Inhibition of Thrombin in Cardiac Surgery : experiments in a porcine model

Cardiac surgery involving cardiopulmonary bypass (CPB) induces activation of inflammation and coagulation systems and is associated with ischemia-reperfusion injury (I/R injury)in various organs including the myocardium, lungs, and intestine. I/R injury is manifested as organ dysfunction. Thrombin, the key enzyme of coagulation , plays a cenral role also in inflammation and contributes to regulation of apoptosis as well. The general aim of this thesis was to evaluate the potential of thrombin inhibition in reducing the adverse effects of I/R injury in myocardium, lungs, and intestine associated with the use of CPB and cardiac surgery. Forty five pigs were used for the studies. Two randomized blinded studies were performed. Animals underwent 75 min of normothermic CPB, 60 min of aortic clamping, and 120 min of reperfusion period. Twenty animals received iv. recombinant hirudin, a selective and effective inbitor of thrombin, or placebo. In a similar setting, twenty animals received an iv-bolus (250 IU/kg) of antithrombin (AT) or placebo. An additional group of 5 animals received 500 IU/kg in an open label setting to test dose response. Generation of thrombin (TAT), coagulation status (ACT), and hemodynamics were measured. Intramucosal pH and pCO2 were measured from the luminal surface of ileum using tonometry simultaneusly with arterial gas analysis. In addition, myocardial, lung, and intestinal biopsies were taken to quantitate leukocyte infiltration (MPO), for histological evaluation, and detection of apoptosis (TUNEL, caspase 3). In conclusion, our data suggest that r-hirudin may be an effective inhibitor of reperfusion induced thrombin generation in addition to being a direct inhibitor of preformed thrombin. Overall, the results suggest that inhibition of thrombin, beyond what is needed for efficient anticoagulation by heparin, has beneficial effects on myocardial I/R injury and hemodynamics during cardiac surgery and CPB. We showed that infusion of the thrombin inhibitor r-hirudin during reperfusion was associated with attenuated post ischemia left ventricular dysfunction and decreased systemic vascular resistance. Consequently microvascular flow was improved during ischemia-reperfusion injury. Improved recovery of myocardium during the post-ischemic reperfusion period was associated with significantly less cardiomyocyte apoptosis and with a trend in anti-inflammatory effects. Thus, inhibition of reperfusion induced thrombin may offer beneficial effects by mechanisms other than direct anticoagulant effects. AT, in doses with a significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of myocardial recovery, histological inflammatory changes or post-ischemic troponin T release. Instead, AT attenuated reperfusion induced increase in pulmonary pressure after CPB. Taken the clinical significance of postoperative pulmonary hemodynamics in patients undergoing cardiopulmonary bypass, the potential positive regulatory role of AT and clinical implications needs to be studied further. Inflammatory response in the gut wall proved to be poorly associated with perturbed mucosal perfusion and the animals with the least neutrophil tissue sequestration and I/R related histological alterations tended to have the most progressive mucosal hypoperfusion. Thus, mechanisms of low-flow reperfusion injury during CPB can differ from the mechanisms seen in total ischemia reperfusion injury.

Multiphase porous media model for Intermittent Microwave Convective Drying (IMCD) of food

Intermittent microwave convective (IMCD) drying is an advanced drying technology that improves both energy efficiency and food quality during the drying of food materials. Despite numerous experimental studies available for IMCD, there is no complete multiphase porous media model available to describe the process. A multiphase porous media model considering liquid water, gases and the solid matrix inside the food during drying can provide in depth understanding of IMCD. In this article, firstly a multiphase porous media model was developed for IMCD. Then the model is validated against experimental data by comparing moisture content and temperature distributions after each heating and tempering periods. The profile of vapour pressures and evaporation during IMCD are presented and discussed. The relative contribution of water and vapour fluxes due to gas pressure and diffusion demonstrated that the fluxes due are relatively higher in IMCD compared to convection drying and this makes the IMCD faster.

