were significantly higher in the TLV group than in the CMV group, while PaCO(2) was slightly higher, but with no statistical significance. In the CMV group, the AOPP level was significantly higher at 4 hr than at baseline. TH and AOPP bronchial aspirate concentrations were higher in the CMV group than in the TLV group at 2 and 4 hr of ventilation. We conclude that animals treated with TLV showed lower oxidative lung damage compared to animals treated with CMV.

Animals↗
PubMed2002

Mechanobiology of engineered cartilage cultured under a quantified fluid-dynamic environment.

Natural cartilage remodels both in vivo and in vitro in response to mechanical forces and hence mechanical stimulation is believed to have a potential as a tool to modulate extra-cellular matrix synthesis in tissue-engineered cartilage. Fluid-induced shear is known to enhance chondrogenesis on animal cells. A well-defined hydrodynamic environment is required to study the biochemical response to shear of three-dimensional engineered cell systems. We have developed a perfused-column bioreactor in which the culture medium flows through chondrocyte-seeded porous scaffolds, together with a computational fluid-dynamic model of the flow through the constructs' microstructure. A preliminary experiment of human chondrocyte growth under static versus dynamic conditions is described. The median shear stress imposed on the cells in the bioreactor culture, as predicted by the CFD model, is 3 x 10(-3) Pa (0.03 dyn/cm(2)) at a flow rate of 0.5 ml/min corresponding to an inlet fluid velocity of 44.2 mum/s. Providing a fluid-dynamic environment to the cells yielded significant differences in cell morphology and in construct structure.

Bioreactors↗
PubMed2002

Hydraulic functional characterisation of aortic mechanical heart valve prostheses through lumped-parameter modelling.

Lumped-parameter modelling techniques are proposed as a method for studying the hydraulic characteristics of mechanical prosthetic heart valves (PHVs). The global hydraulic behaviour of PHVs in the open position was modelled by taking into account the (nonlinear) resistive and (linear) inertial factors governing the time-dependent relationship between transvalvular pressure drop and fluid flow rate, and neglecting the leaflets' opening and closure transient phenomena. Statistically defined indices associated to the parameters' values attest how properly the model describes PHV hydraulic behaviour. Local fluid dynamics is not modelled with this approach. The proposed method was implemented in a software program and applied to the characterisation of the aortic StJude Medical, StJude Medical Hemodynamic Plus and CarboMedics PHVs, basing on steady- and pulsatile-flow hydraulic-bench experimental data. The results showed that reliable parameters expressing hydraulic resistance can be derived from steady-flow data (R(2)>0.995). Inertance parameters derived from pulsatile-flow experiments are liable to a degree of uncertainty (confidence intervals up to 17%), however, comparing the reconstructed vs. measured pressure drop during systolic time demonstrates that this deficiency is mostly due to the missing description of initial, transient oscillations presumably related to the leaflets' opening (not modelled).

Aortic Valve↗
PubMed2001

In vitro steady-flow analysis of systemic-to-pulmonary shunt haemodynamics.

A modified Blalock-Taussig shunt is a connection created between the systemic and pulmonary arterial circulations to improve pulmonary perfusion in children with congenital heart diseases. Survival of these patients is critically dependent on blood flow distribution between the pulmonary and systemic circulations which in turn depends upon the flow resistance of the shunt. Previously, we investigated the pressure-flow relationship in rigid shunts with a computational approach. to estimate the pulmonary blood flow rate on the basis of the in vivo measured pressure drop. The present study aims at evaluating, in vitro how the anastomotic distensibility and restrictions due to suture presence affect the shunt pressure-flow relationship. Two actual Gore-Tex shunts (3 and 4 mm diameters) were sutured to compliant conduits by a surgeon and tested at different steady flow rates (0.25-11 min(-1)) and pulmonary pressures (3-34 mmHg). Corresponding computational models were also created to investigate the role of the anastomotic restrictions due to sutures. In vitro experiments showed that pulmonary artery pressure affects the pressure-flow relationship of the anastomoses. particularly at the distal site. However, this occurrence scarcely influences the total shunt pressure drop. Comparisons between in vitro and computational models without anastomotic restrictions show that the latter underestimates the in vitro pressure drops at any flow rate. The addition of the anastomotic restrictions (31 and 47% of the original area of 3 and 4 mm shunts, respectively) to the computational models reduces the gap, especially at high shunt flow rate and high pulmonary pressure.

