5065Platelet desialylation induced by high shear-stress mechanical circulatory support

A model is proposed by which the formation of the vascular network in animals proceeds via progressive penetration of the vessel ramification into a capillary mesh, by means of a laplacian growth mechanism of hydrodynamical origin. In this model, the growth of both arteries and veins follows the directions of high shear stress provoked by the blood flow on the endothelial wall of a pre-existing capillary mesh. This process is shown to be identical to the phenomenon of dendritic growth, which is responsible for the formation of such well-known patterns as dendritic crystals, lightning sparks or branching aggregates of bacteria. A number of straightforward consequences of potentially important medical and physiological interests are deduced. These include the natural and spontaneous organization of the arterial and venal trees, the spontaneous and unavoidable tropism of arteries towards veins and vice-versa, the hierarchical character of the vessels and the possibility of computerized prediction of the vascular pattern from the shape of the capillary bed.

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On-Chip Platelet Activation Assessment: Microfluidic Emulation of Shear Stress Profiles Induced by Mechanical Circulatory Support Devices

10.1007/978-1-0716-1693-2_12 ◽

2021 ◽

pp. 201-212

Author(s):

Tatiana Mencarini ◽

Silvia Bozzi ◽

Alberto Redaelli

Keyword(s):

Shear Stress ◽

Platelet Activation ◽

Mechanical Circulatory Support ◽

Circulatory Support ◽

Mechanical Circulatory Support Devices ◽

Stress Profiles ◽

On Chip ◽

Support Devices

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Mechanical shear stress and leukocyte phenotype and function: Implications for ventricular assist device development and use

The International Journal of Artificial Organs ◽

10.1177/0391398818817326 ◽

2018 ◽

Vol 42 (3) ◽

pp. 133-142 ◽

Cited By ~ 1

Author(s):

Gemma Radley ◽

Sabrina Ali ◽

Ina Laura Pieper ◽

Catherine A Thornton

Keyword(s):

Heart Failure ◽

Shear Stress ◽

Mechanical Circulatory Support ◽

Circulatory Support ◽

Modern World ◽

Mechanical Trauma ◽

Ventricular Assist ◽

End Stage ◽

And Function ◽

The Impact

Heart failure remains a disease of ever increasing prevalence in the modern world. Patients with end-stage heart failure are being referred increasingly for mechanical circulatory support. Mechanical circulatory support can assist patients who are ineligible for transplant and stabilise eligible patients prior to transplantation. It is also used during cardiopulmonary bypass surgery to maintain circulation while operating on the heart. While mechanical circulatory support can stabilise heart failure and improve quality of life, complications such as infection and thrombosis remain a common risk. Leukocytes can contribute to both of these complications. Contact with foreign surfaces and the introduction of artificial mechanical shear stress can lead to the activation of leukocytes, reduced functionality and the release of pro-inflammatory and pro-thrombogenic microparticles. Assessing the impact of mechanical trauma to leukocytes is largely overlooked in comparison to red blood cells and platelets. This review provides an overview of the available literature on the effects of mechanical circulatory support systems on leukocyte phenotype and function. One purpose of this review is to emphasise the importance of studying mechanical trauma to leukocytes to better understand the occurrence of adverse events during mechanical circulatory support.

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Antithrombotic Effects of Paeoniflorin from Paeonia suffruticosa by Selective Inhibition on Shear Stress-Induced Platelet Aggregation

International Journal of Molecular Sciences ◽

10.3390/ijms20205040 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5040 ◽

Cited By ~ 4

Author(s):

Thien Ngo ◽

Keunyoung Kim ◽

Yiying Bian ◽

Hakjun Noh ◽

Kyung-Min Lim ◽

...

Keyword(s):

Shear Stress ◽

Platelet Aggregation ◽

Ex Vivo ◽

Antiplatelet Agents ◽

Human Platelets ◽

Platelet Glycoprotein ◽

High Shear ◽

High Shear Stress ◽

Paeonia Suffruticosa ◽

Induced Aggregation

Antiplatelet agents are important in the pharmacotherapeutic regime for many cardiovascular diseases, including thrombotic disorders. However, bleeding, the most serious adverse effect associated with current antiplatelet therapy, has led to many efforts to discover novel anti-platelet drugs without bleeding issues. Of note, shear stress-induced platelet aggregation (SIPA) is a promising target to overcome bleeding since SIPA happens only in pathological conditions. Accordingly, this study was carried out to discover antiplatelet agents selectively targeting SIPA. By screening various herbal extracts, Paeonia suffruticosa and its major bioactive constituent, paeoniflorin, were identified to have significant inhibitory effects against shear-induced aggregation in human platelets. The effects of paeoniflorin on intraplatelet calcium levels, platelet degranulation, and integrin activation in high shear stress conditions were evaluated by a range of in vitro experiments using human platelets. The inhibitory effect of paeoniflorin was determined to be highly selective against SIPA, through modulating von Willebrand Factor (vWF)-platelet glycoprotein Ib (GP Ib) interaction. The effects of paeoniflorin on platelet functions under high shear stress were confirmed in the ex vivo SIPA models in rats, showing the good accordance with the anti-SIPA effects on human platelets. Treatment with paeoniflorin significantly prevented arterial thrombosis in vivo from the dose of 10 mg/kg without prolonging bleeding time or blood clotting time in rats. Collectively, our results demonstrated that paeoniflorin can be a novel anti-platelet agent selectively targeting SIPA with an improved safety profile.

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