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C F Dewey

Publications and source records attributed to C F Dewey.

29 records · Page 2Linked to original sources
PubMed1992

Fluid shear stress modulates cytosolic free calcium in vascular endothelial cells.

Cytosolic free Ca2+ concentration ([Ca2+]i) was monitored in single and groups of fura-2-loaded bovine aortic endothelial cells (BAEC) during exposure to laminar fluid shear stress. Application of a step increase in shear stress from 0.08 to 8 dyn/cm2 to confluent BAEC monolayers resulted in a transient increase in [Ca2+]i, which attained a peak value in 15-40 s, followed by a decline to baseline within 40-80 s. The magnitude of the [Ca2+]i responses increased with applied shear stress over the range of 0.2-4 dyn/cm2 and reached a maximum at greater than 4 dyn/cm2. Transient oscillations in [Ca2+]i with gradually diminishing amplitude were observed in individual cells subjected to continuous high shear stress. Elimination of extracellular Ca2+ with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, blockade of Ca2+ entry with lanthanum, depolarization of the cell membrane with high K+, and preconditioning of BAEC in steady laminar flow had little effect on the [Ca2+]i response. In the presence of ATP or ADP, application of shear stress caused repetitive oscillations in [Ca2+]i in single BAEC, whose frequency was dependent on both agonist concentration and the magnitude of applied shear stress. However, apyrase, an ATPase and ADPase, did not inhibit the shear-induced [Ca2+]i responses in standard medium (no added ATP or ADP), suggesting that the shear-induced [Ca2+]i response is not due to ATP released by endothelial cells.

Adenosine Triphosphate↗
PubMed1992

Vascular endothelium responds to fluid shear stress gradients.

In vitro investigations of the responses of vascular endothelium to fluid shear stress have typically been conducted under conditions where the time-mean shear stress is uniform. In contrast, the in vitro experiments reported here have re-created the large gradients in surface fluid shear stress found near arterial branches in vivo; specifically, we have produced a disturbed-flow region that includes both flow separation and reattachment. Near reattachment regions, shear stress is small but its gradient is large. Cells migrate away from this region, predominantly in the downstream direction. Those that remain divide at a rate that is high compared with that of cells subjected to uniform shear. We speculate that large shear stress gradients can induce morphological and functional changes in the endothelium in regions of disturbed flow in vivo and thus may contribute to the formation of atherosclerotic lesions.

Animals↗
PubMed1986

Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro.

The effects of hemodynamic forces upon vascular endothelial cell turnover were studied by exposing contact-inhibited confluent cell monolayers to shear stresses of varying amplitude in either laminar or turbulent flow. Laminar shear stresses (range, 8-15 dynes/cm2; 24 hr) induced cell alignment in the direction of flow without initiating the cell cycle. In contrast, turbulent shear stresses as low as 1.5 dynes/cm2 for as short a period as 3 hr stimulated substantial endothelial DNA synthesis in the absence of cell alignment, discernible cell retraction, or cell loss. The results of these in vitro experiments suggest that in atherosclerotic lesion-prone regions of the vascular system, unsteady blood flow characteristics, rather than the magnitude of wall shear stress per se, may be the major determinant of hemodynamically induced endothelial cell turnover.

Animals↗
PubMed1984

Effects of fluid flow on living vascular cells.

Shear stress produced by a flowing fluid has been found to cause changes in the structure and function of vascular endothelial cells. They tend to become elongated and aligned with the direction of flow. They respond to changes in fluid shear stress (either from low shear to high shear or vice versa) by transiently increasing fluid-phase endocytosis. And they are capable of producing intracellular actin and myosin filaments that are oriented in the flow direction.

Actinin↗
PubMed1984

Influence of hemodynamic forces on vascular endothelial function. In vitro studies of shear stress and pinocytosis in bovine aortic cells.

The relationships between fluid shear stress, a physiologically relevant mechanical force in the circulatory system, and pinocytosis (fluid-phase endocytosis) were investigated in cultured bovine aortic endothelial cells using a specially designed apparatus. Continuous exposure to steady shear stresses (1-15 dyn/cm2) in laminar flow stimulated time- and amplitude-dependent increases in pinocytotic rate which returned to control levels after several hours. After 48 h continuous exposure to steady shear stress, removal to static conditions also resulted in a transient increase in pinocytotic rate, suggesting that temporal fluctuations in shear stress may influence endothelial cell function. Endothelial pinocytotic rates remained constant during exposure to rapidly oscillating shear stress at near physiological frequency (1 Hz) in laminar flow. In contrast, however, a sustained elevation of pinocytotic rate occurred when cells were subjected to fluctuations in shear stress amplitude (3-13 dyn/cm2) of longer cycle time (15 min), suggesting that changes in blood flow of slower periodicity may influence pinocytotic vesicle formation. As determined by [3H]thymidine autoradiography, neither steady nor oscillating shear stress stimulated the proliferation of confluent endothelial cells. These observations indicate that: (a) alterations in fluid shear stress can significantly influence the rate of formation of pinocytotic vesicles in vascular endothelial cells, (b) this process is force- and time-dependent and shows accommodation, (c) certain patterns of fluctuation in shear stress result in sustained elevation of pinocytotic rate, and (d) shear stresses can modulate endothelial pinocytosis independent of growth stimulation. These findings are relevant to (i) transendothelial transport and the metabolism of macromolecules in normal endothelium and (ii) the role of hemodynamic factors in the localization of atherosclerotic lesions in vivo.

