Biomedical subjects

Joseph L Bull

Publications and source records attributed to Joseph L Bull.

17 recordsLinked to original sources

PubMed2006

Microbubble expansion in a flexible tube.

We have utilized a computational model of the expansion of a microbubble in a liquid-filled flexible tube to investigate the potential for acoustic vaporization of perfluorocarbon droplets to damage blood vessels during a novel gas embolotherapy technique for the potential treatment of tumors. This model uses a fixed grid, multi-domain, interface tracking, direct numerical simulation method that treats all interfaces and boundaries as sharp discontinuities for high accuracy. In the current work, we examined effects of initial bubble size on the flows and wall stresses that result from droplet vaporization. The remaining dimensionless parameters that govern the system response (Reynolds, Weber, and Strouhal numbers, initial bubble pressure, and wall stiffness and tension) were selected to model an arteriole. The results for a flexible tube are significantly different from those for a rigid tube. Two major flow regimes occur due to the combined effect of bubble and tube deformation: in flow at the tube ends and out flow near the bubble surface. The flexibility of the tube largely dissipates the extreme pressure that develops in the rigid tube model. Both the magnitude and the overall expansion time of the rapidly changing pressure are greatly reduced in the flexible tube. Smaller initial bubble diameters, relative to the vessel diameter, result in lower wall stresses. This study indicates that wall flexibility can significantly influence the wall stresses that result from acoustic vaporization of intravascular perfluorocarbon droplets, and suggests that acoustic activation of droplets in larger, more flexible vessels may be less likely to damage or rupture vessels than activation in smaller and stiffer vessels.

Animals↗

PubMed2006

Effect of viscosity on instilled perfluorocarbon distribution in rabbit lungs.

The effect of viscosity on the distribution of perfluorocarbon instilled into the lungs for liquid ventilation was investigated. Perfluorocarbon (either perfluorodecalin or FC-3283) was instilled into the trachea during ventilation at a constant infusion rate of 40 ml/min and radiographic images were obtained at 30 frames/s. Image analysis was performed and the homogeneity index of the distribution was computed for images at the end of inspiration of each breath to evaluate the evolution of perfluorocarbon distribution during filling. The higher viscosity perfluorocarbon (perfluorodecalin) resulted in a more homogeneous distribution. This was attributed to perfluorodecalin's higher propensity to form liquid plugs in large airways and to those plugs leaving behind a thicker liquid layer as they propagated through the lungs.

Animals↗

PubMed2006

Refinements in mathematical models to predict aneurysm growth and rupture.

The growth of aneurysms and eventually their likelihood of rupture depend on the determination of the stress and strain within the aneurysm wall and the exact reproduction of its geometry. A numerical model is developed to analyze pulsatile flow in abdominal aortic aneurysm (AAA) models using real physiological resting and exercise waveforms. Both laminar and turbulent flows are considered. Interesting features of the flow field resulting from using realistic physiological waveforms are obtained for various parameters using finite element methods. Such parameters include Reynolds number, size of the aneurysm (D/d), and flexibility of the aneurysm wall. The effect of non-Newtonian behavior of blood on hemodynamic stresses is compared with Newtonian behavior, and the non-Newtonian effects are demonstrated to be significant in realistic flow situations. Our results show that maximum turbulent fluid shear stress occurs at the distal end of the AAA model. Furthermore, turbulence is found to have a significant effect on the pressure distribution along AAA wall for both physiological waveforms. Related experimental work in which a bench top aneurysm model is developed is also discussed. The experimental model provides a platform to validate the numerical model. This work is part of our ongoing development of a patient-specific tool to guide clinician decision making and to elucidate the contribution of blood flow-induced stresses to aneurysm growth and eventual rupture. These studies indicate that accurately modeling the physiologic features of real aneurysms and blood is paramount to achieving our goal.

Aneurysm↗

PubMed2006

Modeling pulsatile flow in aortic aneurysms: effect of non-Newtonian properties of blood.

Pulsatile flow in an axisymmetric rigid-walled model of an abdominal aorta aneurysm was analyzed numerically for various aneurysm dilations using physiologically realistic resting waveform at time-averaged Reynolds number of 300 and peak Reynolds number of 1607. Discretization of the governing equations was achieved using a finite element scheme based on the Galerkin method of weighted residuals. Comparisons with previously published work on the basis of special cases were performed and found to be in excellent agreement. Our findings indicate that the velocity fields are significantly affected by non-Newtonian properties in pathologically altered configurations. Non-Newtonian fluid shear stress is found to be greater than Newtonian fluid shear stress during peak systole. Further, the maximum shear stress is found to occur near the distal end of AAA during peak systole. The impact of non-Newtonian blood flow characteristics on pressure compared to Newtonian model is found insignificant under resting conditions. Viscous and inertial forces associated with blood flow are responsible for the changes in the wall that result in thrombus deposition and dilation while rupture of AAA is more likely determined by much larger mechanical stresses imposed by pulsatile pressure on the wall of AAA.

