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Papers by katherin arias

Research paper thumbnail of Neutrophil Structural and Functional Alterations After High Mechanical Shear Stress Exposure

Research paper thumbnail of Acquired platelet defects are responsible for nonsurgical bleeding in left ventricular assist device recipients

Artificial Organs

BackgroundLeft ventricular assist devices (LVADs) have been used as a standard treatment option f... more BackgroundLeft ventricular assist devices (LVADs) have been used as a standard treatment option for patients with advanced heart failure. However, these devices are prone to adverse events. Nonsurgical bleeding (NSB) is the most common complication in patients with continuous flow (CF) LVADs. The development of acquired von Willebrand syndrome (AVWS) in CF‐LVAD recipients is thought to be a key factor. However, AVWS is seen across a majority of LVAD patients, not just those with NSB. The purpose of this study was to examine the link between acquired platelet defects and NSB in CF‐LVAD patients.MethodsBlood samples were collected from 62 CF‐LVAD patients at pre‐ and 4 post‐implantation timepoints. Reduced adhesion receptor expression (GPIbα and GPVI) and activation of platelets (GPIIb/IIIa activation) were used as markers for acquired platelet defects.ResultsTwenty‐three patients experienced at least one NSB episode. Significantly higher levels of platelet activation and receptor red...

Research paper thumbnail of El análisis de artefactos como estrategia didáctica para el desarrollo de competencias de diseño en estudiantes con discapacidad visual adquirida

Este trabajo se encarga de replicar una investigacion realizada en el 2010 con el fin de retomar ... more Este trabajo se encarga de replicar una investigacion realizada en el 2010 con el fin de retomar la anterior investigacion con los mismos instrumentos, la misma metodologia de investigacion, las mismas actividades, en donde lo unico que se cambia es la poblacion de estudio, esta investigacion muestra una propuesta que se toma desde la estrategia didactica de analisis de artefactos para indagar el desarrollo de las competencias de diseno en personas con discapacidad visual adquirida, ademas de comprobar, validar y comparar la propuesta realizada por Perez 2010. Esta investigacion se realiza con el desarrollo de 4 fases de trabajo y a traves de diferentes actividades tecnologicas escolares que permiten la identificacion y analisis de artefactos.

Research paper thumbnail of Neutrophil dysfunction due to continuous mechanical shear exposure in mechanically assisted circulation in vitro

Artificial Organs, 2021

ObjectiveLeukocytes play an important role in the body's immune system. The aim of this study... more ObjectiveLeukocytes play an important role in the body's immune system. The aim of this study was to assess alterations in neutrophil phenotype and function in pump‐assisted circulation in vitro.MethodsHuman blood was circulated for four hours in three circulatory flow loops with a CentriMag blood pump operated at a flow of 4.5 L/min at three rotational speeds (2100, 2800, and 4000 rpm), against three pressure heads (75, 150, and 350 mm Hg), respectively. Blood samples were collected hourly for analyses of neutrophil activation state (Mac‐1, CD62L, CD162), neutrophil reactive oxygen species (ROS) production, apoptosis, and neutrophil phagocytosis.ResultsActivated neutrophils indicated by both Mac‐1 expression and decreased surface expression of CD62L and CD162 receptors increased with time in three loops. The highest level of neutrophil activation was observed in the loop with the highest rotational speed. Platelet‐neutrophil aggregates (PNAs) progressively increased in two loop...

Research paper thumbnail of Impact of high mechanical shear stress and oxygenator membrane surface on blood damage relevant to thrombosis and bleeding in a pediatric ECMO circuit