Temperature- and pressure-dependent study of Cl-35 NQR frequency and spin lattice relaxation time in 2,3-dichloroanisole

The temperature and pressure dependence of Cl-35 NQR frequency and spin lattice relaxation time (T-1) were investigated in 2,3-dichloroanisole. Two NQR signals were observed throughout the temperature and pressure range studied. T-1 were measured in the temperature range from 77 to 300 K and from atmospheric pressure to 5 kbar. Relaxation was found to be due to the torsional motion of the molecule and also reorientation f motion of the CH3 group. T-1 versus temperature data were analyzed on the basis of Woessner and Gutowsky model, and the activation energy for the reorientation of the CH3 group was estimated. The temperature dependence of the average torsional lifetimes of the molecules and the transition probabilities were also obtained. NQR frequency shows a nonlinear behavior with pressure, indicating both dynamic and static effects of pressure. The pressure coefficients were observed to be positive for both the lines. A thermodynamic analysis of the data was carried out to determine the constant volume temperature coefficients of the NQR frequency. The variation of spin lattice time with pressure was very small, showing that the relaxation is mainly due to the torsional motions of the molecules. Copyright (C) 2010 John Wiley & Sons, Ltd.

Wire-cylinder corona discharge with the wire at positive potential studies of iron oxides

A wire-cylinder corona discharge was studied in nitrogen and dry air in crossed electric and magnetic fields for values of magnetic field ranging from 0 to 3000 G with the wire at positive potential. In the absence of a magnetic field pre-onset streamers and pulses were observed in nitrogen. In both nitrogen and dry air breakdown streamers were observed just before spark breakdown of the gap. Furthermore, experiments in dry air at atmospheric pressure in an electric field indicate regular pre-onset streamers appearing at time intervals of 19.5 µs. The appearance of regular pre-onset streamers suggests that it is not possible for negative ions to form a sheath close to the anode as postulated by Hermstein (1960) for the formation of steady or glow corona in a point-plane gap.

Wire-cylinder corona discharge with the wire at positive potential

A wire-cylinder corona discharge was studied in nitrogen and dry air in crossed electric and magnetic fields for values of magnetic field ranging from 0 to 3000 G with the wire at positive potential. In the absence of a magnetic field pre-onset streamers and pulses were observed in nitrogen. In both nitrogen and dry air breakdown streamers were observed just before spark breakdown of the gap. Furthermore, experiments in dry air at atmospheric pressure in an electric field indicate regular pre-onset streamers appearing at time intervals of 19.5 µs. The appearance of regular pre-onset streamers suggests that it is not possible for negative ions to form a sheath close to the anode as postulated by Hermstein (1960) for the formation of steady or glow corona in a point-plane gap.

Development of atmospheric pressure ionization ion mobility spectrometry and ion mobility spectrometry mass spectrometry

This study is focused on the development and evaluation of ion mobility instrumentation with various atmospheric pressure ionization techniques and includes the following work. First, a high-resolution drift tube ion mobility spectrometer (IMS), coupled with a commercial triple quadrupole mass spectrometer (MS), was developed. This drift tube IMS is compatible with the front-end of commercial Sciex mass spectrometers (e.g., Sciex API-300, 365, and 3000) and also allows easy (only minor modifications are needed) installation between the original atmospheric pressure ion source and the triple quadrupole mass spectrometer. Performance haracteristics (e.g.,resolving power, detection limit, transmission efficiency of ions) of this IMS-MS instrument were evaluated. Development of the IMS-MS instrument also led to a study where a proposal was made that tetraalkylammonium ions can be used as chemical standards for ESI-IMS. Second, the same drift tube design was also used to build a standalone ion mobility spectrometer equipped with a Faraday plate detector. For this highresolution (resolving power about 100 shown) IMS device, a multi-ion source platform was built, which allows the use of a range of atmospheric pressure ionization methods, such as: corona discharge chemical ionization (CD-APCI), atmospheric pressure photoionization (APPI), and radioactive atmospheric pressure chemical ionization (R-APCI). The multi-ion source platform provides easy switching between ionization methods and both positive and negative ionization modes can be used. Third, a simple desorpion/ionization on silicon (DIOS) ion source set-up for use with the developed IMS and IMS-MS instruments was built and its operation demonstrated. Fourth, a prototype of a commercial aspiration-type ion mobility spectrometer was mounted in front of a commercial triple quadrupole mass spectrometer. The set-up, which is simple, easy to install, and requires no major modifications to the MS, provides the possibility of gathering fundamental information about aspiration mobility spectrometry.

