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Biomedical subjects

R D Kamm

Publications and source records attributed to R D Kamm.

At least 37 records · Page 2Linked to original sources
PubMed2000

Numerical analysis of blood flow through a stenosed artery using a coupled, multiscale simulation method.

A global system model of the systemic circulation is combined with a local finite element solution to simulate blood flow in a stenosed coronary artery. Local fluid dynamic issues arise in connection with the detailed flow patterns within the stenosed coronary artery while the global system model is used to simulate the response of the rest of the circulation to the local perturbation. A PISO type finite element technique is employed to compute the local blood flow. The Navier-Stokes equations are solved with the assumption of viscous incompressible flow across the stenosed coronary artery. A detailed lumped parameter model simulates the characteristics of the coronary circulation and is imbedded in a coarse-grained lumped parameter model of the entire cardiovascular system. These two methods are coupled in that the lumped parameter calculations provide the time-dependent boundary conditions for the local finite element calculation. In turn, the local fluid dynamical computation provides estimates for the pressure drop across the stenosis, which is subsequently used to refine the lumped parameter calculation. Results are obtained for an axisymmetric coronary artery model with a stenosis of 90% area reduction over one cardiac cycle. Numerical results show that the flow rate and resistance are strongly coupled. Compared with the flow rate distribution computed from the global simulation with constant resistance, the coupled solution predicts a flow rate with only slight changes. The high flow rate during diastole increases the stenosis pressure drop and resistance. In turn, this increased resistance of the stenosis slightly reduces the flow rate computed in the lumped parameter simulation.

Arteries↗
PubMed1999

A fluid--structure interaction finite element analysis of pulsatile blood flow through a compliant stenotic artery.

A new model is used to analyze the fully coupled problem of pulsatile blood flow through a compliant, axisymmetric stenotic artery using the finite element method. The model uses large displacement and large strain theory for the solid, and the full Navier-Stokes equations for the fluid. The effect of increasing area reduction on fluid dynamic and structural stresses is presented. Results show that pressure drop, peak wall shear stress, and maximum principal stress in the lesion all increase dramatically as the area reduction in the stenosis is increased from 51 to 89 percent. Further reductions in stenosis cross-sectional area, however, produce relatively little additional change in these parameters due to a concomitant reduction in flow rate caused by the losses in the constriction. Inner wall hoop stretch amplitude just distal to the stenosis also increases with increasing stenosis severity, as downstream pressures are reduced to a physiological minimum. The contraction of the artery distal to the stenosis generates a significant compressive stress on the downstream shoulder of the lesion. Dynamic narrowing of the stenosis is also seen, further augmenting area constriction at times of peak flow. Pressure drop results are found to compare well to an experimentally based theoretical curve, despite the assumption of laminar flow.

Arteries↗
PubMed1999

The effects of external compression on venous blood flow and tissue deformation in the lower leg.

External pneumatic compression of the lower legs is effective as prophylaxis against deep vein thrombosis. In a typical application, inflatable cuffs are wrapped around the patient's legs and periodically inflated to prevent stasis, accelerate venous blood flow, and enhance fibrinolysis. The purpose of this study was to examine the stress distribution within the tissues, and the corresponding venous blood flow and intravascular shear stress with different external compression modalities. A two-dimensional finite element analysis (FEA) was used to determine venous collapse as a function of internal (venous) pressure and the magnitude and spatial distribution of external (surface) pressure. Using the one-dimensional equations governing flow in a collapsible tube and the relations for venous collapse from the FEA, blood flow resulting from external compression was simulated. Tests were conducted to compare circumferentially symmetric (C) and asymmetric (A) compression and to examine distributions of pressure along the limb. Results show that A compression produces greater vessel collapse and generates larger blood flow velocities and shear stresses than C compression. The differences between axially uniform and graded-sequential compression are less marked than previously found, with uniform compression providing slightly greater peak flow velocities and shear stresses. The major advantage of graded-sequential compression is found at midcalf. Strains at the lumenal border are approximately 20 percent at an external pressure of 50 mmHg (6650 Pa) with all compression modalities.

Blood Flow Velocity↗
PubMed1999

Airway wall mechanics.

