scholarly journals Cryopreservation moderates the thrombogenicity of arterial allografts during storage

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255114
Author(s):  
László Hidi ◽  
Erzsébet Komorowicz ◽  
Gergely Imre Kovács ◽  
Zoltán Szeberin ◽  
Dávid Garbaisz ◽  
...  
Keyword(s):  
Cross Sections ◽  
Time Window ◽  
Therapeutic Option ◽  
Shear Rates ◽  
Potential Clinical Benefit ◽  
Duration Of Storage ◽  
Platelet Deposition ◽  
Vascular Infections ◽  
The Media ◽  
Thrombogenic Potential

Introduction Management of vascular infections represents a major challenge in vascular surgery. The use of cryopreserved vascular allografts could be a feasible therapeutic option, but the optimal conditions for their production and use are not precisely defined. Aims To evaluate the effects of cryopreservation and the duration of storage on the thrombogenicity of femoral artery allografts. Methods In our prospective study, eleven multi-organ-donation-harvested human femoral arteries were examined at five time points during storage at -80°C: before cryopreservation as a fresh native sample and immediately, one, twelve and twenty-four weeks after the cryopreservation. Cross-sections of allografts were perfused with heparin-anticoagulated blood at shear-rates relevant to medium-sized arteries. The deposited platelets and fibrin were immunostained. The thrombogenicity of the intima, media and adventitia layers of the artery grafts was assessed quantitatively from the relative area covered by fibrin- and platelet-related fluorescent signal in the confocal micrographs. Results Regression analysis of the fibrin and platelet coverage in the course of the 24-week storage excluded the possibility for increase in the graft thrombogenicity in the course of time and supported the hypothesis for a descending trend in fibrin generation and platelet deposition on the arterial wall. The fibrin deposition in the cryopreserved samples did not exceed the level detected in any of the three layers of the native graft. However, an early (up to week 12) shift above the native sample level was observed in the platelet adhesion to the media. Conclusions The hemostatic potential of cryopreserved arterial allografts was retained, whereas their thrombogenic potential declined during the 6-month storage. The only transient prothrombotic change was observed in the media layer, where the platelet deposition exceeded that of the fresh native grafts in the initial twelve weeks after cryopreservation, suggesting a potential clinical benefit from antiplatelet therapy in this time-window.

Physical and Enzymatic Perturbation of the Architecture of the Tunica media Destroys its Inherent Thromboresistance

2002 ◽  
Vol 88 (11) ◽  
pp. 827-833 ◽  
Author(s):  
Erzsebet Komorowicz ◽  
Robert McBane ◽  
David Fass
Keyword(s):  
Cross Sections ◽  
Binding Sites ◽  
Serine Proteases ◽  
Vessel Wall ◽  
Balloon Dilation ◽  
Fold Increase ◽  
Biochemical Processes ◽  
Platelet Deposition ◽  
The Media ◽  
Media Layer

SummaryThe media layer of the arterial cryo-cross sections, is defective for vWf-dependent platelet adhesion. Exposure of the same layer by stripping off the most inner portions of the vessel wall results in a highly thrombogenic surface. Stripping or balloon dilation was applied to porcine arteries prior to functional assays. Cryosections of treated or untreated arteries were perfused with porcine blood at 3350 s-1 and platelet deposition was detected by indirect immunofluorescence. Following balloon dilation, vWf-dependent platelet deposition increased; covering 9.08 ± 1.36% of the total media surface area, this value for untreated vessels was 0.88 ± 0.14%. A 10-fold increase was also found in the binding of vWf-coated fluorescent beads to the media. In addition to mechanical procedures, treatment by serine-proteases like trypsin, chymotrypsin and proteinase 3, or by chondroitinase ABC, but not by heparitinase also resulted in a 7-10-fold increase in platelet coverage over the media. Collagen in the media may be complexed with another vessel wall component shielding the vWf-binding sites. Mechanical or biochemical processes unmask these sites, and increase the thrombogenicity of the vessel wall.

