Biomedical subjects
Publications and source records attributed to P L Blackshear.
This article describes three different types of extracorporeal blood pumps and the physiology of blood flow and analyzes the circulatory changes introduced by the pumping during heart-lung bypass. Associated clinical problems are briefly discussed.
A new method is presented to describe the low shear rate behavior of blood. We observed the response of a thin layer of sedimenting blood to a graded shear stress in a wedge-shaped chamber. The method allows quantitation of the degree of phase separation between red cells and plasma, and extracts the yield stress of the cell phase as a function of hematocrit. Our studies showed that the behavior of normal human blood underwent a transition from a solid-like gel to a Casson fluid. This transition began at the Casson predicted yield stress. The viscoelastic properties of blood were examined at shear stresses below the yield stress. The measured Young's elastic moduli were in good agreement with published data. The yield stress of blood showed a linear dependence on hematocrit up to 60%, and increased more rapidly at higher hematocrit.
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Previous investigations have shown that incubation of human erythrocytes with the ionophore A23187 and calcium causes accumulation of the cation, losses in potassium, water, and cellular volume, hydrolysis of adenosine triphosphate (ATP), conversion of biconcave discocytes to echinocytes and spheroechinocytes, and marked increases in erythrocyte resistance to micropipette aspiration. Subsequent studies demonstrated that prevention of water and potassium loss blocked the influence of calcium loading on erythrocyte stiffness without affecting calcium uptake by the cells or hydrolysis of ATP. In the present study erythrocytes were exposed to conditions that permitted individual or coordinate manipulation of cellular ATP, water, potassium, and calcium in order to determine which factors developing as a result of calcium loading were responsible for the calcium-induced changes in erythrocyte viscoelastic properties. Results of the study demonstrate that volume loss, ATP hydrolysis, and potassium depletion do not individually or in combination cause increases in erythrocyte stiffness. However, all of these changes are essential and must develop in conjunction with calcium loading in order for erythrocytes to develop diminished deformability and elasticity.
Pressure-driven fluid flow across the arterial wall was measured to determine wall hydraulic conductivity (Lp) before and after removal of the endothelium. The thoracic aortas of rabbits, anesthetized with Nembutal, were cannulated, perfused with oxygenated Ringer solution, and removed. With one cannula connected to a capillary manometer and the other closed, the manometer meniscus shift could be used as an indication of fluid loss through the wall plus vessel volume increase (creep). The latter effect, when measured, accounted for about one-fourth of the total volume displacement. The Lp given in cm/(s.cmH2O) +/- SD, was 3.30 +/- 0.96 x 10(-8). Another method employed continuous weighing of a closed aortic segment to obtain fluid loss, and yielded an Lp of 4.07 +/- 1.3 x 10(-8), and after mechanically removing the endothelium, the Lp became 7.73 +/- 2.8 x 10(-8). Using the above data, an Lp could be calculated for aortic endothelium of 8.6 x 10(-8). This suggests that about half the total transmural pressure drop occurs across the endothelium. Scanning electronmicrographs were used to check the condition of the endothelium.
A wearable artificial kidney involving two novel components is proposed. It consists of a turbulent flow ultrafiltering shunt, which supplies 20 liters of ultrafiltrate per day to a disposable activated charcoal cartridge (where creatinine, uric acid, and other tightly bound solutes are adsorbed) and then to an artificial loop of Henle (where the urea is concentrated into 2 liters of ultrafiltrate per day and discarded) from which 18 liters of cleansed, rewarmed ultrafiltrate containing 87% of the glucose is returned to the patient.
Modest increases in intracellular calcium concentrations, in association with ATP depletion, cause the appearance of pathologic changes in erthrocyte shape and deformability. The loss of erythrocyte ATP and simultaneous increase in cellular calcium have previously been considered the sole requisites for the appearance of erythrocyte membrane rigidity. We report that red cells suspended in high-potassium buffers may be simultaneously loaded with calcium (through exposure to the divalent cation ionophore A23187) and depleted of ATP without incurring drastic changes in shape or in membrane stiffness. Incubation of erythrocytes under these conditions effectively blocks both water and potassium loss normally caused by calcium accumulation. However, the high external potassium has no influence on either the ionophore-induced accumulation of calcium or on the the concomitant hydrolysis of cellular ATP. These results suggest the involvement of at least one further parameter, ie, changes in cell water and cation content, in the development of calcium-induced erythrocyte rigidity.
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Previous studies have demonstrated that A23187, an ionophore which selectively transports divalent cations across cell membranes, has profound effects on human erythrocytes: it causes red cells to take up calcium; lose potassium, water, and ATP; convert from biconcave discs to echinocytes and spheroechinocytes; and become more rigid. The present study has explored the influence of calcium uptake induced by the ionophore on the behavior of individual erythrocyte membranes by the micropipette aspiration technique. Exposure of erythrocytes to calcium and A23187 for intervals of up to 30 minutes resulted in marked changes in membrane viscoelastic properties, including the development of increased resistance to aspiration. The most striking manifestation of altered membrane mechanics was apparent after 10 minutes on incubation. Cells pulled into the pipette for a few seconds and the extruded back into the medium retained the deformity imposed by the pipette for several seconds to a few minutes before regaining the form they manifested prior to initial aspiration. The calcium-induced changes in erythrocyte behavior observed in this study strongly support the concept that extrinsic proteins located inside the membrane provide mechanical support to the cell wall, and that increased levels of calcium cause precipitation or cross-linking of the proteins responsible for the increased resistence to deformation and recoil observed after aspiration into micropipettes.
Particles are expected to deposit onto filtering surfaces provided the non-dimensional parameter (see article) U (see article) R2S3/2 exceeds a certain value. For erythrocytes this value has a measured value of 0.15, and for platelets the value ranges from 0.01 to 0.15. If deposition is expected, the rate of particle deposition is proportional to the ultrafiltration flow rate. However, the other fluid mechanic mechanisms may transport a greater number of platelets to the surface. We expect these platelets will be fluid mechanically held to the surface even if it is non-sticky for platelets.
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Red cells which adhere to a surface in a parallel plate flow channel are stretched when acted on by a fluid shear stress. Three types of stretching are studied: whole cell stretching, the stretching of a red cell evagination, and tether (long, thin membrane process) stretching. In addition, the stretching of a large scale model cell attached to a surface is studied in a Couette flow channel. The results indicate that the uniaxial stretching of red cell membrane can be described by a linear stress-strain relationship. Simple theories developed from free body diagrams permit the calculation of a value for the modulus of elasticity of cell membrane in each of the three experiments. In all cases the value for the modulus is on the order of 10(4) dyn/cm(2) for an assumed membrane thickness of 0.01 mum. It was also observed that red cell tethers steadily increase in length when the fluid shear stress is greater than approximately 1.5 dyn/cm(2) and tether lengths in excess of 200 mum have been achieved. Tethers appear to possess both fluid and elastic properties.
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