The dimensions, composition, and stiffness of the airway wall are important determinants of airway cross-sectional area during dynamic collapse in a forced expiration or when airway smooth muscle is constricted. Under these circumstances, airway caliber is determined by an interaction between the forces acting to open the airway (parenchymal tension and wall stiffness) and those acting to close it (smooth-muscle force and surface tension at the inner gas-liquid interface). Experimental measurements and theoretical models of the airway tube law (relationship between cross-sectional area and transmural pressure) are presented. Data are presented for the elastic properties of the wall tissue. Simulations of airway constriction in normal and asthmatic airways are discussed. To the extent possible, comparisons are presented between the various models and existing experimental data.

Animals↗
PubMed1999

Bolus dispersal through the lungs in surfactant replacement therapy.

A model is presented of surfactant replacement therapy. An instilled bolus is pushed into the lungs on the first inspiration, coating the airways with a layer of surfactant and depositing some in the alveoli. Layer thickness depends on the capillary number (muU/gamma, where mu, U, and gamma are bolus viscosity, advancing meniscus velocity, and surface tension, respectively). Larger capillary number leads to thicker layers, reducing alveolar delivery. Subsequently, surface tension gradients sweep surfactant into alveoli not receiving surfactant during the first inspiration. The effects on spreading of sorption kinetics, bolus viscosity, initial layer thickness, initial penetration of surfactant, gravity, and shear stress are examined. Sorption nearly eliminates surface tension gradients in central airways but produces a sharp transition at the leading edge of the exogenous layer. Local thinning of the liquid layer results, trapping 95% of the surfactant in the airways. Gravity and ventilation augment transport somewhat. Transport to the periphery takes 4-170 s for the leading edge but considerably longer for the bulk of the surfactant. The model demonstrates how the various physical parameters governing surfactant distribution might alter the response to surfactant replacement therapy.

Adsorption↗
PubMed1999

Biophysical characterization and modeling of lung surfactant components.

The present study characterizes the dynamic interfacial properties of calf lung surfactant (CLS) and samples reconstituted in a stepwise fashion from phospholipid (PL), hydrophobic apoprotein (HA), surfactant apoprotein A (SP-A), and neutral lipid fractions. Dipalmitoylphosphatidylcholine (DPPC), the major PL component of surfactant, was examined for comparison. Surface tension was measured over a range of oscillation frequencies (1-100 cycles/min) and bulk phase concentrations (0.01-1 mg/ml) by using a pulsating bubble surfactometer. Distinct differences in behavior were seen between samples. These differences were interpreted by using a previously validated model of surfactant adsorption kinetics that describes function in terms of 1) adsorption rate coefficient (k1), 2) desorption rate coefficient (k2), 3) minimum equilibrium surface tension (gamma*), 4) minimum surface tension at film collapse (gammamin), and 5) change in surface tension with interfacial area for gamma < gamma* (m2). Results show that DPPC and PL have k1 and k2 values several orders of magnitude lower than CLS. PL had a gammamin of 19-20 dyn/cm, significantly greater than CLS (nearly zero). Addition of the HA to PL restored dynamic interfacial behavior to nearly that of CLS. However, m2 remained at a reduced level. Addition of the SP-A to PL + HA restored m2 to a level similar to that of CLS. No further improvement in function occurred with the addition of the neutral lipid. These results support prior studies that show addition of HA to the PL markedly increases adsorption and film stability. However, SP-A is required to completely normalize dynamic behavior.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

Computational models of cardiovascular function for analysis of post-flight orthostatic intolerance.

The work presented in this paper is part of an ongoing effort to use mathematical models to investigate the effects of microgravity on the cardiovascular system. In particular, a thirteen compartment lumped parameter representation of the cardiovascular system is used to simulate some of the current hypotheses concerning the mechanism of post-flight orthostatic intolerance. Simulations are compared to astronaut stand test data pre - and post-flight in an effort to quantitatively evaluate alternative hypotheses.

Aerospace Medicine↗
PubMed1998

Performance analysis of a cardiac assist device in counterpulsation.