Plasma diagnostics of the high pressure oxygen-sputtering process

The characteristics of the high pressure oxygen-sputtering plasma in the pressure range 0.8–2.4 mbar have been studied using the Langmuir probe technique. The variation in plasma parameters such as positive ion density, electron density, mean electron energy and floating potential with pressure and temperature has been investigated. It has been observed that the positive ion density increases at high substrate temperatures whereas the negative ion density decreases. The study of the variation in mean electron energy and floating potential also indicated the possibility that the number of negative ions is less when the substrates are at elevated temperatures. Since the negative ions are supposed to cause re-sputtering and make the films off-stoichiometric, the reduction in the negative ion density as observed at elevated substrate temperatures is better suited for depositing stoichiometric YBa2Cu3O7−δ superconducting thin films.

Variation of surface flashover voltage in SF6 with pressure

Surface flashover characteristics of solid spacers in a rod-plane configuration have been investigated in SF6, at pressures to 400 kPa, for switching impulse voltages to determine the effect of spacer, spacer materials and polarity of applied impulses. The effect of spacer material on the flashover voltage is not significant. For negative polarity impulses, the influence of the spacer is also insignificant. But for positive polarity impulses, at pressures < 200 kPa, the spacer efficiency becomes > 1.0. On the other hand, at pressures > 200 kPa, the presence of spacer drastically reduces the flashover voltage of the system. At about atmospheric pressure also, the spacer efficiency in air has been found to be > 1.0, with the same electrode geometry.

Passive pressure coefficients, critical failure surface and its kinematic admissibility

Using a combination of a logarithmic spiral and a straight line as a failure surface, comprehensive charts have been developed to determine the passive earth pressure coefficients and the positions of the critical failure surface for positive as well as negative wall friction angles. Translational movement of the wall has been examined in detail, considering the soil as either an associated flow dilatant material or a non-dilatant material, to determine the kinematic admissibility of the limit equilibrium solutions.

Cl-35 NQR frequency and spin lattice relaxation time in 3,4-dichlorophenol as a function of pressure and temperature

The pressure dependences of Cl-35 nuclear quadrupole resonance (NQR) frequency, temperature and pressure variation of spin lattice relaxation time (T-1) were investigated in 3,4-dichlorophenol. T-1 was measured in the temperature range 77-300 K. Furthermore, the NQR frequency and T-1 for these compounds were measured as a function of pressure up to 5 kbar at 300 K. The temperature dependence of the average torsional lifetimes of the molecules and the transition probabilities W-1 and W-2 for the Delta m = +/- 1 and Delta m = +/- 2 transitions were also obtained. A nonlinear variation of NQR frequency with pressure has been observed and the pressure coefficients were observed to be positive. A thermodynamic analysis of the data was carried out to determine the constant volume temperature coefficients of the NQR frequency. An attempt is made to compare the torsional frequencies evaluated from NQR data with those obtained by IR spectra. On selecting the appropriate mode from IR spectra, a good agreement with torsional frequency obtained from NQR data is observed. The previously mentioned approach is a good illustration of the supplementary nature of the data from IR studies, in relation to NQR studies of compounds in solid state.

Flame surface statistics of constant-pressure turbulent expanding premixed flames

In this paper we investigate the local flame surface statistics of constant-pressure turbulent expanding flames. First the statistics of local length ratio is experimentally determined from high-speed planar Mie scattering images of spherically expanding flames, with the length ratio on the measurement plane, at predefined equiangular sectors, defined as the ratio of the actual flame length to the length of a circular-arc of radius equal to the average radius of the flame. Assuming isotropic distribution of such flame segments we then convolute suitable forms of the length-ratio probability distribution functions (pdfs) to arrive at the corresponding area-ratio pdfs. It is found that both the length ratio and area ratio pdfs are near log-normally distributed and shows self-similar behavior with increasing radius. Near log-normality and rather intermittent behavior of the flame-length ratio suggests similarity with dissipation rate quantities which stimulates multifractal analysis. (C) 2014 AIP Publishing LLC.