Asialo von Willebrand Factor Enhances Platelet Adhesion to Vessel Subendothelium

1988 ◽  
Vol 60 (01) ◽  
pp. 030-034 ◽  
Author(s):  
Eva Bastida ◽  
Juan Monteagudo ◽  
Antonio Ordinas ◽  
Luigi De Marco ◽  
Ricardo Castillo
Keyword(s):  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Human Albumin ◽  
Membrane Receptors ◽  
Shear Rates ◽  
High Shear Rates ◽  
Platelet Deposition ◽  
Platelet Spreading ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryNative von Willebrand factor (N-vWF) binds to platelets activated by thrombin, ADP or ristocetin. Asialo vWF (As-vWF) induces platelet aggregation in absence of platelet activators. N-vWF mediates platelet adhesion to vessel subendothelium at high shear rates. We have investigated the role of As-vWF in supporting platelet deposition to rabbit vessel subendothelium at a shear rate of 2,000 sec-1, using the Baumgartner perfusion system. We have studied the effects of the addition of As-vWF (from 2 to 12 μg/ml) to perfusates consisting of washed red blood cells, 4% human albumin and washed platelets. Our results show a significant increase in platelet deposition on subendothelium (p <0.01) in perfusions to which As-vWF had been added. Blockage of the platelet glycoproteins Ib and IIb/IIIa (GPIb and GPIIb/IIIa) by specific monoclonal antibodies (LJIb1 and LJCP8, respectively) resulted in a decrease of platelet deposition in both types of perfusates prepared with N-vWF and As-vWF. Our results indicate that As-vWF enhances platelet deposition to vessel subendothelium under flow conditions. Furthermore, they suggest that this effect is mediated by the binding of As-vWF to platelet membrane receptors, which in turn, promote platelet spreading and adhesion to the subendothelium.

Radical schemes for the implementation of section structures of the RADICAL language when modeling complex purposeful system

2021 ◽  
Author(s):  
M.V. Pirogov
Keyword(s):  
Complex System ◽  
Cross Sections ◽  
Problem Area ◽  
Information Support ◽  
Existing Problems ◽  
Modeling Technology ◽  
Universal Language ◽  
The Media ◽  
Modeling Complex System ◽  
Automation Tools

Complex artificial purposeful systems and their software and hardware are characterized not only by achievements, but also disadvantages leading to significant losses. Modern automation tools do not fully cope with the existing problems. To solve the problems of complex systems, new effective tools are needed, new modeling technology. This technology should cover all significant aspects of the problem area. It seems that such technology should be based on radical modeling and the universal language of radical schemes RADICAL. A radical is a system characterized by both active (working) and passive states. Being connected with each other radicals form schemes of radicals. These schemes are constructions of the RADICAL language. In the aggregate, these schemes realize radical environment – radical model of united problem area of complex system. That is, the problem area is represented by a single global scheme of radicals. The work with such a scheme is carried out using the universal language of radical schemes RADICAL, applicable to the problem area of any complex system by constructing sections of the RADICAL language, expressed by the schemes of radicals. The purpose of the work is to consider the use of radical schemes for the implementation of the structures of sections (sequences of sections) of the RADICAL language when modeling complex system. The results of the work are descriptions of some typical schemes of radicals intended for the implementation of the section structures of the RADICAL language when modeling complex purposeful systems. Something significant sequences of sections are considered. The practice of using of structures of cross-sections of the media of radicals, expressed by the schemes of radicals, indicates the expediency of they use for radical modeling of problem areas of complex purposeful systems, for the development and modification of software and information support of such systems.

Recombinant Activated FVII (rFVIIa) Corrects Platelet Dysfunction in Hemophilic Patients: Study on Collagen and Tissue Factor Surfaces at High Shear Rates.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4034-4034
Author(s):  
Raul Tonda ◽  
Ana M. Galan ◽  
Irene Lopez-Vilchez ◽  
Marcos Pino ◽  
Antonio Ordinas ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Cross Sections ◽  
Platelet Adhesion ◽  
Hemophilia A ◽  
Severe Hemophilia ◽  
Platelet Dysfunction ◽  
Blood Samples ◽  
Shear Rates ◽  
High Shear Rates ◽  
Exogenous Addition