Performance of a cardiac assist device pumping chamber in counterpulsation was evaluated using numerical simulations of the unsteady, three-dimensional flow inside the chamber and an analytical model of the force required to eject and fill the chamber. The wall shear stress within the device was similarly computed and modeled. The analytical model was scaled to match the numerical results and then used to predict performance at physiological operating conditions. According to these models for a stroke volume of 70 ml, between 0.4 and 1.0 W is required for counterpulsation at a frequency of 1.33 Hz against a restorative spring, depending on the spring constant chosen. The power and the maximum force calculated are within the ranges a trained skeletal muscle is capable of providing. Shear stress predictions show that platelet activation in the absence of surface effects and hemolysis due to high shear are unlikely to occur with this design. Furthermore, vortices that develop in the chamber during filling are predicted to increase blood mixing and provide favorable washing of the chamber walls. A computational-analytical approach such as this may have potential to aid rapid performance evaluation of new devices and streamline the design optimization process.

Counterpulsation↗
PubMed1998

Meniscus formation during tracheal instillation of surfactant.

The method of surfactant instillation into the lungs for treatment of neonatal respiratory distress syndrome is an important attribute of delivery, and it may determine the overall efficacy of treatment. Previous studies primarily focused on the rate at which the bolus is instilled. These findings show that rapid injections lead to a more homogenous distribution, whereas slow infusions drain into the dependent lung with respect to gravity, resulting in a heterogeneous deposition. These results suggest that it is beneficial to form a meniscus, from which a more homogenous dispersal can proceed. The objective of the present study was to develop a functional criterion for meniscus formation during bolus injection. An in vitro experiment was used to examine the clinical setting of surfactant instillation. The physical variables examined were the bolus viscosity (mu) and density (rho), gravity (g), injection rate (Q), orientation of the trachea with respect to gravity (theta), tracheal size (D), surface tension (gamma), and catheter size (d). All quantities were varied, except gravity and catheter size. Experimental results show that a meniscus will form when NSt > 0. 004Re2/3, where NSt is Stokes number and Re is Reynolds number, NSt = muQ/D4rhogsintheta, a ratio of viscous effects to gravitational effects, and Re = rhoQD/d2mu, a ratio of inertial effects to viscous effects. Rapid injections, high viscosity, and small inclination with respect to gravity promote meniscus formation. These results can be used to refine the guidelines for administration of surfactant replacement therapy.

Algorithms↗
PubMed1998

Mechanical properties of a self-assembling oligopeptide matrix.

We have begun studies of a novel type of biomaterial derived from a recently-discovered class of ionic self-complementary oligopeptides. These short peptides (typically 8, 16, 24, or 32 amino acid residues with internally-repeating sequences) self-assemble in aqueous salt solution into three-dimensional matrices capable of favorable interactions with cells, and offer promise for useful bioengineering design based on rational changes in sequence. In this paper we present preliminary results on mechanical properties, combining experimental and theoretical approaches, of one particular example of these peptide materials, EFK8. The static elastic modulus was measured using an apparatus designed to allow sample fabrication and mechanical testing in the same system with the sample in aqueous solution. The material microstructure was examined by SEM and the measurements interpreted with the aid of a model for cellular solids. Values for the elastic modulus increased from 1.59 +/- 0.06 to 14.7 +/- 1.0 kPa for peptide concentrations increasing from 2.7 to 10 mg ml-1. SEM photographs showed the microstructure to consist of a relatively homogeneous lattice with fiber thickness of 10-30 nm independent of peptide concentration, but with fiber density increasing with peptide concentration. This behavior is consistent with scaling predictions from the cellular solids model and yields an estimate for the individual fiber elastic modulus in the range of 1-20 MPa. We therefore have provided some initial physical principles for guiding improvement of the mechanical properties of these new materials.

Biomechanical Phenomena↗
PubMed1997

The non-uniform distribution of albumin in human and bovine cornea.