Artificial Organs, 2020

Objective: The roles of the large membrane surface of the oxygenator and the high mechanical shea... more Objective: The roles of the large membrane surface of the oxygenator and the high mechanical shear stress (HMSS) of the pump in the ECMO circuit were examined under a pediatric support setting. Methods: A clinical centrifugal pump and a pediatric oxygenator were used to construct the ECMO circuit. An identical circuit without the oxygenator was constructed for comparison. Fresh human blood was circulated in the two circuits for 4 hours under the identical pump speed and flow. Blood samples were collected hourly for blood damage assessment, including platelet activation, generation of platelet-derived microparticles (PDMP), losses of key platelet hemostasis receptors (glycoprotein (GP) Ibα (GPIbα) and GPVI) and high molecular weight multimers (HMWM) of von Willebrand factor (VWF) and plasma free hemoglobin (PFH). Platelet adhesion on fibrinogen, VWF and collagen was further examined. Results: The levels of platelet activation and generation of PDMP and PFH exhibited an increasing trend with circulation time while the expression levels of GPIbα and GPVI receptors on the platelet surface decreased. Correspondingly, the platelets in the blood samples exhibited increased adhesion capacity to fibrinogen and decreased adhesion capacities on VWF and collagen with circulation time. Loss of HMWM of VWF occurred in both circuits. No statistically significant differences were found in all the measured parameters for blood damage and platelet adhesion function between the two circuits. Conclusions: The results indicate that HMSS from the pump played a dominant role in blood damage associated with ECMO and the impact of the large surface of the oxygenator on blood damage was insignificant.

Research paper thumbnail of Direct current stimulation of endothelial monolayers induces a transient and reversible increase in transport due to the electroosmotic effect

Scientific Reports, 2018

We investigated the effects of direct current stimulation (DCS) on fluid and solute transport acr... more We investigated the effects of direct current stimulation (DCS) on fluid and solute transport across endothelial cell (EC) monolayers in vitro. Our motivation was transcranial direct current stimulation (tDCS) that has been investigated for treatment of neuropsychiatric disorders, to enhance neurorehabilitation, and to change cognition in healthy subjects. The mechanisms underlying this diversity of applications remain under investigation. To address the possible role of blood-brain barrier (BBB) changes during tDCS, we applied direct current to cultured EC monolayers in a specially designed chamber that generated spatially uniform direct current. DCS induced fluid and solute movement across EC layers that persisted only for the duration of the stimulation suggesting an electroosmosis mechanism. The direction of induced transport reversed with DCS polarity – a hallmark of the electroosmotic effect. The magnitude of DCS-induced flow was linearly correlated to the magnitude of the app...

Research paper thumbnail of The Role of a Disintegrin and Metalloproteinase Proteolysis and Mechanical Damage in Nonphysiological Shear Stress-Induced Platelet Receptor Shedding

ASAIO Journal, 2019

In order to explore the role of a disintegrin and metalloproteinase (ADAM) proteolysis and direct... more In order to explore the role of a disintegrin and metalloproteinase (ADAM) proteolysis and direct mechanical damage in non-physiologic shear stress (NPSS)-caused platelet receptor shedding, the healthy donor blood treated with/without ADAM inhibitor was exposed to NPSS (150 Pa). The expression of the platelet surface receptors glycoprotein (GP) Ibα and GPVI in NPSS-damaged blood was quantified with flow cytometry. The impact of ADAM inhibition on adhesion of NPSS-damaged platelets on von Willibrand factor (VWF) and collagen was explored with fluorescence microscopy. The impact of ADAM inhibition on ristocetin-and collagen-caused aggregation of NPSS-damaged platelets was examined by aggregometry. The results showed that ADAM inhibition could lessen the NPSSinduced loss of platelet surface receptor GPIbα (12%) and GPVI (9%), moderately preserve adhesion of platelets on VWF (7.4%) and collagen (8.4%), and partially restore the aggregation of NPSS-sheared platelets induced by ristocetin (18.6 AU*min) and collagen (48.2 AU*min). These results indicated that ADAM proteolysis played a role in NPSS-induced receptor shedding. However, the ADAM inhibition couldn't completely suppress the NPSS-caused loss of the platelet surface receptors (GPIbα and GPVI), only partially prevented the NPSS-induced reduction of platelet adhesion to VWF and collagen, and the agonist (ristocetin and collagen)-caused platelet aggregation. These results suggested that the direct mechanical damage is partially responsible for NPSS-induced receptor shedding in addition to the ADAM proteolysis. In conclusion, NPSS relevant to blood contacting medical devices can induce ADAM proteolysis and direct mechanical damage on the platelet receptor GPIbα and GPVI, leading to comprised hemostasis.