Abstract Hemophilic patients suffer bleeding episodes despite having a normal bleeding time. A possible platelet dysfunction in these patients has not been deeply investigated. rFVIIa improves hemostasis of hemophilic patients, even in those who develop inhibitors. Clinical efficacy of this drug has been widely confirmed, though, its mechanism of action is not fully understood. We used the PFA-100® with specially devised cartridges whose membrane apertures were coated with collagen alone (COL) or collagen-tissue factor (COL-TF). Blood samples from normal donors or from a group of patients with severe hemophilia A, were anticoagulated with low molecular weight heparin (LMWH). We tested the ability of rFVIIa to shorten the closure times under the previous conditions. The structure of the hemostatic plugs formed on the membrane apertures were further analyzed using light microscopy on thin cross-sections. Closure times were statistically prolonged in blood samples from hemophilic patients tested with COL cartridges (255±22 s.vs.187±15 s in normal donors; p&lt;0.05). Presence of TF in the apertures (COL-TF) caused a 20% shortening in closure times, both in normal donors and in hemophilic patients. Exogenous addition of 10 μg/ml rFVIIa to blood samples from hemophilic patients induced a further statistically significant reduction of closure times (p&lt;0.05). This further reduction in closure times was not observed in blood samples drawn from normal individuals. Microscopical analysis of the plugs formed on the apertures showed that occlusive thrombi formed in the presence of TF are more compact and have higher occlusive capacity. Addition of FVIIa led to the formation of more organized platelet plugs which appeared further consolidated with fibrin strands within platelet masses. Patients with severe hemophilia showed platelet dysfunction that could be detected with the PFA-100® using specific cartridges. It is likely that the platelet dysfunction observed in these patients could be related to concurrent reductions in VWF that could affect platelet adhesion in these patients revealed at the very elevated shear rates used in the PFA-100®. Under these conditions, TF deposited onto the collagen-coated apertures proved to play a significant role in the initiation of hemostasis. rFVIIa improved the recruitment of platelets on COL-TF and contributed to a partial correction of the platelet dysfunction observed in patients with hemophilia A as further confirmed by the formation of more efficient aggregates in the PFA-100. In essence, rFVIIa circumvented a pre-existent platelet adhesion defect in hemophiliac patients. The pro-hemostatic action of rFVIIa was not observed in parallel studies with blood from healthy donors, indirectly suggesting a good safety profile for this agent when hemostasis is well preserved. PFA-100 could be considered as a possible monitoring system of FVIIa when hemostasis is impaired.

scholarly journals Evidence for a general neural signature of face familiarity

2021 ◽  
Author(s):  
Alexia Dalski ◽  
Gyula Kovács ◽  
Géza Gergely Ambrus
Keyword(s):  
Right Hemisphere ◽  
Time Window ◽  
Event Related Potentials ◽  
Central Regions ◽  
Related Potentials ◽  
The Media ◽  
Neural Signature ◽  
Cross Experiment ◽  
Strong Candidate ◽  
The Right

We explored the neural signatures of face familiarity using cross-participant and cross-experiment decoding of event-related potentials, evoked by unknown and experimentally familiarized faces from a set of experiments with different participants, stimuli, and familiarization-types. Participants were either familiarized perceptually, via media exposure, or by personal interaction. We observed significant cross-experiment familiarity decoding involving all three experiments, predominantly over posterior and central regions of the right hemisphere in the 270 - 630 ms time window. This shared face familiarity effect was most prominent between the Media and Personal, as well as between the Perceptual and Personal experiments. Cross-experiment decodability makes this signal a strong candidate for a general neural indicator of face familiarity, independent of familiarization methods and stimuli. Furthermore, the sustained pattern of temporal generalization suggests that it reflects a single automatic processing cascade that is maintained over time.

Upstream Thrombus Growth Impairs Downstream Thrombogenesis in Non-Anticoagulated Blood: Effect of Procoagulant Artery Subendothelium and Non-Procoagulant Collagen

1991 ◽  
Vol 65 (05) ◽  
pp. 596-600 ◽  
Author(s):  
Kjell S Sakariassen ◽  
Harvey J Weiss ◽  
Hans R Baumgartner
Keyword(s):  
Shear Rate ◽  
Tissue Factor ◽  
Platelet Adhesion ◽  
Rabbit Aorta ◽  
Axial Position ◽  
Fibrillar Collagen ◽  
Fibrin Deposition ◽  
Clotting Factors ◽  
Shear Rates ◽  
Platelet Deposition

