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Biomedical subjects

R D Kamm

Publications and source records attributed to R D Kamm.

At least 19 recordsLinked to original sources
PubMed1992

Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels.

It is likely that factors other than stenosis severity predispose some atherosclerotic plaques to rupture. Because focal increases in circumferential stress may be an important mechanism of plaque rupture, we examined peak circumferential stress of atherosclerotic lesions by using finite element analysis based on idealized two-dimensional cross sections of diseased vessels similar to intravascular ultrasound images. The study was designed to test the hypothesis that subintimal plaque structural features such as thickness of the fibrous cap are more important factors in the distribution of stress in the plaque than stenosis severity. The analysis incorporated equilibrium biomechanical parameters from normal and diseased vessels and determined the stress distribution within the plaque at a mean luminal internal pressure of 110 mm Hg. With a constant luminal area reduction of 70%, maximum circumferential stress (sigma max) normalized to luminal pressure (sigma max/P) increased from 6.0 to 24.8 as the thickness of the lipid pool was increased from 38% to 54% of the plaque thickness because of the thinner fibrous cap over the lipid pool. When the lipid pool thickness was constant, increasing the stenosis severity from 70% to 91% by increasing the fibrous cap thickness decreased sigma max/P from 24.8 to 4.7. When no lipid pool was present and the stenosis severity was increased from 70% to 99%, sigma max/P decreased from 5.3 to 4.7. Thus, reducing the fibrous cap thickness dramatically increases peak circumferential stress in the plaque, whereas increasing the stenosis severity actually decreases peak stress in the plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1992

The source of protein in the aqueous humor of the normal monkey eye.

In vivo aqueous fluorophotometry, morphology, and computational modeling were combined to examine the source of protein and the pathway by which protein enters the aqueous humor of monkeys. A computational model was developed to determine the likelihood of a diffusional route for delivering plasma proteins from ciliary body capillaries via the iris to anterior chamber aqueous humor, bypassing the posterior chamber. Model predictions were compared to aqueous fluorophotometric data obtained from monkeys following a single intravenous injection of fluoresceinated horseradish peroxidase (F-HRP, 250 mg/kg body mass). Model predictions of the magnitude and time course of anterior chamber F-HRP concentration agree with the fluorophotometric measurements. For example, of anterior chamber F-HRP concentration as a percentage of initial plasma F-HRP concentration at 90 min and 180 min post-injection was predicted to be 0.02% and 0.05%, respectively, and was measured to be 0.01-0.03% and 0.03-0.06%, respectively. In addition, model predictions in the case of a constant plasma protein level also are consistent with experimental data. The steady-state anterior chamber total protein concentration as a percentage of plasma protein concentration was predicted to be 0.2% and was assayed to be 0.05-0.2%. As in our previous study of the normal rabbit eye, morphologic and tracer localization evidence combined with the good agreement between model predictions and experimental data lead to the conclusion that a significant amount of the plasma protein normally present in monkey aqueous humor originates in ciliary body capillaries and diffuses anteriorly through the iris and into the anterior chamber.

Animals↗
PubMed1992

Morphologic correlations with fluorophotometric data from monkey eyes with anterior uveitis.

Acute anterior uveitis was induced in monkeys by unilateral intravitreal injection of 1.0 ng of Escherichia coli endotoxin. Twenty-four hours later, each animal received an intravenous injection of 250 mg/kg body weight of fluoresceinated horseradish peroxidase (F-HRP), and fluorophotometric measurements were taken for 90 min. The animals were killed, and both eyes were processed for HRP demonstration. In the anterior chamber aqueous humor of normal control eyes, F-HRP concentrations were less than 0.002 mg/ml at 90 min. The F-HRP concentration was elevated consistently in the endotoxin-injected eyes; however, the magnitude of the effect varied. By fluorophotometry, inflamed eyes fell into two distinct groups. At 90 min, most had an anterior chamber F-HRP concentration of 0.014-0.06 mg/ml, although others had 0.39 mg/ml. In the latter group, an appreciably shorter latency was observed between the time of tracer injection and its detection in the anterior chamber. Aqueous humor protein concentrations, although highest in the most F-HRP-permeable eyes, followed more of a continuum in their distribution and identified less clearly the subpopulations seen by fluorophotometry. Normal eyes had no tracer leakage across either the ciliary epithelial or iris vascular endothelial barriers. All inflamed eyes had HRP leakage across the ciliary epithelium, but the subpopulation of eyes with shorter latencies and higher F-HRP concentrations by fluorophotometry also had iris vascular leakage.