Research paper thumbnail of Device‐induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding

Artificial Organs, 2019

Thrombotic and bleeding complications are the major obstacles for expanding mechanical circulator... more Thrombotic and bleeding complications are the major obstacles for expanding mechanical circulatory support (MCS) beyond the current use. While providing the needed hemodynamic support, those devices can induce damage to blood, particularly to platelets. In this study, we investigated device‐induced alteration of three major platelet surface receptors, von Willebrand factor (VWF) and associated hemostatic functions relevant to thrombosis and bleeding. Fresh human whole blood was circulated in an extracorporeal circuit with a clinical rotary blood pump (CentriMag, Abbott, Chicago, IL, USA) under the clinically relevant operating condition for 4 hours. Blood samples were examined every hour for glycoprotein (GP) IIb/IIIa activation and receptor loss of GPVI and GPIbα on the platelet surface with flow cytometry. Soluble P‐selectin in hourly collected blood samples was measured by enzyme linked immunosorbent assay to characterize platelet activation. Adhesion of device‐injured platelets ...

Research paper thumbnail of Neutrophil injury and function alterations induced by high mechanical shear stress with short exposure time

Artificial Organs, 2020

High mechanical shear stresses (HMSS) can cause damage to blood, which manifests as morphologic c... more High mechanical shear stresses (HMSS) can cause damage to blood, which manifests as morphologic changes, shortened life span, biochemical alterations, and complete rupture of blood cells and proteins, leading to the alterations of normal blood function. The aim of this study is to determine the state of neutrophil activation and function alterations caused by HMSS with short exposure time relevant to ventricular assist devices. Blood from healthy donors was exposed to three levels of HMSS (75Pa, 125Pa, and 175Pa) for a short exposure time (0.5 s) using our Couette‐type blood‐shearing device. Neutrophil activation (Mac‐1, platelet‐neutrophil aggregates) and surface expression levels of two key functional receptors (CD62L and CD162) on neutrophils were evaluated by flow cytometry. Neutrophil phagocytosis and transmigration were also examined with functional assays. Results showed that the expression of Mac‐1 on neutrophils and platelet‐neutrophil aggregates increased significantly whi...

Research paper thumbnail of Neutrophil Structural and Functional Alterations After High Mechanical Shear Stress Exposure

Research paper thumbnail of Acquired platelet defects are responsible for nonsurgical bleeding in left ventricular assist device recipients

Artificial Organs

BackgroundLeft ventricular assist devices (LVADs) have been used as a standard treatment option f... more BackgroundLeft ventricular assist devices (LVADs) have been used as a standard treatment option for patients with advanced heart failure. However, these devices are prone to adverse events. Nonsurgical bleeding (NSB) is the most common complication in patients with continuous flow (CF) LVADs. The development of acquired von Willebrand syndrome (AVWS) in CF‐LVAD recipients is thought to be a key factor. However, AVWS is seen across a majority of LVAD patients, not just those with NSB. The purpose of this study was to examine the link between acquired platelet defects and NSB in CF‐LVAD patients.MethodsBlood samples were collected from 62 CF‐LVAD patients at pre‐ and 4 post‐implantation timepoints. Reduced adhesion receptor expression (GPIbα and GPVI) and activation of platelets (GPIIb/IIIa activation) were used as markers for acquired platelet defects.ResultsTwenty‐three patients experienced at least one NSB episode. Significantly higher levels of platelet activation and receptor red...

Research paper thumbnail of El análisis de artefactos como estrategia didáctica para el desarrollo de competencias de diseño en estudiantes con discapacidad visual adquirida

Este trabajo se encarga de replicar una investigacion realizada en el 2010 con el fin de retomar ... more Este trabajo se encarga de replicar una investigacion realizada en el 2010 con el fin de retomar la anterior investigacion con los mismos instrumentos, la misma metodologia de investigacion, las mismas actividades, en donde lo unico que se cambia es la poblacion de estudio, esta investigacion muestra una propuesta que se toma desde la estrategia didactica de analisis de artefactos para indagar el desarrollo de las competencias de diseno en personas con discapacidad visual adquirida, ademas de comprobar, validar y comparar la propuesta realizada por Perez 2010. Esta investigacion se realiza con el desarrollo de 4 fases de trabajo y a traves de diferentes actividades tecnologicas escolares que permiten la identificacion y analisis de artefactos.