SummaryIn the present experiments we have investigated the influence of wall shear rate and axial position on platelet and fibrin deposition which results when flowing human non-anticoagulated blood is exposed to either non-procoagulant fibrillar collagen (human type III) or procoagulant subendothelium (rabbit aorta). Platelet adhesion, thrombus volume and fibrin deposition were morphometrically evaluated at axial positions of 1 and 13 mm following perfusions for 5 min at shear rates of 100, 650 and 2,600 s-1.An axially-dependent decrease of platelet adhesion (34-57%, p <0.01-0.05) and thrombus volume (57-80%, p <0.05) was observed on collagen at all shear rates. On subendothelium, an axially-dependent decrease was observed for platelet adhesion only at 100 s-1 (29% ; p <0.01) and for thrombus volume at shear rates of 650 s-1 and above (49-58%, p <0.01). Deposition of fibrin on subendothelium was axially decreased (16-42%, p <0.05) at all shear rates, while no significant axial differences were seen on collagen. However, substantially more fibrin was deposited on the subendothelium (p <0.05), and the upstream platelet adhesion and thrombus volume were lower than on collagen (p <0.05) at 100 s-1 and 650 s-1. The axially-dependent phenomena on the two surfaces are consistent with the concept of rapid-growing upstream thrombi which deplete the blood layer streaming adjacent to the surface of platelets, leading to decreased platelet deposition farther downstream. The observations suggest that deposition of fibrin is enhanced by subendothelial tissue factor, and that upstream depletion of clotting factors may lower the downstream deposition of fibrin, analogous to the depletion of platelets.

The Effect of Platelet PlA Polymorphism on Experimental Thrombus Formation in Man Depends on Blood Flow and Thrombogenic Substrate

2001 ◽  
Vol 85 (06) ◽  
pp. 1097-1103 ◽  
Author(s):  
Kjell Sakariassen ◽  
Hélène Grandjean ◽  
Claire Thalamas ◽  
Bernard Boneu ◽  
Pierre Sié ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Flow Properties ◽  
Shear Rates ◽  
Perfusion Chamber ◽  
Platelet Receptor ◽  
Platelet Deposition ◽  
Coronary Syndromes ◽  
Platelet Thrombus

SummaryA number of studies have reported conflicting data on the association of the PlA1/PlA2 polymorphism of the GPIIIa gene and coronary syndromes. We have investigated the effect of this polymorphism on experimental platelet thrombus formation in man. Forty healthy male volunteers were genotyped for the PlA1/PlA2 polymorphism. Thrombus formation was induced ex vivo by exposing a tissue factor (TF) or a collagencoated coverslip in a parallel plate perfusion chamber to native blood for 2 and 4 min. The shear rates at these surfaces were 650 and 2,600 s–1. Platelet and fibrin deposition was quantified by immunoenzymatic methods. The frequencies of PlA1/PlA1 and PlA1/PlA2 genotypes were 52.5% and 47.5%, respectively. Ex vivo deposition of fibrin on TF was not affected by the PlA1/PlA2 polymorphism. However, the ex vivo platelet deposition at 650 s–1 was higher in blood from PlA1/PlA1 individuals than in PlA1/PlA2 individuals (P = 0.008 at 4 min). On collagen, neither fibrin nor platelet deposition was significantly affected by the PlA1/PlA2 polymorphism. Platelet thrombus formation is significantly influenced by genetic variations in the GPIIIa platelet receptor. This effect depends on the blood flow properties and the nature of the thrombogenic stimulus.

Significance of infection markers and microbiological findings during tissue processing of cryopreserved arterial homografts for the early postoperative course

VASA ◽  
2009 ◽  
Vol 38 (4) ◽  
pp. 365-373 ◽  
Author(s):  
Bisdas ◽  
Mattner ◽  
Ott ◽  
Pichlmaier ◽  
Wilhelmi ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Therapeutic Option ◽  
Graft Infection ◽  
Tissue Bank ◽  
Enterobacter Aerogenes ◽  
Prosthetic Graft ◽  
Multiple Organ ◽  
Postoperative Course ◽  
Prosthetic Graft Infection ◽  
Vascular Infections

