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J D Hellums

Publications and source records attributed to J D Hellums.

At least 55 records · Page 3Linked to original sources
PubMed1987

Physiological factors affecting O2 transport by hemoglobin in an in vitro capillary system.

O2 transport was examined by measuring the fractional saturation of concentrated hemoglobin solutions flowing through an artificial capillary that was approximately 27 micron in diameter and embedded in a silicone rubber film approximately 170 micron thick. The effects of pH, hemoglobin concentration, O2 tension, temperature, and organic phosphate were measured and analyzed quantitatively by a rigorous mathematical model that included the geometry of the capillary in the silicone film, parabolic flow velocity distributions inside the lumen, and cooperative O2 binding by hemoglobin. The rates of both oxygenation and deoxygenation were limited by diffusion and governed by the magnitude of the O2 gradient between the intracapillary fluid phase and the external gas space. In uptake experiments, O2 flux is determined primarily by the external O2 tension (16-160 mmHg in our experiments) because the internal O2 pressure is kept small due to chemical combination with hemoglobin. In release experiments, the external O2 tension is maintained at zero, and the transport rate is determined by the intracapillary partial pressure of O2 that is proportional to the O2 half-saturation pressure of hemoglobin value of the hemoglobin sample. As a result, factors that change the affinity of hemoglobin for O2, such as pH, temperature, and organic phosphate concentration, influence strongly the rate of O2 release but have little effect on the rate of O2 uptake. These properties are physiologically advantageous, since a decrease in pH or an increase in temperature during exercise increases both the rate and extent of deoxygenation while not altering the kinetics of oxygenation.

Biological Transport↗
PubMed1987

Shear-induced platelet aggregation requires von Willebrand factor and platelet membrane glycoproteins Ib and IIb-IIIa.

Different types of platelets in various types of plasma were subjected to levels of shear stress that produce irreversible platelet aggregation in normal platelet-rich plasma (PRP). At shear stresses of 90 or 180 dyne/cm2 applied for 30 seconds or five minutes, aggregation was either absent or only transient and reversible using severe von Willebrand's disease (vWD) PRP (less than 1% von Willebrand factor, vWF); Bernard-Soulier syndrome (BSS) PRP (platelets deficient in the membrane glycoprotein Ib, GPIb); normal PRP plus monoclonal antibody (MoAb) to GPIb; thrombasthenic PRP (platelets deficient in membrane glycoprotein IIb-IIIa complex, GPIIb-IIIa); and normal PRP plus MoAb to GPIIb-IIIa. Shear-induced aggregation was inhibited under the above conditions, even though the platelets were activated to release their granular contents. Sheared normal platelets in vWD plasma aggregated in response to added vWF. These studies demonstrate that the formation of stable platelet aggregates under conditions of high shear requires vWF and the availability of both GPIb and GPIIb-IIIa on platelet membranes. The experiments demonstrate that vWF-platelet interactions can occur in the absence of artificial agonists or chemical modification of vWF. They suggest a possible mechanism for platelet aggregation in stenosed or partially obstructed arterial vessels in which the platelets are subjected to relatively high levels of shear stress.

Adult↗
PubMed1986

A note on the use of Quin2 in studying shear-induced platelet aggregation.

Quin2, a calcium ion chelator which can penetrate plasma membranes, was used to study the role of intracellular calcium ion concentration in mediating shear-induced platelet activation. Washed platelet suspensions were subjected to various levels of uniform, known shear stress in a cone and plate viscometer in the absence of added agonists. Additional samples were aggregated in response to chemical platelet agonists in a conventional aggregometer. The aggregometer response of Quin2-containing platelets to collagen, thrombin and ADP exhibited increased lag time and reduced maximum rate of aggregation in comparison to controls. However, the extent of aggregation of the Quin2-containing platelets eventually reached the same level as that of the controls. Very different results were obtained for aggregation by shear stress in the viscometer. Shear-induced aggregation was significantly suppressed by Quin2 treatment at both short (30 seconds) and long (300 seconds) times of exposure to the shear field. Shear-induced dense granular release and cellular lysis were unaltered by Quin2 treatment at 30 second exposure times, but both were significantly increased by Quin2 treatment at 300 second exposure times. These results suggest that intracellular calcium ion mobilization is an important early step in shear-induced platelet activation. Additionally, Quin2 appears to have effects resulting in increased platelet fragility. Thus, the findings raise questions on the suitability of Quin2 as an intracellular calcium ion probe in studies in shear fields.

Adenosine Diphosphate↗
PubMed1986

Oxygen transport studies of normal and sickle erythrocyte suspensions in artificial capillaries.

Oxygen transport from normal and sickle erythrocytes was studied under known and carefully controlled conditions simulating the microcirculation. Oxygenated erythrocyte suspensions became deoxygenated as they traversed silicone rubber capillaries of 27 microns diameter. Oxygen saturation values of the flowing erythrocyte suspensions were measured at several axial positions along the capillary by use of a microspectrophotometric technique. Oxygen saturation decreased with increasing distance from the entrance of the capillary and was strongly influenced by the flow rate. Under the same hematocrit and flow conditions, the rate of oxygen saturation decrease was significantly higher for the sickle cells than for normal cells. Sickle cells would be expected to have a higher diffusional resistance to oxygen transport than that of normal cells. However, the lower oxygen affinity of the sickle cells tends to increase the oxygen delivery rate. The difference in oxygen affinity appears to account for the difference in oxygen delivery rates between normal and sickle cells.