Research paper thumbnail of Neutrophil dysfunction due to continuous mechanical shear exposure in mechanically assisted circulation in vitro

Artificial Organs, 2021

ObjectiveLeukocytes play an important role in the body's immune system. The aim of this study... more ObjectiveLeukocytes play an important role in the body's immune system. The aim of this study was to assess alterations in neutrophil phenotype and function in pump‐assisted circulation in vitro.MethodsHuman blood was circulated for four hours in three circulatory flow loops with a CentriMag blood pump operated at a flow of 4.5 L/min at three rotational speeds (2100, 2800, and 4000 rpm), against three pressure heads (75, 150, and 350 mm Hg), respectively. Blood samples were collected hourly for analyses of neutrophil activation state (Mac‐1, CD62L, CD162), neutrophil reactive oxygen species (ROS) production, apoptosis, and neutrophil phagocytosis.ResultsActivated neutrophils indicated by both Mac‐1 expression and decreased surface expression of CD62L and CD162 receptors increased with time in three loops. The highest level of neutrophil activation was observed in the loop with the highest rotational speed. Platelet‐neutrophil aggregates (PNAs) progressively increased in two loop...

Research paper thumbnail of Impact of high mechanical shear stress and oxygenator membrane surface on blood damage relevant to thrombosis and bleeding in a pediatric ECMO circuit

Artificial Organs, 2020

Objective: The roles of the large membrane surface of the oxygenator and the high mechanical shea... more Objective: The roles of the large membrane surface of the oxygenator and the high mechanical shear stress (HMSS) of the pump in the ECMO circuit were examined under a pediatric support setting. Methods: A clinical centrifugal pump and a pediatric oxygenator were used to construct the ECMO circuit. An identical circuit without the oxygenator was constructed for comparison. Fresh human blood was circulated in the two circuits for 4 hours under the identical pump speed and flow. Blood samples were collected hourly for blood damage assessment, including platelet activation, generation of platelet-derived microparticles (PDMP), losses of key platelet hemostasis receptors (glycoprotein (GP) Ibα (GPIbα) and GPVI) and high molecular weight multimers (HMWM) of von Willebrand factor (VWF) and plasma free hemoglobin (PFH). Platelet adhesion on fibrinogen, VWF and collagen was further examined. Results: The levels of platelet activation and generation of PDMP and PFH exhibited an increasing trend with circulation time while the expression levels of GPIbα and GPVI receptors on the platelet surface decreased. Correspondingly, the platelets in the blood samples exhibited increased adhesion capacity to fibrinogen and decreased adhesion capacities on VWF and collagen with circulation time. Loss of HMWM of VWF occurred in both circuits. No statistically significant differences were found in all the measured parameters for blood damage and platelet adhesion function between the two circuits. Conclusions: The results indicate that HMSS from the pump played a dominant role in blood damage associated with ECMO and the impact of the large surface of the oxygenator on blood damage was insignificant.

Research paper thumbnail of Direct current stimulation of endothelial monolayers induces a transient and reversible increase in transport due to the electroosmotic effect

Scientific Reports, 2018

We investigated the effects of direct current stimulation (DCS) on fluid and solute transport acr... more We investigated the effects of direct current stimulation (DCS) on fluid and solute transport across endothelial cell (EC) monolayers in vitro. Our motivation was transcranial direct current stimulation (tDCS) that has been investigated for treatment of neuropsychiatric disorders, to enhance neurorehabilitation, and to change cognition in healthy subjects. The mechanisms underlying this diversity of applications remain under investigation. To address the possible role of blood-brain barrier (BBB) changes during tDCS, we applied direct current to cultured EC monolayers in a specially designed chamber that generated spatially uniform direct current. DCS induced fluid and solute movement across EC layers that persisted only for the duration of the stimulation suggesting an electroosmosis mechanism. The direction of induced transport reversed with DCS polarity – a hallmark of the electroosmotic effect. The magnitude of DCS-induced flow was linearly correlated to the magnitude of the app...

