Search PubMed⌕ Search

Biomedical subjects

J D Humphrey

Publications and source records attributed to J D Humphrey.

At least 37 records · Page 2Linked to original sources
PubMed2003

A constrained mixture model for arterial adaptations to a sustained step change in blood flow.

A sustained change in blood flow results in an arterial adaptation that can be thought to consist of two general steps: an immediate vasoactive response that seeks to return the wall shear stress to its homeostatic value, and a long-term growth and remodeling process that seeks to restore the intramural stresses and, if needed, the wall shear stress toward their homeostatic values. Few papers present mathematical models of arterial growth and remodeling in general, and fewer yet address flow-induced changes. Of these, most prior models build upon the concept of "kinematic growth" proposed by Skalak in the early 1980s (Skalak R (1981) In: Proceedings of the IUTAM Symposium on finite elasticity. Martinus Nijhoff, The Hague, pp 347-355). Such approaches address important consequences of growth and remodeling, but not the fundamental means by which such changes occur. In this paper, therefore, we present a new approach for mathematically modeling arterial adaptations and, in particular, flow-induced alterations. The model is motivated by observations reported in the literature and is based on a locally homogenized, constrained mixture theory. Specifically, we develop a 3-D constitutive relation for stress in terms of the responses of the three primary load-bearing constituents and their time-varying mass fractions, with the latter accounting for the kinetics of the turnover of cells and extracellular matrix in changing, stressed configurations. Of particular importance is the concept that the natural configurations of the individual constituents can evolve separately and that this leads to changes in the overall material properties and empirically inferred residual stress field of the vessel. Potential applications are discussed, but there is a pressing need for new, theoretically motivated data to allow the prescription of specific functional forms of the requisite constitutive relations and the values of the associated material parameters.

Adaptation, Physiological↗
PubMed2003

Further evidence for the dynamic stability of intracranial saccular aneurysms.

It has long been thought that intracranial saccular aneurysms enlarge and rupture because of mechanical instabilities. Recent nonlinear analyses suggest, however, that at least certain sub-classes of aneurysms do not exhibit quasi-static limit point instabilities or dynamic instabilities in response to periodic loading, and consequently, that the natural history of these lesions is likely governed by growth and remodeling processes. In this paper, we present additional results that support the finding that one particular sub-class of saccular aneurysms is dynamically stable. Specifically, we extended recent results of Shah and Humphrey, which are based on the assumption that some saccular aneurysms can be modeled as spherical elastic membranes surrounded by a viscous cerebrospinal fluid, to account for a viscohyperelastic behavior of the aneurysm. It is shown that inclusion of a "short-term" viscoelastic contribution to the mechanical behavior of an aneurysm serves to increase its dynamic stability against various disturbances.

Aneurysm, Ruptured↗
PubMed2003

Altered mechanical behavior of epicardium due to isothermal heating under biaxial isotonic loads.

Recent isothermal biaxial isotonic tests suggest that increasing the temperature hastens the rate of denaturation of epicardium whereas increasing the mechanical load during heating delays this process, findings that are consistent with prior uniaxial tests on tendons. Yet, contrary to uniaxial reports, a clear time-temperature-load equivalency was not found in this multiaxial setting. There is, therefore, a need to delineate multiaxial thermomechanical behavior in greater detail, and ultimately, to correlate changes therein with the underlying microstructure. Toward this end, we describe a new experimental approach for quantifying heating-induced changes in the multiaxial mechanical response of thin sheet-like specimens. Illustrative results are presented for bovine epicardium subjected to nine different thermomechanical loading protocols. Among other results, it is shown that thermal damage tends to increase the stiffness at low strains and that overall changes in extensibility correlate well with the degree of thermal damage independent of the specific thermomechanical protocol. Multiaxial changes in behavior are nevertheless complex, and there is a need for significantly more testing before constitutive relations can be formulated.

Adaptation, Physiological↗
PubMed2003

Effect of thermal damage and biaxial loading on the optical properties of a collagenous tissue.

Thermal denaturation can induce marked changes in the optical and mechanical properties of collagenous tissues. The optical properties are important in both therapeutic and diagnostic applications of lasers in medicine. Although mechanical stress can be caused by collagen shrinkage in laser-based therapies, how the mechanical loading state affects the optical properties is not well understood. We used a new computer-controlled biaxial testing system to subject bovine epicardium to various loading conditions both before and after multiple levels of thermal damage. An integrating sphere technique was used to measure transmittance and diffuse reflectance, from which absorption and scattering coefficients were calculated using a Monte Carlo method. Results showed that the scattering coefficient increased with increasing mechanical load but decreased as the degree of thermal damage increased. There was no significant change in the absorption coefficient due to thermal damage over the ranges studied.

