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Biomedical subjects

R M Nerem

Publications and source records attributed to R M Nerem.

At least 91 records · Page 5Linked to original sources
PubMed1980

Assessment of wall shear stress in arteries, applied to the coronary circulation.

Time dependent wall shear rates cannot be directly or accurately measured in arteries using presently available techniques. Here a simple method is presented for calculating them from a single measured velocity waveform (either centreline or cross-sectionally averaged velocity). The method involves only Fourier analysis and the application of given formulae, and it is expected to be approximately valid in any segment of artery which has no branches or sharp curves for a distance of several diameters. It is shown, however, that a frequency response of 30 Hz is required in the velocity measuring device if the resulting wall shear rate waveform is to be accurate throughout the cycle although 10 Hz is adequate if only the rms value is desired. This restriction on accuracy applies to this or any other method of estimating time-dependent wall shear. The method is applied to a prediction of wall shear in the left coronary arteries of the horse, based on measured velocities where they are available and calculated ones where they are not; the results show that in vivo the amplitude of wall shear fluctuations is much greater than the mean. The method is also applied to a scaled down model of the horse coronaries, thought to be representative of man; here the unsteadiness is still important but no longer dominant. The variation of wall shear with distance along the artery is discussed in the context of atherogenesis.

Animals↗
PubMed1979

Vascular casting. A new method for the study of the arterial endothelium.

Vascular casts of the rat aorta were made using modified Batson's No. 17 anatomical corrosion compound. The outline of the silver-stained endothelial cell boundaries were clearly visible on the cast when examined using both scanning electron and light microscopy. The physical properties of the injectate were determined. The exothermic nature of the polymerization of the injectate did not grossly damage the endothelial cells. A method was developed for recovery, without damage, of the arterial tissue surrounding the cast. The technique of vascular casting appears to be a powerful tool for the study of the arterial endothelium which avoids shrinkage artifacts and maintains 3-dimensional geometry.

Animals↗
PubMed1979

Coronary artery pressure development and wave transmission characteristics in the horse.

Measurements of the pressure waveform development and the wave transmission characteristics in the left extramural coronary arteries of the horse have been carried out. Near the ostium the left coronary pressure waveforms are seen to be virtually identical to the corresponding aortic root waveforms; however, the present of low frequency, relatively large amplitude pressure oscillations (on the order of 5 to 10 Hz) gradually become the dominant diastolic feature as one proceeds distally from the left ostium, and these eventually completely mask the incisura. In a limited number of experiments, these oscillations have been simultaneously observed on both centerline velocity and phasic flow signals. These are felt to be primarily due to wave reflection phenomena, but may represent a combined effect of wave reflections and the natural oscillatory motion of the heart mass. Peak systolic pressures were found to remain relatively unchanged as one proceeds distally; however, the end-diastolic pressures were found to decrease steadily, thus giving rise to an increasing pulse pressure and a gradually decreasing mean pressure. Wave speeds in the coronary arteries were found to range between 4 and 11 m.s-1, and the data obtained indicate the wave speed to be highly dependent on both local intralumenal pressure and spatial location.

Animals↗
PubMed1977

The role of multiple noncritical arterial stenoses in the pathogenesis of ischemia.

The hemodynamic effects of multiple noncritical lesions in series were studied in in vitro experiments and in 15 animals. Flow visualization studies were also carried out to obtain insight into the flow pattern in the region of stenosis. Symmetrical stenosis pieces with a 50 per cent reduction in area were placed inside a plexiglass tube and used for both in vitro and in vivo experiments. Varying the number of stenoses and the spacing between them enabled us to study twelve different stenosis configurations during both pulsatile and steady flow. Flow conditions encountered clinically were simulated by varying the average Reynolds number between 30 and 380. Pressure drops across the stenosis test section were measured with a differential pressure transducer and used to calculate critical values for multiple, uniform, noncritical stenoses and for combinations of stenoses of different degrees. Results from steady and pulsatile flow in vitro were comparable, as were those results from the in vivo experiments. The pressure drop across a series of noncritical stenoses was nearly the sum of the individual pressure drops, with only slight dependence upon the spacing between stenoses, Thus it is concluded, from both experimental results and from the theoretical calculations, that the total effect of a series of noncritical stenoses may become critical and produce symptoms of arterial insufficiency.