Animals↗
PubMed1984

Orientation of endothelial cells in shear fields in vitro.

Vascular endothelial cells subjected to fluid shear stress change their shape from polygonal to ellipsoidal and become uniformly oriented with the flow. In order to study the mechanisms of this response, we have measured the relaxation of bovine aortic endothelial cells that were grown on glass coverslips and exposed to fluid shear stress for 72 hours. An image analysis system was developed to quantify the cell shape relaxation that occurs following the cessation of shear stress. This method provides two different quantitative measures of relaxation: the loss of elongated shape by the cells and the change in cell direction with time. After equilibration to a fluid shear stress level of 8 dynes/cm2, cells immersed in static medium relax their shape in about 20 hours. After 72 hours in this static condition, the cell elongation is comparable to that of unstressed control cells but vestiges remain of the original orientation in the flow direction. This relaxation process contributes to our understanding of the response of vascular endothelium to fluid shear stress.

Animals↗
PubMed1981

The dynamic response of vascular endothelial cells to fluid shear stress.

We have developed an in-vitro system for studying the dynamic response of vascular endothelial cells to controlled levels of fluid shear stress. Cultured monolayers of bovine aortic endothelial cells are placed in a cone-plate apparatus that produces a uniform fluid shear stress on replicate samples. Subconfluent endothelial cultures continuously exposed to 1-5 dynes/cm2 shear proliferate at a rate comparable to that of static cultures and reach the same saturation density (congruent to 1.0-1.5 X 10(5) cells/cm2). When exposed to a laminar shear stress of 5-10 dynes/cm2, confluent monolayers undergo a time-dependent change in cell shape from polygonal to ellipsoidal and become uniformly oriented with flow. Regeneration of linear "wounds" in confluent monolayer appears to be influenced by the direction of the applied force. Preliminary studies indicate that certain endothelial cell functions, including fluid endocytosis, cytoskeletal assembly and nonthrombogenic surface properties, also are sensitive to shear stress. These observations suggest that fluid mechanical forces can directly influence endothelial cell structure and function. Modulation of endothelial behavior by fluid shear stresses may be relevant to normal vessel wall physiology, as well as the pathogenesis of vascular diseases, such as atherosclerosis.

Animals↗
PubMed1979

Boundary layer separation in models of side-to-end arterial anastomoses.

We performed an investigation of boundary layer separation in models of side-to-end anastomoses, used clinically in axillofemoral and femorofemoral grafting. Boundary layer separation occurs when momentum causes a fluid to flow against a local pressure gradient. Models of side-to-end anastomoses were constructed from Dacron grafting material and from clear plastic blocks and tubing. Fluid energy loss across the anastomosis was small and physiologically insignificant. Local adverse pressure gradients were demonstrated near the anastomosis. Flow visualization studies demonstrated characteristic areas of boundary layer separation in the region of the adverse pressure gradients. The separation region involved both the main limb and the side arm. The separation forms a shell or ring of slow-moving fluid around the mainstream. Preliminary studies with pulsatile flow and with blood demonstrate that boundary layer separation occurs under clinical flow conditions. Boundary layer separation may play a role in the development of anastomotic hyperplasia and atherosclerotic deposits in the vicinity of surgical anastomoses.

Arteriosclerosis↗
PubMed1975

Evaluation of carotid stenosis by phonoangiography.

Quantitative spectral (frequency) analyses were performed on 60 carotid bruits in 48 patients with suspected carotid stenosis. The technic was totally noninvasive. Bruits were recorded at the skin surface, analyzed by a minicomputer, and the degree of arterial stenosis estimated using a recently derived theory of sound production by turbulent blood flow. This method has been named phonoangiography. Fifty of the 60 bruits (83 per cent) had spectrums characteristic of turbulent blood flow, and a residual lumen diameter could be calculated. Results from the noninvasvie technic compared well with data obtained from radiographic carotid arteriograms in the 50 bruits with internal carotid artery stenosis. The residual lumen diameter estimated from phonoangiography differed from the radiographic value by less than 1 mm in 83 per cent and less than 1.5 mm in 92 per cent of the studies. Phonoangiography appears to be a useful method for assessment of carotid artery stenosis.

Arteriosclerosis↗
PubMed1970

Phonoangiography: a new noninvasive diagnostic method for studying arterial disease.

Phonoangiography, the quantitative analysis of sounds produced by blood flow, has been used to investigate local fluid motion in arteries narrowed by atherosclerosis. The sound spectra measured in vivo were found to be identical to those obtained in laboratory investigations of turbulent pipe flow. A theoretical model is proposed which: (a) quantitatively relates the in vivo and in vitro data, and (b) allows estimation of the clinically important parameters of arterial diameter, flow velocity, local turbulence intensity, and wall pressure fluctuations. The results of calculations using data from human subjects agree with known arterial diameters and blood flow velocities.

Arteriosclerosis↗