Anemia, Sickle Cell↗
PubMed1986

Analysis of shear-induced platelet aggregation with population balance mathematics.

Suspensions of blood platelets aggregate and degranulate when subjected to a shearing flow of sufficient intensity. This work examines, by means of a population balance technique, the kinetics of platelet aggregation in a shear field. The particle collision efficiency, epsilon, and the particle void volume fraction, phi, are estimated from particle number density data. The collision efficiency represents the fraction of particle collisions that result in the binding together of the involved particles. We term epsilon and phi population balance properties because they refer to physical characteristics of platelets and aggregates that are pertinent to their aggregation behavior. Experiments focused on the dependence of epsilon on platelet concentration, shearing rate, and time in a controlled shear field. The collision efficiency is lower in dilute platelet suspensions. This finding supports an ADP-mediated mechanism for shear aggregation. The collision efficiency passes through a maximum with respect to shearing rate, suggesting a competition between the opposing effects of increasing platelet activation and increasing collision violence. The collision efficiency is highest during the first ten seconds in the shear field and declines significantly thereafter. Even at its maximum, however, epsilon for shear aggregation is small: only about one in every thousand particle collisions results in binding.

Adult↗
PubMed1986

Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation.

A fluid shear stress of 180 dyn/cm2 was applied for 0.5 and 5 min to platelets in citrated plasma or blood in a cone and plate viscometer with minimal platelet-surface interactions. Platelets aggregated in the shear field if large von Willebrand Factor (vWF) multimers were present. Aggregation did not require ristocetin, other exogenous agents, or desialation of vWF. Unusually large vWF multimers produced by human endothelial cells were functionally more effective than the largest plasma vWF forms in supporting shear-induced aggregation. Shear-induced aggregation was inhibited by monoclonal antibodies to platelet glycoprotein Ib or the IIb/IIIa complex, but was little affected by the absence of fibrinogen. vWF-dependent platelet aggregation under elevated shear stress in partially occluded vessels of the arterial microcirculation may contribute to thrombosis, especially if unusually large vWF multimers are released locally from stimulated or disrupted endothelial cells.

Adenosine Diphosphate↗
PubMed1984

The kinetics of platelet aggregation induced by fluid-shearing stress.

The work herein examines in vitro the kinetics of platelet aggregation in response to the fluid-shearing stress imparted by a rotational viscometer. Aggregation is expressed through changes in particle size histograms and total particle count. Platelet aggregation commenced above 2000 sec-1 shear rate and was stable above 5000 sec-1. Activation by shear required less than 10 sec at all shear rates. At shear rates above 5000 sec-1, the particle count fell by one-half within 10 sec. By this point aggregates of 1000 platelets or more had appeared. Diluting the platelet suspensions suppressed shear-induced aggregation but not aggregation to ADP, supporting the hypothesis that shear-induced platelet aggregation proceeds through chemical release.

Adult↗
PubMed1983

A simple model for simulation of oxygen transport in the microcirculation.

A mathematical model of deoxygenation of blood in the microcirculation is used to estimate the mass transfer resistance in the blood and to examine certain assumptions used in prior work on simulation of the microcirculation: the treatment of blood as a continuum and the use of a single-step reaction kinetics model. The erythrocytes are treated as cylindrical slugs which alternate with plasma gaps such that oxygen transport is by radial diffusion in the cell. The system of equations including reaction kinetics and oxyhemoglobin diffusion is solved numerically. The results are of direct applicability in estimation of oxygen concentration profiles in tissue. The results also indicate that the resistance to oxygen transport in the capillary (relative to that in the surrounding tissue) is much higher than predicted by the continuum approach used by most prior workers. The resistance in the capillary is a significant fraction of the overall resistance. Other results give quantitative estimates of the error incurred from use of a single-step kinetic model.

Biological Transport↗
PubMed1981

The effect of PGI2 and theophylline on the response of platelets subjected to shear stress.

A specially designed rotational viscometer was used to investigate the effects of the antiplatelet agent PGI2 in combination with theophylline on the response of human platelets subjected to shear stress. Samples of citrated platelet-rich plasma (PRP) were exposed to shear stress in the viscometer for a period of 5 min at 23 degrees C. The levels of stress studied ranged from 50 to 300 dynes/sq cm. Pretreatment of the platelets with 0.01 microM PGI2 and 500 microM theophylline before exposure to shear stress caused a large reduction in shear-induced platelet aggregation. However, it was also observed that the PGI2--theophylline pretreatment concomitantly caused a large increase in shear-induced platelet lysis and serotonin release at stress levels equal to or greater than 150 dynes/sq cm. This observed increase in platelet fragility may have important implications for clinical applications of PGI2. The results are discussed and compared to those obtained in prior work in which platelets were pretreated with acetylsalicylic acid or with PGE1.

Adenosine Diphosphate↗