Animals↗
PubMed2002

Denaturation of collagen via heating: an irreversible rate process.

Heating therapies are increasingly used in cardiology, dermatology, gynecology, neurosurgery, oncology, ophthalmology, orthopedics, and urology, among other medical specialties. This widespread use of heating is driven primarily by the availability of new technology, not by a detailed understanding of the biothermomechanics. Without basic quantification of the underlying physical and chemical processes in terms of parameters that can be controlled clinically, identification of preferred interventions will continue to be based primarily on trial and error, thus necessitating large clinical studies and years of accumulative experience. Perusal of the literature reveals that much has been learned over the past century about the response of cells, proteins, and tissues to supra-physiologic temperatures; yet, the associated findings are reported in diverse journals and the underlying basic processes remain unidentified. In this review, we seek to contrast various findings on the kinetics of the thermal denaturation of collagen and to encourage investigators to consider the many open problems in part via a synthesis of results from the diverse literatures.

Collagen Type I↗
PubMed2002

Measurement of finite-strain dependent permeability of biomembranes.

A complete understanding of fluid exchanges in tissues and organs requires knowledge of the permeability of their delimiting membranes as a function of the finite strain that they experience. One reason for the current dearth of data in the literature is the need for new theoretically motivated experimental approaches. In this paper, we use a general scaling to identify non-dimensional parameters that are measured easily by combining a simple pressure-driven diffusion chamber with a method to induce equibiaxial and homogeneous finite strains that can be measured via a non-contacting video system. Illustrative results on excised bovine epicardium reveal a nonlinear relationship between a non-dimensional permeability and finite strain up to stretches of 60%.

Animals↗
PubMed2002

Elastodynamics and arterial wall stress.

Recent advances in molecular and cell biology have emphasized the fundamental importance of mechanical factors in regulating the structure and function of cells and extracellular matrix in the vasculature. Consequently, there is an ever-greater motivation to calculate accurately the stress and strain fields in the arterial wall and how they change with disease, injury, and clinical treatment. Although there is an extensive literature on arterial mechanics, our understanding is still far from complete. In this paper, we review some of the salient findings with regard to wall properties, suggest some possible improvements in the calculation of wall stress, and identify some unresolved problems for further research.

Arteries↗
PubMed2002

Approach to quantify the mechanical behavior of the intact embryonic chick heart.

The heart undergoes remarkable changes during embryonic development due to genetic programing and epigenetic influences such as mechanical loads. An important goal is to develop mathematical models that describe and predict the influence of mechanics on cardiac development, yet the data needed to develop such models remain scant. In particular, prior data from embryonic hearts have come from one-dimensional tests, which reveal well the general characteristic behaviors but are not sufficient for quantifying the complex material behavior exhibited by most soft tissues. We developed a computer-controlled system for quantifying in vitro the multiaxial, regionally dependent mechanical response of the intact embryonic chick heart to controlled distension pressures; such tests have not been accomplished heretofore but promise to contribute to our understanding for they better mimic the native loading conditions and geometry. Calibration of the device indicated that distending the hearts using low flow rates avoids significant viscous losses and thereby allows pressure to be measured directly over small ranges (0-2 mmHg) with good resolution (0.01 mm Hg). Likewise, an on-line video system allows two-dimensional strains to be measured regionally by tracking the motions of triplets of closely spaced (100 microm) microspheres to reasonable resolution (2.5 microm/pixel). Illustrative data from 18 hearts show the utility of the new system, confirm previous findings with regard to the strong viscoelastic response of the stage 18 embryonic chick heart, and provide guidance for the design of future experiments.

Animals↗
PubMed2002

Effects of aging on vasoconstrictor and mechanical properties of rat skeletal muscle arterioles.

