The CentriMag Centrifugal Blood Pump as a Benchmark for In Vitro Testing of Hemocompatibility in Implantable Ventricular Assist Devices

Abstract

Implantable ventricular assist devices (VADs) have proven efficient in advanced heart failure patients as a bridge-to-transplant or destination therapy. However, VAD usage often leads to infection, bleeding, and thrombosis, side effects attributable to the damage to blood cells and plasma proteins. Measuring hemolysis alone does not provide sufficient information to understand total blood damage, and research exploring the impact of currently available pumps on a wider range of blood cell types and plasma proteins such as von Willebrand factor (vWF) is required to further our understanding of safer pump design. The extracorporeal CentriMag (Thoratec Corporation, Pleasanton, CA, USA) has a hemolysis profile within published standards of normalized index of hemolysis levels of less than 0.01 g/100 L at 100 mm Hg but the effect on leukocytes, vWF multimers, and platelets is unknown. Here, the CentriMag was tested using bovine blood (n = 15) under constant hemodynamic conditions in comparison with a static control for total blood cell counts, hemolysis, leukocyte death, vWF multimers, microparticles, platelet activation, and apoptosis. The CentriMag decreased the levels of healthy leukocytes (P < 0.006), induced leukocyte microparticles (P < 10−5), and the level of high molecular weight of vWF multimers was significantly reduced in the CentriMag (P < 10−5) all compared with the static treatment after 6 h in vitro testing. Despite the leukocyte damage, microparticle formation, and cleavage of vWF multimers, these results show that the CentriMag is a hemocompatible pump which could be used as a standard in blood damage assays to inform the design of new implantable blood pumps.

Roller and Centrifugal Pumps

“…41 In fact, the CentriMag pump has been shown to significantly reduce high-molecular-weight vWF after 3 hours in a recirculating in vitro test loop. 42 Centrifugal and roller pumps generate flow by different mechanisms. Roller pumps produce peristaltic flow by displacement of fluid from an occlusive rotor applied against a compressible tube.…”

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

“…The plasma free hemoglobin (pfHb) was measured using a UV/visible spectrophotometer (SmartSpec plus, Bio-Rad, Hercules, CA, USA) and normalized index of hemolysis (NIH) was calculated as previously (12,21,22). The plasma free hemoglobin (pfHb) was measured using a UV/visible spectrophotometer (SmartSpec plus, Bio-Rad, Hercules, CA, USA) and normalized index of hemolysis (NIH) was calculated as previously (12,21,22).…”

“…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).…”

“…To provide an in vitro benchmark data for adult device development, we previously tested the CentriMag blood pump (St. Jude Medical Inc., St. Paul, MN, USA) (12); in this study, pump flow rate and differential pressure across the pump were set at adult conditions (Q 5 5 6 0.25 L/min; DP 5 100 6 3 mm Hg) according to the standard practice for assessment of blood damage in continuous flow blood pumps-American Society for Testing and Materials (ASTM) (13,14). This should help VAD developers to recognize the potential need for design iterations without delay.…”

Modelagem matemática da fluidodinâmica não-newtoniana e bifásica simplificada da hemólise induzida mecanicamente em sistemas de bombeamento centrífugo de sangue

“…No entanto, tais investigações experimentais demandam tempo e recursos financeiros, tendo em vista que cada modificação de projeto requer adaptações, ajustes e por vezes, a construção de novos dispositivos, peças ou componentes. Além disso, a aplicação de resultados de experimentos in vitro em situações in vivo não é trivial (Chan et al, 2015), (Sakota et al, 2015), no sentido de que estas última oferecem uma complexidade maior. Dentro deste contexto, as técnicas de modelagem matemática e simulações computacionais aliadas às facilidades para virtualização e ampliação em tempo real dos dispositivos e procedimentos médicos desdobram um ambiente completo para condução de experimentos in silico, sem limitações (Baillargeon et al, 2015).…”