Animals↗
PubMed1976

Hot film coronary artery velocity measurements in horses.

Coronary velocity measurements have been carried out in anaesthetized, open-chest horses using a constant-temperature, hot-film anemometer system. L-shaped needle probes inserted by direct vessel puncture have been used to measure velocity profiles in the left common, left anterior descending (LAD), and left circumflex coronary arteries. The flow conditions were characterized by peak Reynolds numbers from approximately 200 to 1500 and values of the unsteadiness parameter from 3 to 10. These measurements indicate that in the left common coronary artery the profile is in general skewed towards the outer wall as would be expected for fully viscous flow in a curved tube. In the left anterior descending and left circumflex coronary arteries just distal to the bifurcation, the skewing was found in general to be away from the flow divider. However, in regions of the LAD and left circumflex 5-6 diameters downstream of the bifurcation, the peak systolic and diastolic profiles were indicative of a more fully developed, Poiseuille type flow with only slight skewing observed. The results of this study indicate that the flow in the coronary system, though in general laminar and disturbance free, is extremely varied in character and may exhibit large amplitude, low frequency flow oscillations. Furthermore, for these vessels which all lie on the surface of the myocardium, large systolic flows were observed to be present, even though the major portion of the volume flow was reserved for the diastolic period.

Animals↗
PubMedDate not supplied

An endothelial cell-smooth muscle cell co-culture model for use in the investigation of flow effects on vascular biology.

Flow and the associated shear stress have been shown to play an active role in the regulation of the structure and function of endothelial cells (EC) in vitro. Although cultured EC subjected to flow exhibit an elongated morphology and a decreased cell growth rate rather like those observed in vivo, there are differences in morphology and growth rate, as well as other characteristics, between in vitro and in vivo EC. This suggests that flow is only one of the many factors affecting EC differentiation in vivo. In this study, a co-culture model system was designed, which includes smooth muscle cells (SMC), a matrix of collagen type I, and a confluent monolayer of EC, and this simplified model of the arterial wall was subjected to a steady, laminar shear stress of 10 and 30 dyn/cm2. Under non-flow conditions, EC exhibited an elongated shape, but with a random orientation. In response to flow, there was an alignment with the direction of flow. This alignment occurred more rapidly at 30 dyn/cm2 than at 10 dyn/cm2. The collagen matrix was found to be primordial in the maintenance of a quiescent endothelium, even in the absence of SMC and flow, suggesting the importance of an organized extracellular matrix (ECM) in the differentiation of cells in vivo.

Animals↗
PubMedDate not supplied

Modeling of cryopreservation of engineered tissues with one-dimensional geometry.

Long-term storage of engineered bio-artificial tissues is required to ensure the off-the-shelf availability to clinicians due to their long production cycle. Cryopreservation is likely the choice for long-term preservation. Although the cryopreservation of cells is well established for many cell types, cryopreservation of tissues is far more complicated. Cells at different locations in the tissue could experience very different local environmental changes, i.e., the change of concentration of cryoprotecting chemicals (CPA) and temperature, during the addition/removal of CPA and cooling/warming, which leads to nonuniformity in cell survival in the tissue. This is due to the limitation of mass and heat transfer within the tissue. A specific aim of cryopreservation of tissue is to ensure a maximum recovery of cells and their functionality throughout a tissue. Cells at all locations should be protected adequately by the CPA and frozen at rates conducive to survival. It is hence highly desirable to know the cell transient and final states during cryopreservation within the whole tissue, which can be best studied by mathematical modeling. In this work, a model framework for cryopreservation of one-dimensional artificial tissues is developed on the basis of solving the coupled equations to describe the mass and heat transfer within the tissue and osmotic transport through the cell membrane. Using an artificial pancreas as an example, we carried out a simulation to examine the temperature history, cell volume, solute redistribution, and other state parameters during the freezing of the spherical heterogeneous construct (a single bead). It is found that the parameters affecting the mass transfer of CPA in tissue and through the cell membrane and the freezing rate play dominant roles in affecting the cell volume transient and extracellular ice formation. Thermal conductivity and extracellular ice formation kinetics, on the other hand, have little effect on cell transient and final states, as the heat transfer rate is much faster than mass diffusion. The outcome of such a model study can be used to evaluate the construct design on its survivability during cryopreservation and to select a cryopreservation protocol to achieve maximum cell survival.