Anastomosis, Surgical↗
PubMed2001

A model of neonatal tidal liquid ventilation mechanics.

Tidal liquid ventilation (TLV) with perfluorocarbons (PFC) has been proposed to treat surfactant-deficient lungs of preterm neonates, since it may prevent pulmonary instability by abating saccular surface tension. With a previous model describing gas exchange, we showed that ventilator settings are crucial for CO(2) scavenging during neonatal TLV. The present work is focused on some mechanical aspects of neonatal TLV that were hardly studied, i.e. the distribution of mechanical loads in the lungs, which is expected to differ substantially from gas ventilation. A new computational model is presented, describing pulmonary PFC hydrodynamics, where viscous losses, kinetic energy changes and lung compliance are accounted for. The model was implemented in a software package (LVMech) aimed at calculating pressures (and approximately estimate shear stresses) within the bronchial tree at different ventilator regimes. Simulations were run taking the previous model's outcomes into account. Results show that the pressure decrease due to high saccular compliance may compensate for the increased pressure drops due to PFC viscosity, and keep airway pressure low. Saccules are exposed to pressures remarkably different from those at the airway opening; during expiration negative pressures, which may cause airway collapse, are moderate and appear in the upper airways only. Delivering the fluid with a slightly smoothed square flow wave is convenient with respect to a sine wave. The use of LVMech allows to familiarize with LV treatment management taking the lungs' mechanical load into account, consistently with a proper respiratory support.

Carbon Dioxide↗
PubMed2000

The pumping oxygenator: design criteria and first in vitro results.

A new project is presented, the pumping oxygenator, functionally integrating pulsatile pumping and blood oxygenation in a single device. Solid, semipermeable silicone membranes allow gas exchange and simultaneously transfer energy from pressurized gas to blood thanks to their distensibility and to inlet and outlet 1-way valves. Two small-sized (1 m2 exchange surface area) prototypes were designed, constructed, hydraulically characterized, and subjected to gas transfer evaluation tests. Blood flow rates (Q(b)) up to 1,250 ml/min were obtained with 30 mm Hg static preload and 130 mm Hg afterload with 0.7 m upstream and 2.1 m downstream 3/8 inch pipes. Physiological oxygen transfer (VO2 = 5 ml/dl, ml of transferred O2/dl of treated blood) was delivered at Q(b) < 900 ml/min, about 4 ml/dl at Q(b) = 1,250 ml/min. VO2 also was significantly increased by increasing percent systolic time. CO2 transfer decreased regularly with increasing Q(b) from VCO2 = 4.8 ml/dl at Q(b) = 400 ml/min to VCO 2 = 2.1 ml/dl at Q(b) = 1,250 ml/min. The results confirm the possibility of integrating oxygenation and pulsatile pumping. The pumping oxygenator represents a promising project deserving further improvements.

Blood Flow Velocity↗
PubMed1998

Mass transfer efficiency of a commercial hollow fibre oxygenator during six-hour in vitro perfusion with steady and with pulsatile blood flow.

Detailed data about the behaviour of commercial membrane oxygenators with pulsatile blood flow are rarely available. This work deals with an experimental evaluation of the effects induced on gas transfer efficiency by pulsatile perfusion of a hollow fibre oxygenator (Monolyth Sorin Biomedica). The oxygenator was subjected to two in vitro trials both carried out with identical experimental protocols except for the flow type, steady and pulsatile. A roller pump with pulsatile module (Stöckert Instrument) was used to generate both flow types. Three different mean blood flow rates (3.2, 4.0 and 4.8 L/min) were tested. The experiments lasting six hours were carried out using bovine blood with inlet conditions according to AAMI standard requirements. Blood samples were withdrawn every hour and the calculated gas transfer obtained in the two sessions were compared. The device proved to be well-designed for steady flow and to be liable to similar gas transfer performance when used in pulsatile conditions. Furthermore, the use of pulsatile flow rather than steady flow provided more consistent conditions and resulted in a higher eventual oxygen transfer efficiency (final mean difference = 6.2%, p < 0.05), proving to be able to avoid any performance decays.

