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

Abstract

Heart failure (HF) remains a disease of ever increasing prevalence in the modern world. Patients with end-stage HF are being referred increasingly for mechanical circulatory support (MCS). MCS can assist patients who are ineligible for transplant and stabilise eligible patients prior to transplantation. It is also used during cardiopulmonary bypass (CPB) surgery to maintain circulation whilst operating on the heart. Whilst MCS can stabilise HF 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 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 in vitro to clinical MCS 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 MCS.

Anticlogging Hemofiltration Device for Mass Collection of Circulating Tumor Cells by Ligand-Free Size Selection

“…Stress greater than 10 Pa can harm WBCs, and stress greater than 150 Pa can lead to rupture of RBCs. 57 Consequently, the current fluidic operation is a secure condition for cell separation. The cross-sectional area of the filtration column is closely associated with the formation of the filter cake and hydraulic pressure and the fluidic path.…”

Immune Cell Plasticity in Inflammation: Insights into Description and Regulation of Immune Cell Phenotypes

“…Likewise, similar to the changed flow properties during sepsis, the introduction of artificial surfaces, for example, during renal replacement therapy or due to assist devices, also poses an environment for differential targeting and activation of leukocytes. Neutrophil activation and microparticle formation thus can be commonly observed in cardiopulmonary bypass and ventricular assist devices, as shear-dependent mechanical activation and phenotype switching appear to occur in a guanine-nucleotide-exchange-factor-dependent manner [ 110 ].…”

Fluid shear stress-mediated mechanotransduction in circulating leukocytes and its defect in microvascular dysfunction

“…But at increasing shear stresses other reactions are observed; neutrophils degranulate, assume different cell shapes, and even become damaged (Dewitz et al, 1977;Dewitz et al, 1979). Neutrophils adherent to a foreign surface and exposed to fluid stress may release microparticles and undergo apoptosis (Radley et al, 2019;Shive et al, 2000). The reaction of leukocytes to fluid shear stress is multi-faceted.…”