Shear Stress‐Induced Total Blood Trauma in Multiple Species

Chan, Chris Hoi Houng; Pieper, Ina Laura; Robinson, Christian R.; Friedmann, Yael; Kanamarlapudi, Venkateswarlu; Thornton, Catherine A.

doi:10.1111/aor.12932

Cited by 57 publications

(61 citation statements)

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“…Decrease in platelet counts under shear has been noted previously as a sign of platelet activation. (8,42) This cell type was not studied further here but is the focus of ongoing work. Decreases in leukocyte counts under shear have been noted in the past in a model wherein whole blood was sheared for 10 minutes and there was a 25% decrease in leukocyte count at 60 Pa and membrane disruption at 15 Pa. (14) This is not only a longer time but a higher shear stress than in our study (~10 Pa).…”

Section: Discussionmentioning

confidence: 99%

Artificial shear stress effects on leukocytes at a biomaterial interface

et al. 2019

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Medical devices, such as ventricular assist devices (VADs), introduce both foreign materials and artificial shear stress to the circulatory system. The effects these have on leukocytes and the immune response are not well understood. Understanding how these two elements combine to affect leukocytes may reveal why some patients are susceptible to recurrent device‐related infections and provide insight into the development of pump thrombosis. Biomaterials—DLC: diamond‐like carbon‐coated stainless steel; Sap: single‐crystal sapphire; and Ti: titanium alloy (Ti6Al4V) were attached to the parallel plates of a rheometer. Whole human blood was left between the two discs for 5 minutes at +37°C with or without the application of shear stress (0 s–1 or 1000 s–1). Blood was removed and used for complete blood cell counts, flow cytometry (leukocyte activation, cell death, microparticle generation, phagocytic ability, and reactive oxygen species [ROS] production), and the production of pro‐inflammatory cytokines. L‐selectin expression on monocytes was decreased when blood was exposed to the biomaterials both with and without shear. Applying shear stress to blood on a Sap and Ti surface led to activation of neutrophils shown as decreased L‐selectin expression. Sap and Ti blunted the LPS‐stimulated macrophage migration inhibitory factor (MIF) production, most notably when sheared on Ti. The biomaterials used here have been shown to activate leukocytes in a static environment. The introduction of shear appears to exacerbate this activation. Interestingly, a widely accepted biocompatible material (Ti) utilized in many different types of devices has the capacity for immune cell activation and inhibition of MIF secretion when combined with shear stress. These findings contribute to our understanding of the contribution of biomaterials and shear stress to recurrent infections and vulnerability to sepsis in some VAD patients as well as pump thrombosis.

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Section: Discussionmentioning

confidence: 99%

Artificial shear stress effects on leukocytes at a biomaterial interface

et al. 2019

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“…Levels of pfHb obtained with ovine blood were one quarter of those obtained in bovine blood after 360 min pumping in the CentriMag at the standard condition (2.5 6 1.0 vs. 10 6 1.5 mg/dL), with mg NIH roughly one-third in ovine compared to bovine blood (0.38 6 0.15 compared to 1.10 6 0.5 mg/100 L) (13). In our previous multispecies comparison study, in which we evaluated the response to shear caused by a rheometer, we also observed greater hemolysis in bovine abattoir compared to ovine venepuncture blood at high shear (75 vs. 50 mg/dL at 8000/s, respectively), although this difference was not statistically significant (34).…”

Section: Discussionmentioning

confidence: 74%

Ovine Leukocyte Microparticles Generated by the CentriMag Ventricular Assist Device In Vitro

et al. 2018

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Ventricular assist devices (VADs) are a life-saving form of mechanical circulatory support in heart failure patients. However, VADs have not yet reached their full potential due to the associated side effects (thrombosis, bleeding, infection) related to the activation and damage of blood cells and proteins caused by mechanical stress and foreign materials. Studies of the effects of VADs on leukocytes are limited, yet leukocyte activation and damage including microparticle generation can influence both thrombosis and infection rates. Therefore, the aim was to develop a multicolor flow cytometry assessment of leukocyte microparticles (LMPs) using ovine blood and the CentriMag VAD as a model for shear stress. Ovine blood was pumped for 6 h in the CentriMag and regular samples analyzed for hemolysis, complete blood counts and LMP by flow cytometry during three different pump operating conditions (low flow, standard, high speed). The high speed condition caused significant increases in plasma-free hemoglobin; decreases in total leukocytes, granulocytes, monocytes, and platelets; increases in CD45 LMPs as well as two novel LMP populations: CD11b /HLA-DR and CD11b /HLA-DR , both of which were CD14 /CD21 . CD11b /HLA-DR LMPs appeared to respond to an increase in shear magnitude whereas the CD11b /HLA-DR LMPs significantly increased in all pumping conditions. We propose that these two populations are released from granulocytes and T cells, respectively, but further research is needed to better characterize these two populations.