Exercise capacity and skeletal muscle blood flow during exercise are reduced with advancing age. This reduction in blood flow capacity may be related to increased reactivity of skeletal muscle resistance vessels to vasoconstrictor stimuli. The purpose of this study was to test the hypothesis that aging results in increased vasoconstrictor responses of skeletal muscle resistance arterioles. First-order (1A) arterioles (90-220 microm) from the gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-344 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasoconstriction in response to increases in norepinephrine (NE; 1 x 10(-9)-1 x 10(-4) M) and KCl (20-100 mM) concentrations and increases in intraluminal pressure (10-130 cmH(2)O) were evaluated in the absence of flow. Responses to NE and KCl were similar in both soleus and gastrocnemius muscle arterioles from young and aged rats. In contrast, active myogenic responses to changes in intraluminal pressure were diminished in soleus and gastrocnemius arterioles from aged rats. To assess whether alterations in the mechanical properties of resistance arterioles underlie altered myogenic responsiveness, passive diameter responses to pressure and mechanical stiffness were evaluated. There was no effect of age on the structural behavior (passive pressure-diameter relationship) or stiffness of arterioles from either the soleus or gastrocnemius muscles. These results suggest that aging does not result in a nonspecific decrease in vasoconstrictor responsiveness of skeletal muscle arterioles. Rather, aging-induced adaptations of vasoreactivity of resistance arterioles appear to be limited to mechanisms that are uniquely involved in the signaling of the myogenic response.

Aging↗
PubMed2001

Compressive stress-relaxation of human atherosclerotic plaque.

Knowledge of the mechanical properties of human atherosclerotic plaque is fundamental to understanding atherosclerosis and its treatment. Data are scant, however, particularly with respect to the time-dependent nature of plaque behavior. Previous experiments in our lab showed that human plaques do not exhibit the traditional preconditioning behavior common to most soft tissues. In particular, the behaviors of three classes of plaques differed fundamentally in response to multiple, successive, cyclic compression protocols. In this report, we demonstrate that plaques exhibit different responses to successive relaxation tests in uniaxial compression. Not only is there significant relaxation, but there are composition-dependent differences in the general character of the relaxation responses. Such information on the time-dependent behavior is important for the design of clinical protocols such as stenting or angioplasty wherein the atherosclerotic vessel is subjected to persistent or multiple short duration loadings. This study presents a step toward a better understanding of the biomechanical behavior of atherosclerotic plaques; however, the need for much more data remains.

Angioplasty↗
PubMed2001

On the potentially protective role of contact constraints on saccular aneurysms.

Most intracranial saccular aneurysms remain asymptomatic until rupture. Yet, some unruptured lesions present with various symptoms, often related to the compression of a nerve or other intracranial tissue. An obvious question, therefore, is whether or not symptomatic unruptured lesions necessarily have a greater rupture-potential than asymptomatic ones. In this paper, we show numerically that contact constraints can have a protective effect on certain lesions. Specifically, finite element analyses of stress fields in model axisymmetric lesions, with and without the presence of a rigid contacting obstacle at the fundus, reveal that with the exception of near point loads, the constraint decreases the stresses near the fundus. Given that it is well accepted that rupture occurs when wall stress exceeds wall strength, these findings suggest that the rupture-potential will be lower in at least one sub-class of constrained versus comparable unconstrained lesions. Because of the myriad of sizes, shapes, and compositions of saccular aneurysms, however, there is a need to examine this important issue further, hopefully based on an increased awareness for clinical data on lesion-tissue interactions.

Aneurysm, Ruptured↗
PubMed2001

Stress, strain, and mechanotransduction in cells.

It is widely accepted that numerous cell types respond to mechanical stimuli, yet there is no general agreement as to whether particular cells respond directly to stress, strain, strain-rate, strain-energy, or other mechanical quantities. By recalling the definitions of the mathematical (not physical) concepts of stress and strain, it is suggested herein that cells cannot respond directly to these continuum metrics or to quantities derived from them--mechanistic models will need to be based on more fundamental quantities, as, for example, inter-atomic forces or conformational changes of the appropriate molecules. Nonetheless, the concepts of stress and strain should continue to play an important role in mechanobiology, both in the identification of empirical correlations and in the development of phenomenological constitutive models, each of which can contribute to our basic understanding as well as help in the design of future experiments and some clinical interventions. It is important to remember, therefore, that empirical correlations and most constitutive relations in continuum mechanics do not seek to model the actual physics--rather, their utility is in their predictive capability, which is often achieved via different relations in terms of different metrics for the same material under different conditions. Hence, with regard to quantifying cellular responses to mechanical stimuli, we must delineate between the identification of fundamental mechanisms and the formulation of phenomenological correlations, the latter of which only requires convenient metrics that need not be unique or physical.