Background: To evaluate homograft implantation for the urgent treatment of vascular infections on the basis of the course of infection using microbiological findings in perioperatively obtained specimens and during homograft processing. Patients and methods: 85 patients were treated with cryopreserved homografts from 2004-2007. The microbiological findings of the decontamination process of homografts in the tissue bank were evaluated. The perioperative infection profile (microorganisms, CRP, leukocytes, body temperature) of the patients was analysed. Results: Complete microbiological and clinical follow-up for the postoperative course was available for 35 patients, who were treated with homografts from the same tissue bank and finally included into this study. 55 cryopreserved homografts were implanted. 35 / 55 (64 %) homografts were positive for microorganisms before decontamination. 3 / 35 (9 %) homografts remained positive after the decontamination. 33 patients were operated for prosthetic graft infection and 2 for an infiltration of a large vessel from neighbouring malignant disease. The most common infection agent was Staphylococcus aureus. Thirty-day mortality was 20 % (7 / 35). Only in 4 / 35 (11 %) patients were the microorganisms of the intraoperative swabs also detected during the postoperative course. The microorganisms were ORSA, Enterococcus faecium, Enterobacter aerogenes and Burkholderia cepacia. The patient with ORSA infection died on POD 11 from multiple organ failure and all other patients recovered. None of the postoperative swabs showed the homograft predecontamination microorganisms. Interestingly, a significant association (P = 0.003) between C-reactive protein increase two weeks after surgery and donor-recipient ABO mismatch was found. Conclusions: The implantation of homografts following the established decontamination is an alternative urgent therapeutic option in vascular infections with encouraging outcomes. The absence of the predecontamination focus in the postoperative specimens of patients, suggests that the postoperative course and outcomes show no strong relation to potential homograft contamination prior to the decontamination process.

Correlation between Real-Time Microvascular Abnormalities and Whole Blood Viscosity (WBV) in Type-2 Diabetes Mellitus (T2DM) Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3909-3909
Author(s):  
Anthony T. Cheung ◽  
Sahana Ramanujam ◽  
Michelle A. Barbosa ◽  
Violet K. Asfour ◽  
Maria V. Medina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Early Detection ◽  
Real Time ◽  
Disease Severity ◽  
Time Window ◽  
Computer Assisted ◽  
Whole Blood Viscosity ◽  
Shear Rates ◽  
Control Subjects

Abstract Novel technologies were used to study the microvascular abnormalities in Type-2 diabetes mellitus (T2DM) patients and to correlate these real-time pathological complications with whole blood viscosity (WBV) over a wide range of shear rates (1–1,000s−1). Computer-assisted intravital microscopy (CAIM) was used to non-invasively and objectively quantify the microvascular abnormalities in the conjunctival microcirculation in T2DM patients (n=12; age range = 45 to 68) and healthy non-diabetic control subjects, with the medical history of each subject blinded to the investigators. Fifteen recognizable microvascular abnormalities existed in T2DM patients and not in the control subjects, though not all the abnormalities were found in each patient. A severity index (SI) -- the arithmetic sum of microvascular abnormalities in each patient quantified via CAIM -- was computed to give a score to correlate with medical history, WBV and shear rates. T2DM SI (6.9±1.7) differed significantly (P<0.01) from control SI (0.6±0.7) and correlated significantly with disease severity, but not with the duration of the disease since diagnosis. The results, together with results from a previous study, lend support to the hypothesis that diabetic complications may have occurred in the pre-diabetic period; indicative of the existence of a “time window” before the onset of clinically detectable hyperglycemia. To adequately assess WBV to correlate with T2DM SI, a computer-assisted scanning capillary viscometer, the Rheolog™, was used to generate a viscosity profile for each patient or control subject over a range of shear rates (1 to 1,000s−1) using one 3-ml citrated venous blood sample from each subject. Based on the viscosity profiles generated, WBV of T2DM patients at various shear rates differed significantly from control values. For example, averaged WBV of T2DM patients at a shear rate of 300s−1 (4.01±0.33cp) differed significantly (P<0.02) from averaged WBV of control subjects (3.34±0.05cp). WBV correlated with SI of T2DM patients, disease severity and medical records. This correlation may have unique clinical implications - it can be used to study shear-stress induced pathogenesis on endothelial dysfunction in various vascular diseases and in early detection of T2DM in carriers (e.g. siblings of T2DM patients) before clinical diagnosis of T2DM during the pre-diabetic “time window” of early detection. Follow-up studies on the correlation between real-time microvascular abnormalities (SI), disease severity, WBV and shear rates in Alzheimer’s Disease patients and in early detection of T2DM are in progress.

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