Animals↗
PubMed1998

Effects of blood flow pulse frequency on mass transfer efficiency of a commercial hollow fibre oxygenator.

The clinical advantages achievable through pulsatile blood perfusion during cardio-pulmonary bypass have recently suggested the design of new pulsatile systems for extracorporeal circulation. Still it is not clear whether current commercial membrane oxygenators could be adopted with such systems, since their behaviour with pulsatile perfusion has not been satisfactorily documented yet. In a previous paper, we assessed that pulsatile perfusion of a widely used hollow fibre oxygenator (Sorin Monolyth) at 60 bpm provides more time-consistent oxygen transfer than steady perfusion. The present work is aimed to evaluate how the pulse frequency influences the gas transfer performance of the same device. The oxygenator was subjected to in vitro trials using a roller pump with pulsatile module (Stockert Instrumente) to generate pulsed flow. Four different pulse frequencies (45, 60, 75 and 90 bpm) were investigated at a fixed blood flow rate (4.0 l/min). The experiments lasting six hours were carried out using bovine blood with inlet conditions according to AAMI standards requirements. Blood samples were withdrawn every hour and O2 and CO2 transfer rates were evaluated. The experimental findings confirm that with pulsatile blood flow no time decay take place during prolonged perfusion. Moreover, when pulse frequency increases, transition levels occur for both O2 and CO2. Over these thresholds gas transfer rates display significant increases (p < 0.05), though of little magnitude (up to 2.5% for oxygen over 60 bpm; up to 3.7% for carbon dioxide over 75 bpm).

Animals↗
PubMed1997

Liquid ventilation: a mathematical model of gas diffusion in the premature lung.

The liquid ventilation (LV) technique was previously demonstrated to be a valuable alternative to ordinary gas ventilation, particularly for newborn patients with severely distressed lungs. This work describes a mathematical model of gas transfer phenomena occurring within the lungs of a preterm newborn baby ventilated with liquid perfluorocarbon (PFC) RM-101. The model was conceived in order to perform computer simulations of LV treatments. Its input parameters are tidal volume, respiratory frequency, oxygen and carbon dioxide tension in inlet PFC; its output data are the partial pressures of respiratory gases in the alveolar environment. Such values may be evaluated at any instant from the beginning of the treatment, in order to judge whether the therapy is able to meet the necessary conditions to arterialize properly the patient's venous blood. The model also enables optimisation procedures to be defined and performed. Quantitative results and graphs are supplied, with reference to the simulation of LV applied to a preterm newborn of 28 gestational weeks. The main results point out that a relatively short duration of initial transients is attainable (200 to 240 s) and that blood arterialization is possible even with low oxygen tension in inlet PFC (29.7 kPa (223 mmHg)).

Biomedical Engineering↗
PubMed1996

Normalization of experimental results with respect to inlet conditions in membrane oxygenator testing.

This study looked at the problem of the excessive variability in oxygenator testing results, induced by variation of inlet parameters, particularly of inlet oxyhaemoglobin saturation. The investigation was carried out in the laboratory. An in vitro circuit was used to perfuse a small oxygenating cell. Blood flow rate (BFR) and film thickness (BFT) were varied to obtain different oxygenation conditions, while the inspired oxygen fraction (FiO2) and ventilation ratio were kept at constant values. With each test condition, inlet saturation was varied in the range 60-70% and a number of veno-arterial blood samples (at least 20) were withdrawn and analysed for numerical computing and statistical analysis. The generic law relating oxygenation increment to inlet saturation was found. This allowed a useful normalization procedure to be applied to oxygenator testing results and render them comparable, even if obtained at different inlet conditions.

Humans↗
PubMed1984

High-performance liquid chromatographic separation and quantification of alanopine and strombine in crude tissue extracts.

A method for the separation and quantification of the levels of alanopine and strombine in neutralized, perchloric acid extracts of tissues of marine invertebrates is presented. The method is based on high-performance liquid chromatographic (HPLC) separation, postcolumn derivatization using o-phthaldialdehyde and sodium hypochlorite, and subsequent fluorometric detection. Isocratic separation results in the rapid elution of alanopine and strombine, with elution times of 4.7 and 5.4 min, respectively. The sensitivity of this method is in the range 50-250 pmol. However, the fluorometric detection approach provides the capability for even greater sensitivity.

Alanine↗