Animals↗
PubMed1992

Modulation of outflow resistance by the pores of the inner wall endothelium.

The juxtacanalicular connective tissue (JCT) is widely believed to generate the bulk of aqueous humor outflow resistance, while the pores of the inner wall endothelium are thought to generate at most 10% of this resistance in humans. However, the hydrodynamic interaction of these two components of the aqueous outflow system, which arises because of their spatial proximity, has only recently been considered. Modelling the JCT as a homogeneously distributed porous material upstream of a low porosity filter (the inner wall endothelium), the pores of the inner wall are found to cause a "funneling effect," in which the aqueous humor flows preferentially through those regions of the JCT nearest the inner wall pores. The bulk of the pressure drop occurs in the immediate proximity of the pores (within three pore radii). This greatly increases the apparent flow resistance of the JCT. For a set of parameters characterizing the normal eye, this enhancement is approximately 30-fold. The conclusion of this study is that changes in inner wall porosity may greatly affect aqueous outflow resistance, despite the low flow resistance of the inner wall pores themselves.

Aqueous Humor↗
PubMed1991

Turbulent pressure fluctuations on surface of model vascular stenoses.

Turbulence frequently develops when blood passes through a stenosis. To study the hypothesis that turbulence near a plaque surface can cause pressure fluctuations that may promote plaque rupture, models of intravascular stenoses were studied. Experimental conditions simulated peak flow in the coronary and carotid arteries through a stenosis of 80 or 90% diameter reduction and into a region where the plaque had widened distally to a 50-75% stenosis. For symmetric stenoses at carotid artery flow rates, peak pressure fluctuations were observed 1-1.5 upstream diameters distal to the stenosis, but there were no significant turbulent pressure fluctuations at coronary artery flow rates. Stenosis asymmetry strongly increased the intensity of turbulent pressure fluctuations at flows simulating carotid flow and resulted in significant pressure fluctuations for coronary flow conditions. Increasing stenosis severity from 80 to 90% increased the root mean square pressure fluctuations 3.6-fold. These studies predict peak to peak pressure fluctuations of 15 mmHg in a 90% asymmetric coronary stenosis; it is possible that turbulence may play a role in acute damage of atherosclerotic plaques, particularly in asymmetric stenoses.

Arterial Occlusive Diseases↗
PubMed1991

Structure-dependent dynamic mechanical behavior of fibrous caps from human atherosclerotic plaques.

BACKGROUND: Although thrombosis associated with a fissured atherosclerotic plaque is believed to be the most common cause of acute coronary syndromes, the underlying factors that trigger plaque rupture are currently unknown. However, the mechanical behavior of the plaque is probably of critical importance. METHODS AND RESULTS: To test the hypothesis that the mechanical properties of a plaque are dependent on its composition and, in particular, that the stiffness of fibrous caps changes within the range of frequencies carried by a physiological pressure wave, the stress-strain relation was studied in 27 fibrous caps and related to the underlying histological structure of the fibrous cap. Fibrous caps were obtained during 14 autopsies from the abdominal aorta and were classified by histological examination as cellular (n = 7), hypocellular (n = 9), or calcified (n = 11). Hypocellular fibrous caps were 1-2 times stiffer than cellular caps (p less than 0.005), and calcified caps were 4-5 times stiffer than cellular caps (p less than 0.005). All 27 fibrous caps demonstrated an increase in stiffness with increasing frequencies of stress ranging from 0.05 to 10 Hz; the increase in stiffness was similar in all three histological classes. CONCLUSIONS: We conclude that the stiffness of fibrous caps from human atherosclerotic plaques is related to the underlying histological structure and that the stiffness increases with frequency in the range of physiological heart rates. The protective benefit of beta-adrenergic receptor blocking agents in coronary artery disease may, in part, be related to the frequency dependence of atherosclerotic plaque stiffness.

Arteriosclerosis↗
PubMed1991

The pressure and volume dependence of the rate of wash-out in the bovine eye.

The rate of increase of outflow facility (the wash-out rate) was measured in bovine eyes at 6 and 15 mm Hg. The time-rate-of-change of facility was less at 6 mm Hg (0.20: delta facility/hour) than at 15 mm Hg (0.44). However, when the data was analyzed as a function of volume passing through the outflow system, the volume-rate-of-change of facility was the same at 6 (0.35: delta facility/ml) and 15 mm Hg (0.34). This was consistent with the hypothesis of macromolecules "washing-out" of the aqueous outflow system, if these macromolecules were saturable in the perfusate.