Algorithms↗
PubMedDate not supplied

Endothelial cell monolayer formation: effect of substrate and fluid shear stress.

The formation of an endothelial cell (EC) monolayer is one critical factor in the development of a tissue engineered vascular graft. One potential method of endothelialization is the migration of native ECs from the surrounding blood vessel onto the newly implanted graft. In the present study, in vitro experiments were performed to investigate the potential of ECs to migrate on a tissue-engineered blood vessel wall model (TEWM) and form a new monolayer. The TEWM was composed of a three-dimensional, type I collagen matrix seeded with smooth muscle cells. The potential of ECs to form new monolayer was evaluated in the absence and presence of fluid shear stress (10 dynes/cm(2)). The monolayer formation on the TEWM was compared to a control, two-dimensional substrate of glass coated with type I collagen. Results from these studies showed that EC monolayer formation was inhibited on the TEWM in comparison to glass coated with collagen. This correlated with an inhibition of proliferation on the TEWM. The application of shear stress to the EC on the glass coated with collagen also caused an inhibition of monolayer formation, with a corresponding inhibition of proliferation. Furthermore, blocking proliferation by incubation with mitomycin C caused a dose-response inhibition of monolayer formation. In contrast, stimulating proliferation with basic fibro- blast growth factor (bFGF) did not further increase monolayer formation on glass coated with collagen. These results suggest that proliferation is one necessary factor for monolayer formation, although not the only factor, where EC proliferation is regulated by its environment, including both substrate and the local shear stress. Continued investigation into the mechanism and stimulation of EC proliferation on the TEWM may lead to developing new strategies for the endothelialization of a tissue engineered vascular graft.

Cell Adhesion↗
PubMedDate not supplied

Pulsatile and steady flow-induced calcium oscillations in single cultured endothelial cells.

The influence of flow-imposed shear stress on the intracellular calcium concentration ([Ca2+]i) of cultured endothelial cells (ECs) remains incompletely understood. In the present study, we measured [Ca2+]i in single bovine aortic ECs, using fluorescence ratiometric image analysis. The effects of several flow patterns were analysed: steady shear stress (5-70 dyn/cm2), 1-Hz pulsatile shear stress (nonreversing 40 +/- 20 dyn/cm2, reversing 20 +/- 40 dyn/cm2, or purely oscillatory 0 +/- 20 dyn/cm2), or changing shear stress levels. Under all flow conditions, single-cell analyses revealed flow-induced asynchronous [Ca2+]i oscillations, which occurred randomly over the monolayer and which were not seen in the average [Ca2+]i signal corresponding to the monolayer response. The number of single-cell [Ca2+]i oscillations and the corresponding oscillation frequency rose as the shear stress associated with the steady flow increased: 0.06 +/- 0.02 min-1 at 5 dyn/cm2, 0.19 +/- 0.03 min-1 at 20 dyn/cm2, and 0.28 +/- 0.02 min-1 at 70 dyn/cm2 (means +/- SD). Also, the number of oscillations was greater for any type of pulsatile flow (0.53 +/- 0.07 min-1 at 40 +/- 20 dyn/cm2, 0.54 +/- 0.08 min-1 at 20 +/- 40 dyn/cm2, and 0.39 +/- 0.07 min-1 at 0 +/- 20 dyn/cm2), as compared to any level of steady flow. The most dramatic finding was that purely oscillatory flow induced numerous single-cell [Ca2+]i oscillations, yet the average [Ca2+]i response for the monolayer did not change. Furthermore, an EC monolayer switched from low to high (or from high to low) steady flow consistently showed an increase (or a decrease) in the number of single-cell [Ca2+]i oscillations. These experiments show that ECs respond to different flow conditions by varying single-cell [Ca2+]i oscillatory activity. This may have important implications in the endothelium-dependent control of vascular physiology, such as the release of vasoactive substances.

Animals↗