PubMed Health⌕ Search

Biomedical subjects

J D Hellums

Publications and source records attributed to J D Hellums.

At least 73 records · Page 4Linked to original sources
PubMed1978

Platelet lysis and aggregation in shear fields.

A rotational viscometer was used to study the effects of shear stress on platelets in human platelet-rich plasma (PRP). For 5-min exposure times, shear stresses above 160 dynes/cm2 induced platelet lysis (as determined by release of platelet lactic dehydrogenase). For 30-s exposure times, shear stresses greater than 600 dynes/cm2 were required to induce platelet lysis. The platelet counts of sheared PRP were decreased to as low as one-fifth the original count due largely to shear-induced aggregation. The count is a minimum at intermediate stress levels (200-400 dynes/cm2). Higher stresses induce disaggregation as well as lysis. The diminution in the counts was partially reversed in 2 h incubation after cessation of shearing. Experiments were carried out with three different viscometer configurations so that the shear stress and the solid surface area access could be varied independently. Surface access was not a significant variable in the conditions of the experiments. Thus aggregation and lysis may be induced by stress effects alone as well as by solid surface effects. The results also show that the response of platelets to shear stress is strongly dependent on exposure time. Platelets are much less resistant to shear stress than red cells for relatively long exposure times. However, the converse is true for very short exposure times.

Blood Platelets↗
PubMed1975

Fragility of abnormal erythrocytes evaluated by response to shear stress.

Shear stress is a potential cause of erythrocyte fragmentation and hemolysis in flowing blood. In this study, the response of abnormal human erythrocytes to shear stress in virto was evaluated using a concentric cylinder viscometer. Compared to normal red cells, deoxygenated erythrocytes from persons with sicle cell anemia were particularly susceptible to fragmentation and hemolysis by shear stress. Oxygenation of sicke cell blood improved the resistance of those red cells to shear stress; they remain, however, more susceptible to shear stress than normal erythrocytes. Erythrocytes from patients with iron deficiency, thalassemia minor, and erythrocyte pyruvate kinase deficiency showed fragmentation and hemolysis at threshold shear stresses intermediate between those ovserved for blood from patients with sickle cell anemia and normal persons. Blood samples from patients with hereditary spherocytosis were more resistant to shear stress than normal blood. These results indicate that there are important differences in the response of various red cells to shear stress.

Anemia, Hypochromic↗
PubMed1975

Morphological, biochemical, and functional changes in human platelets subjected to shear stress.

Thromboembolic complications associated with cardiovascular prostheses are thought to result from activation of coagulation factors or platelets by surface contact and/or by certain physical forces generated at the interface between the foreign material and blood. Studies of the effects on human platelets of one of these physical forces, shear stress, were made. A rotational viscometer was used to apply graded levels of shear stress to platelet-rich plasma. Very low shear stress (50 dynes per square centimeter) resulted in the liberation of small amounts of ATP, ADP, and serotonin and subsequent platelet aggregation. Stresses of 100 dynes per square centimeter or more resulted in the appearance in plasma of nonstorage nucleotides, indicating cell lysis, and shear stresses of 250 dynes per square centimeter or more resulted in the fragmentation of platelets. Shear-induced platelet aggregation was partially reversible but only those samples subjected to low levels of shear stress recovered their ability to aggregate to the subsequent addition of ADP. These studies indicate that platelets are extremely sensitive to shear stress and raise the possibility that thrombus formation and/or accelerated platelet turnover in patients with rheumatic valvular disease or who possess artificial heart valves or other cardiac prosthetic devices could result from the effects of this physical force on circulating platelets.

Adenosine Diphosphate↗
PubMed1972

Red blood cell damage by shear stress.

A series of careful studies has been made on blood damage in a rotational viscometer. Specific attention has been focused on the effects of solid surface interaction, centrifugal force, air interface interaction, mixing of sheared and unsheared layers, cell-cell interaction, and viscous heating. The results show that there is a threshold shear stress, 1500 dynes/cm(2), above which extensive cell damage is directly due to shear stress, and the various secondary effects listed above are negligible. By analysis of these results and those of prior workers it is shown that the exposure time-shear stress plane is divided into two distinct regimes. In the regime of relatively low stresses and exposure times there is relatively little damage, and the damage is dominated by solid surface interaction effects. In the other regime, at high stresses and exposure times, stress effects alone dominate and very high rates of hemolysis occur. The experimental findings of all prior workers are shown to be consistent when interpreted in this way.

Centrifugation↗
PubMedDate not supplied

1993 Whitaker Lecture: biorheology in thrombosis research.

A review is presented on biorheological studies of platelet activation and platelet-platelet binding events that play key roles in thrombosis and hemostasis. Rheological methods have been used by a number of workers to establish the importance of fluid mechanical shear stress as a determinate of platelet reactions. Fluid mechanical shear stress can be regarded as a platelet agonist that is always present in the circulation and that is synergistic in its actions with other agonists. Early biorheological studies were phenomenological in that they focused on stress effects on measures of platelet function. Subsequent studies have elucidated mechanisms and have shown that the biochemical pathways of platelet activation are very different at elevated shear stresses than in the low shear stress environment used in many platelet activation studies. This finding that biochemical pathways of platelet activations are different at different shear stress levels suggests that it may be possible to develop platelet inhibitors of highly specific action: it may be possible to inhibit pathways important in thrombosis in a partially occluded artery without seriously compromising the normal hemostatic function of platelets. Another aspect of the work suggests that the biorheological approach may make it possible to develop better methods for prediction of thrombotic tendencies in human subjects.