Animals↗
PubMed1990

The filtration characteristics of the aqueous outflow system.

To determine the filtration characteristics of the aqueous outflow system, microspheres (0.18 micron -1.1 micron) were perfused through enucleated human and bovine eyes. The microspheres were smaller than morphologically determined flow dimensions, and yet a significant fraction of all sizes of microspheres were captured. The bovine (calf) aqueous outflow system was found to be a far more efficient filter than was the human outflow system. Combining the experimental results with morphological observations and theoretical calculations leads to the conclusion that 'sticky wall' interactions are responsible for much of the microsphere capture, and that the site of filtration may be distinct from the site of flow resistance. Consequently, the dimension of the sites generating flow resistance cannot be determined from filtration studies.

Animals↗
PubMed1990

Flow distribution in a single bifurcation during high-frequency oscillation.

The distribution of flow in a single bifurcation was studied to examine what factors played a critical role. Flow was preferentially directed down the straightest pathway when higher frequencies and/or larger tidal volumes were used, but otherwise followed the pattern dictated by the distal impedance regardless of bifurcation geometry. In a symmetrical model, the observed flow distribution was in good agreement with a mathematical prediction based on linear impedance theory, though this was not the case when tidal volumes were increased. The difference in mean pressure between the two terminal units was also a strong function of branching angle and the Reynolds number. These findings suggest that the geometrical factors and local flow conditions contribute to both the flow and mean pressure distribution in an inertia-induced nonlinear manner. Consequently, linear impedance theory can be applied only to the limited situation of low tidal volume and symmetric configuration.

High-Frequency Ventilation↗
PubMed1990

Periodic flow at airway bifurcations. III. Energy dissipation.

We measured the energy dissipation associated with large-amplitude periodic flow through airway bifurcation models. Each model consisted of a single asymmetric bifurcation with a different branching angle and area ratio, with each branch terminated into an identical elastic load. Sinusoidal volumetric oscillations were applied at the parent duct so that the upstream Reynolds number (Re) varied from 30 to 77,000 and the Womersley parameter (alpha) from 4 to 30. Pressures were measured continuously at the parent duct and at both terminals, and instantaneous branch flow rates were calculated. Time-averaged energy dissipation in the bifurcation was computed from an energy budget over a control volume integrated over a cycle and was expressed as a friction factor, F. We found that when tidal volume was small [ratio of tidal volume to resident (dead space) volume, VT/VD less than 1], F was independent of branching angle and fell with increasing alpha and VT/VD. When tidal volume was large (VT/VD greater than 1), F increased with increasing branching angle and varied less strongly with alpha and VT/VD. No simple benchmark flow represented the data well over the entire experimental range. This study demonstrates that only two nondimensional parameters, alpha and VT/VD, are necessary and are sufficient to describe time-averaged energy dissipation in a given bifurcation geometry during sinusoidal flow.

Energy Metabolism↗
PubMed1990

Background-protein effects on fluorophotometric data.

Fluorescent tracers are commonly used in fluorophotometric studies of ocular fluids and tissues that contain background protein. Background-protein concentrations were found to decrease or increase significantly the measure of fluorescence emitted from solutions containing sodium fluorescein, fluorescein-labeled dextran, or fluorescein-labeled horseradish peroxidase. The effect of background protein on fluorescence was expressed as a function of the specific fluorescent tracer, tracer concentration, and background-protein concentration; it can be corrected in the analysis of fluorophotometric data. Fluorophotometric studies--particularly those in which the background-protein level is expected to be abnormally high, such as postoperative and pathologic studies--may need to include either a data correction based on measured effects of background protein on tracer fluorescence or, in the case of clinical investigations, recognize at least the potential for a range of possible interpretations.

Dextrans↗
PubMed1990

The source of proteins in the aqueous humor of the normal rabbit.

Aqueous fluorophotometric, tracer localization and modeling methods were combined to document the existence of a pathway in the normal rabbit for the diffusion of proteins from the ciliary and iridial process stromas through the iris stroma into the aqueous humor of the anterior chamber. A new custom-conjugated tracer, fluoresceinated horseradish peroxidase (F-HRP), was used. Anesthetized rabbits were injected intravenously with F-HRP (250 mg/kg). In some animals, aqueous fluorophotometric and tracer localization studies were performed on the same eyes. Anterior chamber fluorescence was detected 2-10 min post-injection and rose to concentrations of 0.01-0.05 mg/ml 60 min post-injection. Subsequent tracer localization studies of these eyes revealed that the morphologic components of the blood-aqueous barrier were intact, that is, no leakage of F-HRP from the iris vasculature or across the ciliary epithelium was observed. Separate tracer localization studies were performed to examine the time course of the route(s) by which tracer entered the anterior chamber. These studies revealed a "wave" of tracer that migrated from the ciliary and iridial process stromas, through the iris, and arrived at the anterior iris surface approximately 8 min post-injection. A pharmacokinetic model based on the diffusional pathway was developed to describe the time course of the concentration of plasma macromolecules in the ciliary body, iris and anterior chamber. Model predictions were consistent with aqueous fluorophotometric and tracer localization results. The diffusion model can account for a major fraction of protein entering the aqueous humor of normal rabbit eyes.