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“…Our results showed that bovine blood was the most similar to human blood overall, therefore bovine blood was chosen for this study (20). Our results showed that bovine blood was the most similar to human blood overall, therefore bovine blood was chosen for this study (20).…”

Section: Preparation Of Test Bloodmentioning

confidence: 76%

“…A 20 lL aliquot of the every 120 min blood samples, along with a positive control of blood treated with 5 lM phorbol 12-myristate 13-acetate (PMA) for 60 min at room temperature, were stained with 5 lL of CAPP2A (1.0 mg/dL, an antiruminant CD41/61 antibody) (from Monoclonal Antibody Center, Washington State University), as staining and analyzing methods were explained in detail previously (12,20). Samples were acquired and analyzed using BD LSR II Flow Cytometry Cell Analyzer with FACSDiva 6.1.3 software (BD Bioscience, Oxford, UK).…”

Section: Platelet Activation Assaymentioning

confidence: 99%

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In Vitro Hemocompatibility Evaluation of Ventricular Assist Devices in Pediatric Flow Conditions: A Benchmark Study

Chan¹,

Diab

Moody³

et al. 2018

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Development of pediatric ventricular assist devices (VADs) has significantly lagged behind that of adult devices. This frustrating reality is reflected by the fact that the Berlin Heart EXCOR VAD is currently the only approved pediatric-specific device in the USA. An alternative option is an off-label use of adult continuous-flow VADs, such as HeartMate II (HMII), which inevitably causes patient-device size mismatch in small children. We sought to conduct in vitro hemocompatibility testing in a pediatric flow condition, with a specific aim to provide benchmark values for future pediatric device development. Given the aforementioned fact that both pulsatile and continuous-flow devices are being used in the pediatric population, we opted to test both types of devices in the present study. The EXCOR and HMII blood pumps were tested using bovine blood under constant hemodynamic conditions (flow rate, Q = 2.5 ± 0.25L/min; differential pressure across the pump, ΔP = 68 ± 5mm Hg). Hemolysis was measured by Harboe assay. There was a steady increase in plasma free hemoglobin during in vitro testing, with a statistically significant difference between 5 and 360 min for both EXCOR (P < 0.0001) and HMII (P < 0.001). However, the degree of an increase in plasma free hemoglobin was more significant with HMII (P < 0.001). Normalized index of hemolysis for EXCOR and HMII were 0.003 ± 0.0026g/100 L and 0.085 ± 0.0119g/100 L, respectively. There was also a steady increase in platelet activation detected by CAPP2A antibody using flow cytometry, with a statistically significant difference between 5 and 360 min for both devices (P < 0.05). The degree of an increase in platelet activation was similar between the two devices (P = 0.218). High molecular weight von Willebrand factor (HMW vWF) multimer degradation measured by immunoblotting was evident for both devices, however, it was more pronounced with the EXCOR. EXCOR blood samples from all three time points (120, 240, and 360 min) were significantly different from the baseline (5 min), whereas only 360 min samples had a significant difference from the baseline with the HMII. In conclusion, we have observed similarities and differences in hemocompatibility profiles between the EXCOR and HMII, both of which are commonly used in the pediatric population. We anticipate the benchmark values in the present study will facilitate future pediatric VAD development.

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Shear Stress‐Induced Total Blood Trauma in Multiple Species

Cited by 57 publications

References 50 publications

Artificial shear stress effects on leukocytes at a biomaterial interface

Artificial shear stress effects on leukocytes at a biomaterial interface

Ovine Leukocyte Microparticles Generated by the CentriMag Ventricular Assist Device In Vitro

In Vitro Hemocompatibility Evaluation of Ventricular Assist Devices in Pediatric Flow Conditions: A Benchmark Study

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