Pressure Dependence of Glass Transition in As2Te3 Glass

Amorphous solids prepared from their melt state exhibit glass transition phenomenon upon heating. Viscosity, specific heat, and thermal expansion coefficient of the amorphous solids show rapid changes at the glass transition temperature (T-g). Generally, application of high pressure increases the T-g and this increase (a positive dT(g)/dP) has been understood adequately with free volume and entropy models which are purely thermodynamic in origin. In this study, the electrical resistivity of semiconducting As2Te3 glass at high pressures as a function of temperature has been measured in a Bridgman anvil apparatus. Electrical resistivity showed a pronounced change at T-g. The T-g estimated from the slope change in the resistivity-temperature plot shows a decreasing trend (negative dT(g)/dP). The dT(g)/dP was found to be -2.36 degrees C/kbar for a linear fit and -2.99 degrees C/kbar for a polynomial fit in the pressure range 1 bar to 9 kbar. Chalcogenide glasses like Se, As2Se3, and As30Se30Te40 show a positive dT(g)/dP which is very well understood in terms of the thermodynamic models. The negative dT(g)/dP (which is generally uncommon in liquids) observed for As2Te3 glass is against the predictions of the thermodynamic models. The Adam-Gibbs model of viscosity suggests a direct relationship between the isothermal pressure derivative of viscosity and the relaxational expansion coefficient. When the sign of the thermal expansion coefficient is negative, dT(g)/dP = Delta k/Delta alpha will be less than zero, which can result in a negative dT(g)/dP. In general, chalcogenides rich in tellurium show a negative thermal expansion coefficient (NTE) in the supercooled and stable liquid states. Hence, the negative dT(g)/dP observed in this study can be understood on the basis of the Adams-Gibbs model. An electronic model proposed by deNeufville and Rockstad finds a linear relation between T-g and the optical band gap (E-g for covalent semiconducting glasses when they are grouped according to their average coordination number. The electrical band gap (Delta E) of As2Te3 glass decreases with pressure. The optical and electrical band gaps are related as Delta E-g = 2 Delta E; thus, a negative dT(g)/dP is expected when As2Te3 glass is subjected to high pressures. In this sense, As2Te3 is a unique glass where its variation of T-g with pressure can be understood by both electronic and thermodynamic models.

Dynamics of intermittent force fluctuations in vesicular nanotubulation

Irregular force fluctuations are seen in most nanotubulation experiments. The dynamics behind their presence has, however, been neither commented upon nor modeled. A simple estimate of the mean energy dissipated in force drops turns out to be several times the thermal energy. This coupled with the rate dependent nature of the deformation reported in several experiments point to a dynamical origin of the serrations. We simplify the whole process of tether formation through a three-stage model of successive deformations of sphere to ellipsoid, neck-formation, and tubule birth and extension. Based on this, we envisage a rate-softening frictional force at the neck that must be overcome before a nanotube can be pulled out. Our minimal model includes elastic and visco-elastic deformation of the vesicle, and has built-in dependence on pull velocity, vesicle radius, and other material parameters, enabling us to capture various kinds of serrated force-extension curves for different parameter choices. Serrations are predicted in the nanotubulation region. Other features of force-extension plots reported in the literature such as a plateauing serrated region beyond a force drop, serrated flow region with a small positive slope, an increase in the elastic threshold with pull velocity, force-extension curves for vesicles with larger radius lying lower than those for smaller radius, are all also predicted by the model. A toy model is introduced to demonstrate that the role of the friction law is limited to inducing stick-slip oscillations in the force, and all other qualitative and quantitative features emerging from the model can only be attributed to other physical mechanisms included in the deformation dynamics of the vesicle. (C) 2014 AIP Publishing LLC.

Peristaltic pump-based low range pressure sensor calibration system

Peristaltic pumps were normally used to pump liquids in several chemical and biological applications. In the present study, a peristaltic pump was used to pressurize the chamber (positive as well negative pressures) using atmospheric air. In the present paper, we discuss the development and performance study of an automatic pressurization system to calibrate low range (millibar) pressure sensors. The system includes a peristaltic pump, calibrated pressure sensor (master sensor), pressure chamber, and the control electronics. An in-house developed peristaltic pump was used to pressurize the chamber. A closed loop control system has been developed to detect and adjust the pressure leaks in the chamber. The complete system has been integrated into a portable product. The system performance has been studied for a step response and steady state errors. The system is portable, free from oil contaminants, and consumes less power compared to existing pressure calibration systems. The veracity of the system was verified by calibrating an unknown diaphragm based pressure sensor and the results obtained were satisfactory. (C) 2015 AIP Publishing LLC.

The positive floating potential of high-temperature particles in plasma

It has been predicted that the floating potential of particles in plasma may become positive when the particle surface temperature is high enough, but, to our knowledge, no positive floating potential has been obtained yet. In the present paper the floating potential theory of high-temperature particles in plasma is developed to cover the positive potential range for the first time, and a general approximate analytical formula for the positive floating potential with a thin plasma sheath and subsonic plasma flow is derived from the new model recently proposed by the authors. The results show that when the floating potential is positive, the net flux of charge incident on the particle approaches a constant similar to the 'electron saturation' phenomena in the case of the electric probes.