Research paper thumbnail of The Role of a Disintegrin and Metalloproteinase Proteolysis and Mechanical Damage in Nonphysiological Shear Stress-Induced Platelet Receptor Shedding

ASAIO Journal, 2019

In order to explore the role of a disintegrin and metalloproteinase (ADAM) proteolysis and direct... more In order to explore the role of a disintegrin and metalloproteinase (ADAM) proteolysis and direct mechanical damage in non-physiologic shear stress (NPSS)-caused platelet receptor shedding, the healthy donor blood treated with/without ADAM inhibitor was exposed to NPSS (150 Pa). The expression of the platelet surface receptors glycoprotein (GP) Ibα and GPVI in NPSS-damaged blood was quantified with flow cytometry. The impact of ADAM inhibition on adhesion of NPSS-damaged platelets on von Willibrand factor (VWF) and collagen was explored with fluorescence microscopy. The impact of ADAM inhibition on ristocetin-and collagen-caused aggregation of NPSS-damaged platelets was examined by aggregometry. The results showed that ADAM inhibition could lessen the NPSSinduced loss of platelet surface receptor GPIbα (12%) and GPVI (9%), moderately preserve adhesion of platelets on VWF (7.4%) and collagen (8.4%), and partially restore the aggregation of NPSS-sheared platelets induced by ristocetin (18.6 AU*min) and collagen (48.2 AU*min). These results indicated that ADAM proteolysis played a role in NPSS-induced receptor shedding. However, the ADAM inhibition couldn't completely suppress the NPSS-caused loss of the platelet surface receptors (GPIbα and GPVI), only partially prevented the NPSS-induced reduction of platelet adhesion to VWF and collagen, and the agonist (ristocetin and collagen)-caused platelet aggregation. These results suggested that the direct mechanical damage is partially responsible for NPSS-induced receptor shedding in addition to the ADAM proteolysis. In conclusion, NPSS relevant to blood contacting medical devices can induce ADAM proteolysis and direct mechanical damage on the platelet receptor GPIbα and GPVI, leading to comprised hemostasis.

Research paper thumbnail of Device‐induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding

Artificial Organs, 2019

Thrombotic and bleeding complications are the major obstacles for expanding mechanical circulator... more Thrombotic and bleeding complications are the major obstacles for expanding mechanical circulatory support (MCS) beyond the current use. While providing the needed hemodynamic support, those devices can induce damage to blood, particularly to platelets. In this study, we investigated device‐induced alteration of three major platelet surface receptors, von Willebrand factor (VWF) and associated hemostatic functions relevant to thrombosis and bleeding. Fresh human whole blood was circulated in an extracorporeal circuit with a clinical rotary blood pump (CentriMag, Abbott, Chicago, IL, USA) under the clinically relevant operating condition for 4 hours. Blood samples were examined every hour for glycoprotein (GP) IIb/IIIa activation and receptor loss of GPVI and GPIbα on the platelet surface with flow cytometry. Soluble P‐selectin in hourly collected blood samples was measured by enzyme linked immunosorbent assay to characterize platelet activation. Adhesion of device‐injured platelets ...

Research paper thumbnail of Neutrophil injury and function alterations induced by high mechanical shear stress with short exposure time

Artificial Organs, 2020

High mechanical shear stresses (HMSS) can cause damage to blood, which manifests as morphologic c... more High mechanical shear stresses (HMSS) can cause damage to blood, which manifests as morphologic changes, shortened life span, biochemical alterations, and complete rupture of blood cells and proteins, leading to the alterations of normal blood function. The aim of this study is to determine the state of neutrophil activation and function alterations caused by HMSS with short exposure time relevant to ventricular assist devices. Blood from healthy donors was exposed to three levels of HMSS (75Pa, 125Pa, and 175Pa) for a short exposure time (0.5 s) using our Couette‐type blood‐shearing device. Neutrophil activation (Mac‐1, platelet‐neutrophil aggregates) and surface expression levels of two key functional receptors (CD62L and CD162) on neutrophils were evaluated by flow cytometry. Neutrophil phagocytosis and transmigration were also examined with functional assays. Results showed that the expression of Mac‐1 on neutrophils and platelet‐neutrophil aggregates increased significantly whi...