In our previous studies, we noted a non-uniform distribution of protein tracer preferentially entering the anterior stromal lamellae of the cornea from the limbus. Given other differences reported previously between the anterior and posterior lamellae of the cornea, and the number of corneal disorders in which abnormalities are preferentially confined to either the anterior or posterior lamellae, we were prompted to examine the distribution of albumin in normal human and bovine cornea. The distribution of albumin in bovine and human cornea was studied immunohistochemically. Total soluble protein and albumin in the anterior 1/3 and posterior 2/3 of the central, middle and peripheral cornea of bovine eyes was measured biochemically. To aid in interpreting the findings, a theoretical model was developed based upon the combined effects of diffusive and convective transport. Using immunohistochemical methods, in both bovine and human eyes, intense staining of albumin was found in the anterior 1/3 of the corneal stroma. There was a gradual reduction in staining intensity from the limbus to the central cornea in the anterior corneal stroma. Less staining was found in the posterior 2/3 of corneal stroma. Additionally, a greater concentration of soluble protein and albumin was found in the anterior stroma than in the posterior stroma of the bovine eyes by biochemical analyses. The theoretical model demonstrated that this distribution of protein required a difference in excluded volume fraction between the anterior and posterior stroma and was consistent with a convective flux originating at the limbus and passing through the corneal stroma. The soluble proteins of the bovine and human cornea are preferentially concentrated in the anterior cornea and near the limbus. This distribution is likely due to differences in excluded volume fraction between the anterior and posterior stroma and a small convective flux passing through the cornea.

Albumins↗
PubMed1997

Effects of anatomic variability on blood flow and pressure gradients in the pulmonary capillaries.

A theoretical model is developed to simulate the flow of blood through the capillary network in a single alveolar septum. The objective is to study the influence of random variability in capillary dimension and compliance on flow patterns and pressures within the network. The capillary bed is represented as an interconnected rectangular grid of capillary segments and junctions; blood flow is produced by applying a pressure gradient across the network. Preferred flow channels are shown to be a natural consequence of random anatomic variability, the effect of which is accentuated at low transcapillary pressures. The distribution of pressure drops across single capillary segments widens with increasing network variability and decreasing capillary transmural pressure. Blockage of one capillary segment causes the pressure drop across that segment to increase by 60%, but the increase falls to < 10% at a distance of three segments. The factors that cause nonuniform capillary blood flow through the capillary network are discussed.

Blood Pressure↗
PubMed1997

On the mechanism of mucosal folding in normal and asthmatic airways.

Previous studies have demonstrated that the airway wall in asthma and chronic obstructive pulmonary disease is markedly thickened. It has also been observed that when the smooth muscle constricts the mucosa buckles, forming folds that penetrate into the airway lumen. This folding pattern may influence the amount of luminal obstruction associated with smooth muscle activation. A finite-element analysis of a two-layer composite model for an airway is used to investigate the factors that determine the mucosal folding pattern and how it is altered as a result of changes in the thickness or stiffness of the different layers that comprise the airway wall. Results demonstrate that the most critical physical characteristic is the thickness of the thin inner layer of the model. Thickening of this inner layer likely is represented by the enhanced subepithelial collagen deposition seen in asthma. Other findings show a high shear stress at or near the epithelial layer, which may explain the pronounced epithelial sloughing that occurs in asthma, and steep gradients in pressure that could cause significant shifts of liquid between wall compartments or between the wall and luminal or vascular spaces.

Asthma↗
PubMed1996

Acute histamine-induced flux of airway liquid: role of neuropeptides.

The role of capsaicin-sensitive neuropeptides in the accumulation of airway wall liquid observed 30 s after histamine infusion was investigated in guinea pigs. Two groups were studied: normal animals and animals in which endogenous neuropeptides had been depleted by capsaicin pretreatment. A rapid intravenous infusion of saline or histamine (11 micrograms/kg resulted in marked but similar changes in pulmonary mechanics in normal and capsaicin-pretreated animals. To assess liquid accumulation in airway wall compartments, the lungs were frozen 30 s after histamine infusion; airways from these lungs, 0.15-2.44 mm in internal perimeter, were imaged by low-temperature scanning electron microscopy. There was no difference in average airway surface liquid thickness (hASL) in normal or capsaicin-pretreated airways in response to saline. In capsaicin-pretreated animals, histamine infusion was associated with a significantly decreased hASL (hASL, cap11/hASL,cap0 = 0.58, P < 0.04). Capsaicin pretreatment, without histamine exposure, caused significant increases in epithelial and submucosal areas (Aepi,cap0/Aepi,norm0 = 1.23, P < 0.06; Asub,cap0/Asub,norm0 = 1.40, P < 0.01). The notation cap0 and cap11 indicates capsaicin-pretreated airways given 0 or 11 micrograms/kg histamine, respectively; similarly, norm0 and norm11 indicate normal airways given 0 and 11 micrograms/kg histamine, respectively. Histamine infusion in capsaicin-pretreated animals was associated with liquid shifts from epithelium to lamina propria and from submucosa to adventitia; however, the total wall area was similar to, if not smaller than, that in capsaicin-pretreated animals without histamine treatment. In contrast, histamine infusion in normal animals resulted in significant increases in the areas of the epithelial and lamina propria compartments (Aepi,norm11/Aepi,norm0 = 1.25, P < 0.05; Alp,norm11/Alp,norm0 = 2.19, P < 0.001) as well as a substantial increase in adventitial area, which was significantly attenuated by capsaicin pretreatment (Aadv,cap11/Aadv,norm11 = 0.40, P < 0.001). The resulting total wall area was more than twice that in normal animals without histamine treatment. Our data indicate that histamine-induced accumulation of liquid in the epithelium, lamina propria, and adventitia of normal airways is rapid in onset, most likely derives from a leaky bronchial microvasculature, and is mediated by the secondary release of neurokinins.