Aortic Aneurysm, Abdominal↗

PubMed2005

Bubble splitting in bifurcating tubes: a model study of cardiovascular gas emboli transport.

The transport of long gas bubbles, suspended in liquid, through symmetric bifurcations, is investigated experimentally and theoretically as a model of cardiovascular gas bubble transport in air embolism and gas embolotherapy. The relevant dimensionless parameters in the models match the corresponding values for arteries and arterioles. The effects of roll angle (the angle the plane of the bifurcation makes with the horizontal), capillary number (a dimensionless indicator of flow), and bubble volume (or length) on the splitting of bubbles as they pass through the bifurcation are examined. Splitting is observed to be more homogenous at higher capillary numbers and lower roll angles. It is shown that, at nonzero roll angles, there is a critical value of the capillary number below which the bubbles do not split and are transported entirely into the upper branch. The value of the critical capillary number increases with roll angle and parent tube diameter. A unique bubble motion is observed at the critical capillary number and for slightly slower flows: the bubble begins to split, the meniscus in the lower branch then moves backward, and finally the entire bubble enters the upper branch. These findings suggest that, in large vessels, emboli tend to be transported upward unless flow is unusually strong but that a more homogeneous distribution of emboli occurs in smaller vessels. This corresponds to previous observations that air emboli tend to lodge in the upper regions of the lungs and suggests that relatively uniform infarction of tumors by gas embolotherapy may be possible.

Animals↗

PubMed2005

A theoretical model of a molecular-motor-powered pump.

The motion of a cylindrical bead in a fluid contained within a two-dimensional channel is investigated using the boundary element method as a model of a biomolecular-motor-powered microfluidics pump. The novelty of the pump lies in the use of motor proteins (kinesin) to power the bead motion and the few moving parts comprising the pump. The performance and feasibility of this pump design is investigated using two model geometries: a straight channel, and a curved channel with two concentric circular walls. In the straight channel geometry, it is shown that increasing the bead radius relative to the channel width, increases the flow rate at the expense of increasing the force the kinesins must generate in order to move the bead. Pump efficiency is generally higher for larger bead radii, and larger beads can support higher imposed loads. In the circular channel geometry, it is shown that bead rotation modifies the force required to move the bead and that shifting the bead inward slightly reduces the required force. Bead rotation has a minimal effect on flow rate. Recirculation regions, which can develop between the bead and the channel walls, influence the stresses and force on the bead. These results suggest this pump design is feasible, and the kinesin molecules provide sufficient force to deliver pico- to atto- l/s flows.

Computer Simulation↗

PubMed2005

Flow limitation in liquid-filled lungs: effects of liquid properties.

Flow limitation in liquid-filled lungs is examined in intact rabbit experiments and a theoretical model. Flow limitation ("choked" flow) occurs when the expiratory flow reaches a maximum value and further increases in driving pressure do not increase the flow. In total liquid ventilation this is characterized by the sudden development of excessively negative airway pressures and airway collapse at the choke point. The occurrence of flow limitation limits the efficacy of total liquid ventilation by reducing the minute ventilation. In this paper we investigate the effects of liquid properties on flow limitation in liquid-filled lungs. It is found that the behavior of liquids with similar densities and viscosities can be quite different. The results of the theoretical model, which incorporates alveolar compliance and airway resistance, agrees qualitatively well with the experimental results. Lung compliance and airway resistance are shown to vary with the perfluorocarbon liquid used to fill the lungs. Surfactant is found to modify the interfacial tension between saline and perfluorocarbon, and surfactant activity at the interface of perfluorocarbon and the native aqueous lining of the lungs appears to induce hysteresis in pressure-volume curves for liquid-filled lungs. Ventilation with a liquid that results in low viscous resistance and high elastic recoil can reduce the amount of liquid remaining in the lungs when choke occurs, and, therefore, may be desirable for liquid ventilation.

Airway Resistance↗

PubMed2005

Cardiovascular bubble dynamics.

