Theoretical models for transport of low-density lipoproteins in the arterial wall.
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Biomedical subjects
Publications and source records attributed to C K Colton.
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125I-albumin was injected intravenously into normal conscious rabbits. The rabbits were killed after 10 minutes to 24 hours, and the descending thoracic aorta was excises immediately, opened longitudinally, rinsed, and frozen. Samples of frozen aorta were sectioned paralled to the intimal surface and washed with trichloroacetic acid (TCA) prior to counting. TCA-soluble tissue radioactivity slowly increased with time, suggesting that 125I was cleaved gradually from the labeled albumin within the aortic wall. At up to 4 hours, transmural concentration profiles of TCA-precipitable radioactivity had steep gradients near the intimal surface, moderate gradients near the medial-advential border, and were relatively falt in the middle of the media. After 24 hours, the steep intimal gradient had disappeared. Concentrations were otherwise comparable to those at 4 hours. The rate of accumulation of TCA-precipitable radioactivity was rapid initially (measurable concentrations were found throughout the media after only 10 minutes) and decreased with time. The results are consistent with entry of 125I-albumin into the media from both the luminal and adventitial sides. Approximate calculations indicate that the albumin mass transfer resistance associated with the intimal endothelium is about 1 order of magnitude greater than that associated with the media.
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The collective kinetic behavior of a linear array of cells containing a substrate inhibited enzyme is studied with a model in which each cell is considered a well-stirred compartment surrounded by a semipermeable membrane. At large values of a reaction-permeation modulus, wherein substrate access to interior cells is limited, plots of total reaction rate versus concentration of the external reservoir show sharp projections which correspond to dominant reaction occurring in a pair of symmetrically placed cells. Over prescribed ranges of reservoir concentration, multiple stable steady states can occur, some of which are characterized by asymmetric profiles of concentration and reaction rate across the array. A simple stability criterion is proposed and applied to arrays with arbitrary numbers of cells.
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The transport characteristics of a hollow-fiber blood ultrafilter were studied in vitro to provide an understanding of the factors which control solute removal rate and to permit design of a full-scale clinical device. The dependence of ultrafiltrate flux on transmembrane pressure difference, protein concentration, flow rate, and fiber geometry was correlated in terms of available theoretical analyses. Solute rejection was 1.0 for albumin and decreased to nearly zero for solutes of several thousand molecular weight. An analysis of overall hemodiafilter behavior showed that blood and ultrafiltrate flow rates of 200 ml. per minute can be attained with a device of reasonable size which would provide an inulin whole blood clearance of about 100 ml. per minute.
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Hemodiafiltration, a process in which whole blood is first diluted with a physiologic electrolyte solution and then ultrafiltered across a membrane to convectively remove solutes and excess water, has been applied clinically for the first time. Six-hour hemodiafiltration with a 1.6 m.2 hollow-fiber ultrafilter was applied intermittently to an anephric patient as an alternative to 6-hour hemodialysis using a 1.45 m.2 coli. A quantitative basis for evaluating clinical hemodiafiltration kinetics was developed, and the results were compared with data from prototype devices. With blood, diluting fluid, and ultrafiltrate flow rates of 200 ml. per minute, removal rates of urea and creatinine by both hemodiafiltration and dialysis were comparable, but for solutes of larger molecular weight (uric acid, phosphate, and inulin) removal rate was significantly greater for hemodiafiltration. The observed ultrafiltrate flux was similar to values predicted from in vitro studies. With the present membrane formulation the measured sieving coefficients for inulin, creatinine, and urea were not significantly different from one, and whole blood clearances for these solutes were 117, 108, and 101 ml. per minute, respectively. This solute clearance pattern is very similar to the human kidney and in sharp contrast to standard coil hemodialysis.
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