Neutrophil dysfunction due to continuous mechanical shear exposure in mechanically assisted circulation in vitro

Sun, Wenji; Zhang, Jiafeng; Shah, Aakash; Arias, Katherin; Berk, Zachary B. K.; Griffith, Bartley P.; Wu, Zhongjun J.

doi:10.1111/aor.14068

Cited by 5 publications

(7 citation statements)

References 57 publications

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“…Our group previously reported increased levels of neutrophil activation (i.e., elevation in MAC-1 and decline in CD62L and CD162) in an in vitro circulation loop using human blood with a CentriMag pump (Abbott Inc, Chicago, IL) over time. 18 Using a Couette-type blood-shearing device, we also showed an augmentation in neutrophil activation (i.e., elevation in MAC-1 and decline in CD62L but not CD162) with increasing levels of shear stress after only 0.5 s of exposure. 19 Pieper et al found a similar trend of neutrophil activation when they used ovine blood in an in vitro loop with the CentriMag VAD to evaluate the leukocyte activation and damage caused by the pump over a 6-h circulation.…”

Section: Discussionmentioning

confidence: 59%

“…21 Previously, our in vitro study showed that the CentriMag pump caused an initial increase in neutrophil phagocytic capacity in the device-assisted circulation at 1 h followed by a subsequent decline for up to 4 h in a rotational speeddependent manner. 18 We show that in patients without a bridge device, inflammatory cytokines (IL6, IL8, and TNF-α, but not IL1) increased by POD3 and normalize after 2 weeks. Similarly, a previous study reported an elevation in TNF-α, IL6, and PMN elastase throughout the entire 12-week follow-up period.…”

Section: Discussionmentioning

confidence: 65%

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Increased phagocytosis capacity of circulating neutrophils in patients on continuous flow ventricular assist device support

Awad,

Sun,

Han

et al. 2023

Artificial Organs

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BackgroundNeutrophils take part in the innate immune response, phagocytosis, and pro‐inflammatory cytokine release. The phagocytic capacity of circulating neutrophils in patients on continuous flow (CF) ventricular assist device (VAD) has not been well studied.MethodsBlood samples from 14 patients undergoing CF‐VAD implantation were collected and analyzed preoperatively (at baseline) and on postoperative days (POD) 3, 7, 14, and 28. Flow cytometry was used to assess the surface expression levels of CD62L, CD162, and macrophage antigen‐1 (MAC‐1) and neutrophil phagocytic capacity. Interleukin 1 (IL1), IL6, IL8, TNF‐α, neutrophil elastase, and myeloperoxidase in plasma were measured using enzyme‐linked immunosorbent assays.ResultsAmong the 14 patients, seven patients had preoperative bridge device support. Relative to baseline, patients with no bridge device had elevated leukocyte count and neutrophil elastase by POD3 which normalized by POD7. Neutrophil activation level, IL6, IL8, and TNF‐α increased by POD3 and sustained elevated levels for 7–14 days postoperatively. Elevated neutrophil phagocytic capacity persisted even until POD28. Similar patterns were observed in patients on a preoperative bridge device.ConclusionsNeutrophil activation and phagocytic capacity increased in response to VAD support, while inflammatory cytokines remain elevated for up to 2 weeks postoperatively. These findings may indicate that VAD implantation elicits circulating neutrophils to an abnormal preemptive phagocytotic phenotype.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 65%

Increased phagocytosis capacity of circulating neutrophils in patients on continuous flow ventricular assist device support

Awad,

Sun,

Han

et al. 2023

Artificial Organs

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“…The few in-vitro studies that have been published show leukocyte morphological changes, reduced lifecycle, diminished cell immunity, surface receptor loss, activation, and cell fragmentation after exposure to HMSS. 7,10–12 These leukocyte alterations have also been reported in vivo in clinical studies of LVAD patients. Reduced leukocyte count, compromised cellular immunity, increased leukocyte-platelet aggregates, cellular fragmentations, microparticle generation, and leukocyte activation were reported.…”

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confidence: 62%

Neutrophil Structural and Functional Alterations After High Mechanical Shear Stress Exposure

et al. 2023

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Patients on mechanical circulatory support are prone to infections, increasing morbidity and mortality. These circulatory support devices generate high mechanical shear stress (HMSS) that can causes trauma to blood. When leukocytes become damaged, their immune response function may be impaired or weakened, leading to increased infection vulnerability. This study examined neutrophil structural and functional alterations after exposure to 75, 125, and 175 Pa HMSS for 1 second. Human blood was exposed to three levels of HMSS using a blood shearing device. Neutrophil morphological alteration was characterized by examining blood smears. Flow cytometry assays were used to analyze expression levels of CD62L and CD162 receptors, activation level (CD11b), and aggregation (platelet-neutrophil aggregates). Neutrophil phagocytosis and rolling were examined via functional assays. The results show neutrophil structure (morphology and surface receptors) and function (activation, aggregation, phagocytosis, rolling) were significantly altered after HMSS exposure. These alterations include cell membrane damage, loss of surface receptors (CD62L and CD162), initiation of activation and aggregation, upregulation of phagocytic ability and increased rolling speed. The alterations were the most severe after 175 Pa exposure. HMSS caused damage and activation of neutrophils, potentially impairing normal neutrophil function, leading to weakened immune defense and increasing a patient's vulnerability to infections.

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“…The pressure heads for three modes at the flow rate of 4.5 L/min can reach 75, 150, and 350 mmHg, respectively. 19…”

Section: Methodsmentioning

confidence: 99%

A multi-constituent model for assessing the effect of impeller shroud on the thrombosis potential of a centrifugal blood pump

Lv,

He,

Liu

et al. 2024

Int J Artif Organs

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Centrifugal blood pumps can be used for treating heart failure patients. However, pump thrombosis has remained one of the complications that trouble clinical treatment. This study analyzed the effect of impeller shroud on the thrombosis risk of the blood pump, and predicted areas prone to thrombosis. Multi-constituent transport equations were presented, considering mechanical activation and biochemical activation. It was found that activated platelets concentration can increase with shear stress and adenosine diphosphate(ADP) concentration increasing, and the highest risk of thrombosis inside the blood pump was under extracorporeal membrane oxygenation (ECMO) mode. Under the same condition, ADP concentration and thrombosis index of semi-shroud impeller can increase by 7.3% and 7.2% compared to the closed-shroud impeller. The main reason for the increase in thrombosis risk was owing to elevated scalar shear stress and more coagulation promoting factor-ADP released. The regions with higher thrombosis potential were in the center hole, top and bottom clearance. As a novelty, the findings revealed that impeller shroud can influence mechanical and biochemical activation factors. It is useful for identifying potential risk regions of thrombus formation based on relative comparisons.

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Neutrophil dysfunction due to continuous mechanical shear exposure in mechanically assisted circulation in vitro

Cited by 5 publications

References 57 publications

Increased phagocytosis capacity of circulating neutrophils in patients on continuous flow ventricular assist device support

Increased phagocytosis capacity of circulating neutrophils in patients on continuous flow ventricular assist device support

Neutrophil Structural and Functional Alterations After High Mechanical Shear Stress Exposure

A multi-constituent model for assessing the effect of impeller shroud on the thrombosis potential of a centrifugal blood pump

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