Gas bubbles can form in the cardiovascular system as a result of patho-physiological conditions or can be intentionally introduced for diagnostic or therapeutic reasons. The dynamic behavior of these bubbles is caused by a variety of mechanisms, such as inertia, pressure, interfacial tension, viscosity, and gravity. We review recent advances in the fundamental mechanics and applications of cardiovascular bubbles, including air embolism, ultrasound contrast agents, targeted microbubbles for drug delivery and molecular imaging, cavitation-induced tissue erosion for ultrasonic surgery, microbubble-induced angiogenesis and arteriogenesis, and gas embolotherapy.

Animals↗

PubMed2004

Effect of ventilation rate on instilled surfactant distribution in the pulmonary airways of rats.

Liquid can be instilled into the pulmonary airways during medical procedures such as surfactant replacement therapy, partial liquid ventilation, and pulmonary drug delivery. For all cases, understanding the dynamics of liquid distribution in the lung will increase the efficacy of treatment. A recently developed imaging technique for the study of real-time liquid transport dynamics in the pulmonary airways was used to investigate the effect of respiratory rate on the distribution of an instilled liquid, surfactant, in a rat lung. Twelve excised rat lungs were suspended vertically, and a single bolus (0.05 ml) of exogenous surfactant (Survanta, Ross Laboratories, Columbus, OH) mixed with radiopaque tracer was instilled as a plug into the trachea. The lungs were ventilated with a 4-ml tidal volume for 20 breaths at one of two respiratory rates: 20 or 60 breaths/min. The motion of radiodense surfactant was imaged at 30 frames/s with a microfocal X-ray source and an image intensifier. Dynamics of surfactant distribution were quantified for each image by use of distribution statistics and a homogeneity index. We found that the liquid distribution depended on the time to liquid plug rupture, which depends on ventilation rate. At 20 breaths/min, liquid was localized in the gravity-dependent region of the lung. At 60 breaths/min, the liquid coated the airways, providing a more vertically uniform liquid distribution.

Algorithms↗

PubMed2004

A prototype of a liquid ventilator using a novel hollow-fiber oxygenator in a rabbit model.

OBJECTIVE: A functional total liquid ventilator should be simple in design to minimize operating errors and have a low priming volume to minimize the amount of perfluorocarbon needed. Closed system circuits using a membrane oxygenator have partially met these requirements but have high resistance to perfluorocarbon flow and high priming volume. To further this goal, a single piston prototype ventilator with a low priming volume and a new high-efficiency hollow-fiber oxygenator in a circuit with a check valve flow control system was developed. DESIGN: Prospective, controlled animal laboratory study. SETTING: Research facility at a university medical center. SUBJECTS: Seven anesthetized, paralyzed, normal New Zealand rabbits INTERVENTIONS: The prototype oxygenator, consisting of cross-wound silicone hollow fibers with a surface area of 1.5 m2 with a priming volume of 190 mL, was tested in a bench-top model followed by an in vivo rabbit model. Total liquid ventilation was performed for 3 hrs with 20 mL.kg(-1) initial fill volume, 17.5-20 mL.kg(-1) tidal volume, respiratory rate of 5 breaths/min, inspiratory/expiratory ratio 1:2, and countercurrent sweep gas of 100% oxygen. MEASUREMENTS AND MAIN RESULTS: Bench top experiments demonstrated 66-81% elimination of CO2 and 0.64-0.76 mL.min(-1) loss of perfluorocarbon across the fibers. No significant changes in PaCO2 and PaO2 were observed. Dynamic airway pressures were in a safe range in which ventilator lung injury or airway closure was unlikely (3.6 +/- 0.5 and -7.8 +/- 0.3 cm H2O, respectively, for mean peak inspiratory pressure and mean end expiratory pressure). No leakage of perfluorocarbon was noted in the new silicone fiber gas exchange device. Estimated in vivo perfluorocarbon loss from the device was 1.2 mL.min(-1). CONCLUSIONS: These data demonstrate the ability of this novel single-piston, nonporous hollow silicone fiber oxygenator to adequately support gas exchange, allowing successful performance of total liquid ventilation.

Animals↗

PubMed2004

Direct numerical simulations of micro-bubble expansion in gas embolotherapy.