Airway Resistance↗
PubMed1996

Airway closure and reopening assessed by the alveolar capsule oscillation technique.

An alveolar capsule oscillation technique was used to determine 1) the lobe pressure and volume at which airways close and reopen, 2) the effect of expiration rate on closing volume and pressure, 3) the phase in the breathing cycle at which airway closure occurs, and 4) the site of airway closure. Experiments were conducted in excised dog lobes; closure was detected by an abrupt increase in the input impedance of surfacemounted alveolar capsules. Mean transpulmonary pressure (Ptp) at closure was slightly less than zero (Ptp = -2.3 cmH2O); the corresponding mean reopening pressure was Ptp = 14 cmH2O. The expiration rate varied between 1 and 20% of total lobe capacity per second and had no consistent effect on the closing volume and pressure. When lung volume was cycled up to frequencies of 0.2 Hz, closure generally occurred on expiration rather than inspiration. These observations support the conclusion that mechanical collapse, rather than meniscus formation, is the most likely mechanism producing airway closure in normal excised dog lungs. Analysis of measured acoustic impedances and reopening pressures suggests that closure occurs in the most peripheral airways. Reopening during inspiration was often observed to consist of a series of stepwise decreases in capsule impedance, indicating a sequence of opening events.

Airway Resistance↗
PubMed1995

Airway wall liquid. Sources and role as an amplifier of bronchoconstriction.

Airway liquid balance in asthma is largely determined by active plasma exudation from tracheobronchial microvessels into the interstitial spaces of the mucosa, submucosa, and/or adventitia, and from there into the luminal space. This exuded plasma is rich in proteins and cell mediators capable of initiating several events, including activation of sensory neural pathways, plasma protein cleavage, inflammatory cell recruitment, and inhibition of surfactant function. It can act to amplify the bronchoconstrictor response by increasing mucosal and/or submucosal thickness, altering mechanical properties of airway wall compartments, decoupling the airway wall from parenchymal attachments, filling airway interstices, and by creating an additional inward force because of surface tension, resulting in further airway constriction and possibly closure and thereby significantly increasing airways resistance.

Animals↗
PubMed1995

Shear-augmented dispersion in the respiratory system.

Biological systems contain numerous examples of shear-augmented dispersion in which gradients in the velocity profile act in concert with lateral mixing or molecular diffusion to cause materials to disperse at an enhanced rate. Some of the better known examples are found in the respiratory or cardiovascular systems, but other applications include the dispersal of pollutants discharged into a flowing stream, the mixing of contaminants in groundwater flows and the possibility of enhanced transport rates through tissues subjected to transient loads. This review focuses on two examples in the respiratory system, bolus dispersion and high-frequency ventilation, that draw upon a broad range of fundamental studies in shear-augmented dispersion. Simple examples are considered which contain specific features of the considerably more complex real situations. These features include, for example, the effects of turbulence, secondary flows, absorption by the walls, aerosol deposition, complex geometries and oscillatory flow. A scaling analysis is presented that yields the approximate dependence of effective diffusivities associated with shear-augmented dispersion when more detailed analyses are either not warranted or too complex to be tractable.

Animals↗