Infection, Oxidative Stress, and Changes in Circulating Regulatory T Cells of Heart Failure Patients Supported by Continuous-Flow Ventricular Assist Devices

Mondal, Nandan K.; Sobieski, Michael A.; Pham, Si M.; Griffith, Bartley P.; Koenig, Steven C.; Slaughter, Mark S.; Wu, Zhongjun J.

doi:10.1097/mat.0000000000000487

Cited by 16 publications

(17 citation statements)

References 29 publications

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“…The one available study showed increased apoptotic activity in CD4 + T cells up to 4 weeks post-operatively which normalised to baseline after 7 weeks (45) rather than sustained excessive CD4+ T cell apoptosis linked to a drastic reduction in circulating CD4+ T cells in pulsatile devices (20). More recently, a study of infection rates in continuous flow VAD (CF-VAD) patients found that patients with infection had much higher numbers of circulating regulatory T (Treg) cells than those without infection (46). Oxidative stress was also prominent in CF-VAD patients and combined with increased Treg cells could lead to immunosuppression and pathogen persistence (46).…”

Section: Vad Use Can Lead To Immunosuppressionmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Vad Use Can Lead To Immunosuppressionmentioning

confidence: 99%

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

et al. 2018

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“…Lymphocytes are affected by both pulsatile and CF-VADs [13][14][15]. A general lymphopenia occurred in patients, implanted with the early pulsatile HeartMate XVE [14].…”

Section: Leukocytesmentioning

confidence: 99%

“…Patients with CF-VADs also have changes in their T cell levels. However, contrary to pulsatile LVAD-patients, those implanted with CF-VADs (specific device not published) and who suffered from infection had significantly higher levels of CD4+/CD25+ Tregs and increased lymphocyte reactive oxygen species (ROS) compared to VAD-patients without infection [13]. Whether these differences between pulsatile and CF VADs relates to pulsatility would be an interesting topic for further studies.…”

Section: Leukocytesmentioning

confidence: 99%

“…As our group has shown, vWF degradation caused by shear stress in vitro can be assessed using flow cytometry a flow cytometry-based ristocetin assay [37]. However, it appears as if T cells could be another missing link needed to describe the effects of non-pulsatile [13] and pulsatile [14,15] flow on the blood. Therefore, we propose that assays for T-cells are established for sheep and cow blood in order to study the effects of pulsatility, in order to gather more scientific evidence that could be used to interpret the clinical data.…”

Section: Leukocytesmentioning

confidence: 99%

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Multidimensional Flow Cytometry for Testing Blood-Handling Medical Devices

Pieper¹,

Radley²,

Thornton³

2018

Multidimensional Flow Cytometry Techniques for Novel Highly Informative Assays

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Blood handling devices such as left ventricular assist devices and total artificial hearts offer life-saving treatments for patients suffering from severe heart failure. Current devices have clinically proven that heart assist pumps are a safe and effective therapy, and indeed in many cases they are the only available method of treatment. However, current devices cause side effects including stroke, bleeding, infection, and thrombosis, preventing the technology from reaching its full potential. If the side effects could be reduced, then more patients could benefit from these devices. The complications are related to damage to blood cells and proteins as a result of contact with foreign materials and mechanical stress. There is a need for better devices with minimal blood impact to enable more patients to be safely treated; better tools, especially flow cytometry, could support the device development life cycle. In this chapter we review the clinical, in vivo, and in vitro flow cytometry data available for ventricular assist devices, conduct a gap analysis, and identify areas of future possibilities for device developers to establish new flow cytometry-based methodologies.

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“…Non-physiological high shear stress has been suggested to contribute to the shedding of key platelet receptors [17–19]. Studies also reported that oxidative stress may also influence the alteration of platelet and leukocyte functionality in CF-LAVD patients with systemic inflammation, infection and sepsis [20,21]. Oxidative stress and peroxide synthesized in the platelet lipoxygenase pathway activates tumor necrosis factor-alpha-converting enzyme and induce shedding of key platelet receptors in murine and human model [22].…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress induced modulation of platelet integrin α2bβ3 expression and shedding may predict the risk of major bleeding in heart failure patients supported by continuous flow left ventricular assist devices

Mondal

Chen

Trivedi

et al. 2017

Thrombosis Research

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Introduction Oxidative stress and platelet integrin α2bβ3 plays important role in the process of hemostasis and thrombosis. We hypothesized that device-induced patient specific oxidative stress and integrin α2bβ3 shedding may be linked to major bleeding complication (MBC) in heart failure (HF) patients supported by continuous flow left ventricular assist devices (CF-LVADs). Materials and Methods We recruited 47 patients implanted with CF-LVADs and 15 healthy volunteers. Fourteen patients developed MBC (bleeder group) within one month after implantation while others were considered non-bleeder group (n=33). Oxidative stresses were evaluated by measuring reactive oxygen species (ROS) in platelets, superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) and oxidized low density lipoprotein (oxLDL). Assessments of α2bβ3 were carried out using flow cytometry and ELISA. Results Biomarkers of oxidative stress and α2bβ3 shedding (decreased surface expression and higher plasma levels) were found to be preexisting condition in all HF patients prior to CF-LVAD implantation compared to the healthy volunteers. Significantly elevated levels of ROS and oxLDL; concomitant depletion of SOD and TAC; and α2bβ3 shedding were observed in the bleeder group temporarily in comparison to the non-bleeder group after CF-LVAD implantation. A significantly strong association between α2bβ3 shedding and biomarkers of oxidative stress was observed; suggesting a potential role of oxidative stress in platelet integrin shedding leading to MBC after CF-LVAD implantation. Moreover, a receiver operating characteristic (ROC) analysis indicated that the likelihood of MBC data from Integrin α2bβ3 shedding had a predictive power of MBC in CF-LVAD patients. Conclusions Oxidative stress might play a potential role in accelerating α2bβ3 shedding and platelet dysfunction, resulting in MBC in CF-LVAD patients. Integrin α2bβ3 shedding may be used to refine bleeding risk stratification in CF-LVAD patients.

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Infection, Oxidative Stress, and Changes in Circulating Regulatory T Cells of Heart Failure Patients Supported by Continuous-Flow Ventricular Assist Devices

Cited by 16 publications

References 29 publications

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

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

Multidimensional Flow Cytometry for Testing Blood-Handling Medical Devices

Oxidative stress induced modulation of platelet integrin α2bβ3 expression and shedding may predict the risk of major bleeding in heart failure patients supported by continuous flow left ventricular assist devices

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