We are currently developing a novel gas embolotherapy technique that involves the selective, acoustic vaporization of liquid perfluorocarbon droplets in or near a tumor as a possible treatment for cancer The resulting bubbles can then stick within the tumor vasculature to occlude blood flow and "starve" the tumor The potential development of high stresses during droplet vaporization is a major concern for safe implementation of this technique. No prior study, either experimentally or theoretically, addresses this important issue. In this work, the acoustic vaporization procedure of the therapy is investigated by direct numerical simulations. The nonlinear, multiphase, computational model is comprised of an ideal gas bubble surrounded by liquid inside a long tube. Convective and unsteady inertia, viscosity, and surface tension affect the bubble dynamics and are included in this model, which is solved by a novel fixed-grid, sharp-interface, moving boundary method. We assess the potential for flow-induced wall stresses to rupture the vessel or damage the endothelium during vaporization under a range of operating conditions by varying dimensionless parameters--Reynolds, Weber, and Strouhal numbers, inertial energy and initial droplet size. It is found that the wall pressure is typically highest at the start of the bubble expansion, but the maximum wall shear stress occurs at a later time. Smaller initial bubble diameters, relative to the vessel diameter, result in lower wall stresses.

Blood Flow Velocity↗

PubMedDate not supplied

Design of an artificial lung compliance chamber for pulmonary replacement.

Matching the impedance of an artificial lung for pulmonary replacement to native pulmonary impedance is important in preventing right ventricular dysfunction. A lumped-parameter theoretical model and bench-top experiments were used to investigate the effect of a prototype compliance chamber on input impedance. The bench-top simulation consisted of a pulsatile flow generator, a prototype compliance chamber, and a low resistance artificial lung connected in series. Effective compliance was varied using pneumatic compression. The theoretical model considered a similar circuit with resistors before and after a compliance element. The bundle flow pulsatility (flow amplitude divided by average flow) and input impedance were calculated in the theoretical and experimental models. More compliance and lower upstream resistance result in lower bundle flow pulsatility and reduced first harmonic impedance. Matching the time scale of the circuit to the period of pulsatile flow also reduces impedance. The bench-top circuit demonstrated an optimal chamber pressure at which first harmonic impedance is reduced by 80%. The prototype compliance chamber in series with the artificial lung more closely matches native pulmonary impedance. The lumped-parameter model and the bench-top simulation will aid in the design and testing of compliance chamber modifications to improve its efficiency.

Artificial Organs↗

PubMedDate not supplied

Total liquid ventilation: dynamic airway pressure and the development of expiratory flow limitation.

Expiratory flow limitation occurs during total liquid ventilation (TLV), and is characterized by the sudden development of excessively negative intratracheal pressures without increases in flow. The purpose of this study was to identify a dynamic signal for the servoregulation of expiratory flow (Ve), by determining the range of dynamic intratracheal pressures [P(T)], which mark the onset of flow limitation during liquid expiration, where choke occurs at the critical pressure (Pc). The lungs of rabbits were filled with perflurocarbon to an end-inspiratory lung volume (EILV) of 20, 30, or 40cc/kg and connected to a piston driven liquid ventilator, which removed perfluorocarbon at a rate (Vs) of 2.5, 5.0, or 7.5 ml/s. Nine animals per EILV group were used (27 animals total), and within each EILV group each (Vs) was used three times. P(T) and (Ve) (T) were measured at the tracheostomy tube, and dP/dT was calculated from P(T). Pc was determined within each EILV/(Vs) group by examining the average dP/dT curve for the first significant change from baseline. Pc ranged from -6.02 +/- 1.83 to -9.02 +/- 3.2 mm Hg. In general, the higher the EILV, the more negative the Pc. We conclude that Pc during TLV varies within a limited range in rabbits. These data may be used to maximize expired volume during TLV by sequentially tapering flow rates as this critical range of pressures is approached.

Animals↗

PubMedDate not supplied

Location of flow limitation in liquid-filled rabbit lungs.

The effects of end-inspiratory lung volume (EILV) and expiratory flow rate (Q) on the location of flow limitation in liquid-filled lungs were investigated by measuring pressure along the airways and by radiographic imaging. The lungs of New Zealand white rabbits were filled with perfluorocarbon to the randomly selected EILV of 20, 30, or 40 ml/kg, and the volume was actively drained at one of three Q: 2.5, 5.0, or 7.5 ml/s. The minimum pressures recorded by a movable catheter at locations along the airways show that flow limitation occurred in the main bronchi and trachea, and was independent of EILV and Q. The minimum pressure at the trachea was -80 mm Hg compared with values that were more positive than -10 mm Hg at a location 3 cm distal to the carina for all EILV and Q combinations. This location was confirmed by the lung images. The airway diameters gradually decreased with time, until flow limitation occurred. In airways distal to the collapse, there was not a significant decrease in diameter. Based on these data, we conclude that flow limitation in liquid-filled lungs occurs in the trachea and main bronchi and its location is independent of EILV or Q.