Biomechanical Phenomena↗
PubMed2001

Stress-modulated growth, residual stress, and vascular heterogeneity.

A simple phenomenological model is used to study interrelations between material properties, growth-induced residual stresses, and opening angles in arteries. The artery is assumed to be a thick-walled tube composed of an orthotropic pseudoelastic material. In addition, the normal mature vessel is assumed to have uniform circumferential wall stress, which is achieved here via a mechanical growth law. Residual stresses are computed for three configurations: the unloaded intact artery, the artery after a single transmural cut, and the inner and outer rings of the artery created by combined radial and circumferential cuts. The results show that the magnitudes of the opening angles depend strongly on the heterogeneity of the material properties of the vessel wall and that multiple radial and circumferential cuts may be needed to relieve all residual stress. In addition, comparing computed opening angles with published experimental data for the bovine carotid artery suggests that the material properties change continuously across the vessel wall and that stress, not strain, correlates well with growth in arteries.

Animals↗
PubMed2000

Surveillance for aquabirnavirus in fish hatcheries in Victoria.

OBJECTIVE: To determine whether or not aquabirnavirus is present in Victorian fish hatcheries. PROCEDURE: Milt and ovarian fluids were collected from brood stock at 12 hatcheries and cultured in two sensitive cell lines for the presence of viruses. RESULTS: No cytopathic effect was detected indicating the absence of virus. CONCLUSION: There is no evidence of infection with aquabirnavirus or Epizootic Haematopoietic Necrosis virus in Victorian fish hatcheries.

Animals↗
PubMed2000

Effects of heat-induced damage on the radial component of thermal diffusivity of bovine aorta.

The extent of the change in thermal diffusivity of soft tissues due to heat-induced damage is not well known. Reported here are the results of using the flash method to measure the through-the-wall component of thermal diffusivity of bovine aorta before and after the tissue has undergone two hours of heating at 75 degrees C. The measurements indicate a 10.1 percent increase in the thermal diffusivity of the tissue post-heating. While this change may not result in a significant change in the tissue temperature profile, further study is needed to quantify the thermal diffusivity in other coordinate directions, as well as the mechanisms by which this change in properties occurs.

Animals↗
PubMed1999

Finite strain elastodynamics of intracranial saccular aneurysms.

Various investigators suggest that intracranial saccular aneurysms are dynamically unstable, that they resonate in response to pulsatile blood flow. This hypothesis is based on linearized analyses or experiments on rubber "models", however, and there is a need for a more critical examination. Toward this end, we (a) derive a new nonlinear equation of motion for a pulsating spherical aneurysm that is surrounded by cerebral spinal fluid and whose behavior is described by a Fung-type pseudostrain-energy function that fits data on human lesions, and (b) use methods of nonlinear dynamics to examine the stability of such lesions against perturbations to both in vivo and in vitro conditions. The numerical results suggest that this sub-class of lesions is dynamically stable. Moreover, with the exception of transients associated with initial perturbations, inertial effects appear to be insignificant for fundamental forcing frequencies less than 10 Hz and hence for typical physiologic and laboratory conditions. We submit, therefore, that further study of the mechanics of saccular aneurysms should be focused on quasi-static stress analyses that investigate the roles of lesion geometry and material properties, including growth and remodeling.

Algorithms↗
PubMed1999

Mechanical behavior of a vein pouch saccular aneurysm model.

The response of an intracranial saccular aneurysm to applied loads, whether blood pressure or endovascular intervention, depends on both the geometry and material properties of the lesion. Yet, in the development of animal models of these lesions little attention has been given to the evaluation of their mechanical behavior. Our goal was to compare the multiaxial mechanical behavior of a canine vein pouch model to published data on veins and human aneurysms. Nine vein pouches were created surgically in six mongrel dogs by anastomosing a 2 cm segment of the external jugular vein to the common carotid artery in an end-to-side fashion. The lesions were harvested one week post-surgery and subjected to cyclic inflation tests using a custom system. Pressure-regional strain data revealed that vein pouch aneurysms are very extensible for pressures up to 30 mmHg, especially in the axial direction, but stiff thereafter. None of the lesions ruptured in vivo or during inflation tests. Based on these data, we conclude that the overall behavior of canine vein pouch lesions, at one week post-surgery, did not mimic well that of human aneurysms. Thus, there is a need to pursue modifications or other models for the purposes of clinically relevant studies of lesion growth, rupture, and treatment.

Animals↗