Animals↗
PubMed1989

Is airway closure caused by a liquid film instability?

A physical model for small airway closure is developed, based on the assumption that closure occurs as a result of a surface tension-induced instability of the thin liquid film lining the airways. To distinguish this mechanism from others involving airway compliance, experiments were performed in rigid tubes, 1 mm in diameter, with length-to-diameter ratios between one and ten. Oil was added to the film in small increments and photographed at each stage. For total liquid volumes (V) less than some critical value (Vc) surface tension draws the oil into an axi-symmetric film on the tube walls leaving the lumen relatively unobstructed. When V exceeds Vc, the film becomes unstable and collapses, bridging the lumen and causing obstruction. The ratio of Vc to the tube diameter cubed was found to be approximately 0.7 for the entire range of tube lengths studied. These experimental findings were then used to predict airway closure in a morphometric model of the bronchial tree. Assuming that the liquid film at TLC is 10 microns and that the volume of each airway varies in direct proportion to lung volume, the model predicts that airway closure will first occur in the terminal bronchioles at a lung volume of 23% TLC, in approximate agreement with observed values of residual volume.

Airway Obstruction↗
PubMed1989

Toward improved methods of high frequency ventilation: a study of gas transport mechanisms.

Prior studies of gas transport mechanisms are reviewed with the aim of using these results to suggest improvements over current methods of ventilation. These concepts are cast in a simpler framework that more clearly identifies those factors that limit the rate of gas transport under conditions typical of HFV. One simplification introduced simulates the enhancement of molecular diffusion due to the movement of gas back-and-forth through regions of varying cross-sectional area. The region of the lung that currently poses the greatest resistance to gas transport is represented by those airways having diameters in the range of 1.0 to 2.5 mm. This suggests that new efforts should be devoted to better understanding the nature of transport in this zone and to the development of variations in the method of ventilation that have the greatest influence there.

High-Frequency Ventilation↗
PubMed1989

Parametric evaluation of forced expiration using a numerical model.

Numerical calculations were performed to study the influence of several physiologic parameters on a forced expiration. It was found that the axial distribution of airway compliance produced profound changes in the detailed flow pattern, as characterized by the axial distributions of speed index and area ratio, but had little effect on the flow-volume curve. Similar results were obtained when the expression for frictional losses was changed to reflect new experimental results. In contrast, changes in airway size and geometry altered both the detailed flow pattern and the mean expiratory flow rate. The shape of the flow-volume curve remained unchanged.

Forced Expiratory Flow Rates↗
PubMed1989

Some features of oscillatory flow in a model bifurcation.

Oscillatory flow in the lung is studied using an order-of-magnitude analysis and flow visualization experiments in a single bifurcation with lung-like geometry. The results are used to obtain a classification scheme that identifies three major flow regimes, distinguished on the basis of whether the flow is dominated by unsteadiness, viscous effects, or the effects of convective acceleration. The unsteady regime is found to exist for values of a dimensionless stroke length (L/a, i.e., stroke volume/local cross-sectional area) less than or equal to 3 and for values of a dimensionless frequency (alpha 2 = alpha 2 omega/nu, where alpha is airway radius, omega the oscillatory frequency, and nu the kinematic viscosity) less than or equal to 10 in basic agreement with previous studies. The viscous regime is found when alpha 2(L/a)(a/R)1/2 less than 10 and alpha 2 less than 10 where R is the local radius of curvature in the bifurcation; the convective regime is found when alpha 2(L/a)(a/R)1/2 greater than 10 and L/a greater than 3. This same approach yields scaling laws for the magnitude of secondary flow velocities and shows that the ratio of secondary-to-axial velocity is small everywhere outside of the convective regime where it scales with (a/R)1/2. Comparison of these results to related simple flows shows that many of the features observed can be attributed to the effects of curvature, suggesting that the influence of the flow divider and of area change may be of lesser importance than previously thought.

In Vitro Techniques↗