Animals↗

PubMedDate not supplied

Expiratory flow limitation during gravitational drainage of perfluorocarbons from liquid-filled lungs.

Flow limitation during pressure-driven expiration in liquid-filled lungs was examined in intact, euthanized New Zealand white rabbits. The aim of this study was to further characterize expiratory flow limitation during gravitational drainage of perfluorocarbon liquids from the lungs, and to study the effect of perfluorocarbon type and negative mouth pressure on this phenomenon. Four different perfluorocarbons (PP4, perfluorodecalin, perfluoro-octyl-bromide, and FC-77) were used to examine the effects of density and kinematic viscosity on volume recovered and maximum expiratory flow. It was demonstrated that flow limitation occurs during gravitational drainage when the airway pressure is < or = -15 cm H(2)O, and that this critical value of pressure did not depend on mouth pressure or perfluorocarbon type. The perfluorocarbon properties affect the volume recovered, maximum expiratory flow, and the time to drain, with the most viscous perfluorocarbon (perfluorodecalin) taking the longest time to drain and resulting in lowest maximum expiratory flow. Perfluoro-octyl-bromide resulted in the highest recovered volume. The findings of this study are relevant to the selection of perfluorocarbons to reduce the occurrence of flow limitation and provide adequate minute ventilation during total liquid ventilation.

Animals↗

PubMedDate not supplied

Effect of artificial lung compliance on right ventricular load.

Artificial lungs may serve as transplant alternatives to patients with respiratory failure. To provide a pulmonary replacement, the device cannot significantly alter right ventricular afterload. We sought to characterize cardiac load using a prototype artificial lung as a pulmonary replacement. An artificial lung was implanted into 13 adult sheep, 7 using a noncompliant original prototype and 6 using a modified device with a compliance chamber. Inflow was from the pulmonary artery and outflow into the left atrium. Pulmonary impedance was determined and pulse wave reflections analyzed. Resistance was similar in the original prototype artificial lung and in the native pulmonary circulation (3.0 vs 3.2 Woods units, p = 0.5). First harmonic impedance was significantly increased in the original prototype artificial lung (0.4 vs 5.9 Woods units, p < 0.01). High-amplitude pulse wave reflections were identified and right ventricular function was altered. The addition of compliance to the artificial lung reduced impedance at the first harmonic (5.9 vs 1.9 Woods units, p < 0.01), decreased the amplitude of pulse wave reflections, and normalized right ventricular function. A low-resistance but noncompliant artificial lung increases pulmonary impedance and alters right ventricular function. Addition of a compliance chamber reduces pulse wave reflections and normalizes ventricular function.

Animals↗

PubMedDate not supplied

Pulsatile flow past a cylinder: an experimental model of flow in an artificial lung.

The focus of this study is an experimental apparatus that serves as a model for studying blood flow in a total artificial lung (TAL), a prototype device intended to serve as a bridge to lung transplantation or that supports pulmonary function during the treatment of severe respiratory failure. The TAL consists of hollow cylindrical fibers that oxygen-rich air flows through and oxygen-poor blood flows around. Because gas diffusivity in the TAL is very small, a convection mechanism dominates the gas transport, which is why we focus on the velocity around the fibers (modeled as a 0.05-cm-in-diameter and 5-cm-long cylinder). We designed a low-speed water tunnel to study the flow mechanism around the cylinder, across which the flow is generated by a linear actuator that allows different flow patterns to mimic the flow in a TAL. We tested the flow in the test section by numerical simulation and by the particle image velocimetry method to study the flow profile. The results show a uniform flow near the centerline of the water tunnel where the cylinder is placed. This decreases the effects of free-stream turbulence in the shear layers and reduces the uncertainty in determining the flow patterns around the cylinder. Knowledge gained from the flow around one cylinder (fiber) is beneficial for understanding vortex formation around multiple cylinders. We present a summary of vortex formation behind a cylinder for Reynolds numbers (Re) of 1, 3, and 5 and Stokes numbers (Ns) of 0.18 to 0.37; results show that higher Re and Ns favor vortex formation. These findings regarding the parameter range for vortex formation may provide principles for designing artificial lungs to enhance convective mixing. We anticipate that the pulsatile flow circuit presented here can be used to mimic the flow not only in TALs but in other physiological systems.

Animals↗