Hemorheology↗
PubMedDate not supplied

Direct demonstration of radiolabeled von Willebrand factor binding to platelet glycoprotein Ib and IIb-IIIa in the presence of shear stress.

In this study it is demonstrated for the first time that shear stress induces the binding of exogenous von Willebrand factor (vWF) multimers to platelets. The vWF preparations used were: 125I-vWF purified from human cryoprecipitate (and including all vWF multimers present in normal plasma); and 35S-cysteine-vWF secreted by human umbilical vein endothelial cells (HUVECs) (and containing unusually large vWF forms, as well as all plasma-type vWF multimers). Direct shear-induced binding to washed platelets (300-360 x 10(3)/microliters) of radiolabeled vWF was maximum at 60-120 dynes/cm2 evaluated at 30 sec and was in extent about one-quarter of the binding stimulated by ristocetin after 3 min of incubation. The shear-induced binding of only a small percentage of added radiolabeled vWF was sufficient to initiate aggregation. Radiolabeled vWF attached to both glycoprotein (GP) Ib and GPIIb-IIIa receptors in the shear field, with complete inhibition of binding occurring with simultaneous blockade of both receptors. Binding was potentiated by ADP released from sheared platelets.

Antibodies, Monoclonal↗
PubMedDate not supplied

Simulation of intraluminal gas transport processes in the microcirculation.

Intraluminal resistance to gas transport between the microcirculation and tissue was neglected for a half-century following the early work of Krogh. In recent years it has come to be understood that this neglect is seriously in error. This paper reviews the background for the long period of misdirection, and progress in placing the simulation of gas transport processes on a more accurate, quantitative basis.

Acid-Base Equilibrium↗
PubMedDate not supplied

Epinephrine and shear stress synergistically induce platelet aggregation via a mechanism that partially bypasses VWF-GP IB interactions.

Elevated shear stress levels in pathologically stenosed vessels induce platelet activation and aggregation, and may play a role in the pathogenesis of arterial disease. Increased plasma catecholamine concentrations have also been implicated in the onset of acute coronary ischemic syndromes. This study was designed to examine the synergistic interaction of shear stress and epinephrine in the activation of platelets. Platelets (in PRP) sheared at 60 dyn/cm2 showed little or no aggregation unless pretreated with epinephrine. Pretreatment with 250 nM epinephrine followed by shear at 60 dyn/cm2 induced > 60% platelet aggregation. The specific alpha 2-adrenergic receptor antagonist yohimbine inhibited the synergistic aggregation, as did the ADP scavenging system phosphocreatine/creatine phosphokinase, indicating a three-way synergism with ADP. Chemical or monoclonal antibody blockade of von Willebrand factor (vWF) interactions with either platelet glycoprotein (Gp) Ib or Gp IIb/IIIa completely inhibited platelet aggregation induced by activating levels of shear stress alone. However, the combination of epinephrine and shear stress induced platelet aggregation that was blocked by 10E5, a monoclonal antibody that inhibits vWF binding to Gp IIb/IIIa, but not by aurin tricarboxylic acid or the monoclonal antibody 6D1, both of which inhibit vWF binding to Gp Ib. Synergistic platelet aggregation in response to epinephrine and shear stress was observed in washed platelets, platelet-rich plasma and whole blood in vitro, and also ex vivo following exercise to elevate endogenous levels of catecholamines. These results indicate that epinephrine synergizes with shear stress to induce platelet aggregation. This synergistic response requires functional Gp IIb/IIIa complexes, but is at least partially independent of vWF-Gp Ib interactions.

Calcium↗
PubMedDate not supplied

Shear stress-induced binding of von Willebrand factor to platelets.

Shear stress-induced platelet aggregation requires von Willebrand factor (vWF), platelet glycoprotein (GP) Ib, GPIIb-IIIa, Ca2+, and adenosine diphosphate (ADP). Recent reports using vWF labeled with either 125I or fluorescein isothiocyanate (FITC) have demonstrated that in shear-fields, vWF binds to both GPIb and GPIIb-IIIa. The sequence of the vWF finding to the two platelet receptors has not been precisely determined in these reports. In this study, a flow cytometry technique using a primary anti-vWF antibody and a secondary FITC IgG antibody was used to measure shear stress-induced vWF binding to platelets. Washed normal platelets suspended at 50,000/microliters with purified large vWF multimers were exposed to laminar shear stresses of 15 to 120 dynes/cm2 for 30 sec. At this low platelet count, little or no aggregation occurred in the shear fields. A significant increase in post-shear vWF-positive platelets was consistently observed. Experiments with platelets from normal and severe von Willebrand's disease (vWD) (which lack plasma and platelet alpha-granule vWF) demonstrated that exogenous vWF predominately contributed to the platelet-vWF binding. Blockade of platelet GPIb with the monoclonal anti-GPIb antibody, 6D1, completely inhibited shear stress-induced platelet-vWF attachment. In contrast, blockade of GPIIb-IIIa with monoclonal anti-GPIIb-IIIa antibodies, 10E5, or c7E3, or with the GPIIb-IIIa-blocking tetrapeptide, RGDS had little or no inhibitory effect on platelet-vWF binding. These data demonstrate that the binding of vWF to GPIb is likely to be the initial shear-induced platelet-ligand binding event.

Blood Platelets↗