PMID- 31876310 OWN - NLM STAT- MEDLINE DCOM- 20210304 LR - 20210320 IS - 1525-1594 (Electronic) IS - 0160-564X (Print) IS - 0160-564X (Linking) VI - 44 IP - 6 DP - 2020 Jun TI - Circulatory loop design and components introduce artifacts impacting in vitro evaluation of ventricular assist device thrombogenicity: A call for caution. PG - E226-E237 LID - 10.1111/aor.13626 [doi] AB - Mechanical circulatory support (MCS) devices continue to be hampered by thrombotic adverse events (AEs), a consequence of device-imparted supraphysiologic shear stresses, leading to shear-mediated platelet activation (SMPA). In advancing MCS devices from design to clinical use, in vitro circulatory loops containing the device under development and testing are utilized as a means of assessing device thrombogenicity. Physical characteristics of these test circulatory loops may also contribute to inadvertent platelet activation through imparted shear stress, adding inadvertent error in evaluating MCS device thrombogenicity. While investigators normally control for the effect of a loop, inadvertent addition of what are considered innocuous connectors may impact test results. Here, we tested the effect of common, additive components of in vitro circulatory test loops, that is, connectors and loop geometry, as to their additive contribution to shear stress via both in silico and in vitro models. A series of test circulatory loops containing a ventricular assist device (VAD) with differing constituent components, were established in silico including: loops with 0~5 Luer connectors, a loop with a T-connector creating 90 degrees angulation, and a loop with 90 degrees angulation. Computational fluid dynamics (CFD) simulations were performed using a k - omega shear stress transport turbulence model to platelet activation index (PAI) based on a power law model. VAD-operated loops replicating in silico designs were assembled in vitro and gel-filtered human platelets were recirculated within (1 hour) and SMPA was determined. CFD simulations demonstrated high shear being introduced at non-smooth regions such as edge-connector boundaries, tubing, and at Luer holes. Noticeable peaks' shifts of scalar shear stress (sss) distributions toward high shear-region existed with increasing loop complexity. Platelet activation also increased with increasing shear exposure time, being statistically higher when platelets were exposed to connector-employed loop designs. The extent of platelet activation in vitro could be successfully predicted by CFD simulations. Loops employing additional components (non-physiological flow pattern connectors) resulted in higher PAI. Loops with more components (5-connector loop and 90 degrees T-connector) showed 63% and 128% higher platelet activation levels, respectively, versus those with fewer (0-connector (P = .023) and a 90 degrees heat-bend loop (P = .0041). Our results underscore the importance of careful consideration of all component elements, and suggest the need for standardization in designing in vitro circulatory loops for MCS device evaluation to avoid inadvertent additive SMPA during device evaluation, confounding overall results. Specifically, we caution on the use and inadvertent introduction of additional connectors, ports, and other shear-generating elements which introduce artifact, clouding primary device evaluation via introduction of additive SMPA. CI - (c) 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. FAU - Li, Mengtang AU - Li M AUID- ORCID: 0000-0002-3594-4808 AD - Department of Mechanical Engineering, Vanderbilt University, Nashville, TN, USA. FAU - Walk, Ryan AU - Walk R AD - Department of Medicine, Sarver Heart Center, University of Arizona, Tucson, AZ, USA. FAU - Roka-Moiia, Yana AU - Roka-Moiia Y AD - Department of Medicine, Sarver Heart Center, University of Arizona, Tucson, AZ, USA. FAU - Sheriff, Jawaad AU - Sheriff J AUID- ORCID: 0000-0002-1297-0739 AD - Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA. FAU - Bluestein, Danny AU - Bluestein D AD - Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA. FAU - Barth, Eric J AU - Barth EJ AD - Department of Mechanical Engineering, Vanderbilt University, Nashville, TN, USA. FAU - Slepian, Marvin J AU - Slepian MJ AUID- ORCID: 0000-0002-7864-6691 AD - Department of Medicine, Sarver Heart Center, University of Arizona, Tucson, AZ, USA. AD - Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA. AD - Department of Biomedical Engineering, University of Arizona, Tucson, AZ, USA. LA - eng GR - U01 HL131052/HL/NHLBI NIH HHS/United States GR - U01 1U01HL131052-01A1/NH/NIH HHS/United States PT - Journal Article DEP - 20200129 PL - United States TA - Artif Organs JT - Artificial organs JID - 7802778 SB - IM MH - Adult MH - Artifacts MH - Blood Platelets/physiology MH - Computer Simulation MH - *Equipment Design MH - Healthy Volunteers MH - Heart-Assist Devices/*adverse effects MH - Hemodynamics/*physiology MH - Humans MH - Platelet Activation/physiology MH - Shear Strength MH - Stress, Mechanical MH - Thrombosis/etiology/*prevention & control PMC - PMC7972931 MID - NIHMS1678973 OTO - NOTNLM OT - computational fluid dynamics OT - mock circulatory loop OT - platelet activation OT - shear stress OT - shear-mediated platelet activation OT - thrombogenicity OT - ventricular assist device EDAT- 2019/12/27 06:00 MHDA- 2021/03/05 06:00 PMCR- 2021/03/19 CRDT- 2019/12/27 06:00 PHST- 2019/09/12 00:00 [received] PHST- 2019/11/20 00:00 [revised] PHST- 2019/12/16 00:00 [accepted] PHST- 2019/12/27 06:00 [pubmed] PHST- 2021/03/05 06:00 [medline] PHST- 2019/12/27 06:00 [entrez] PHST- 2021/03/19 00:00 [pmc-release] AID - 10.1111/aor.13626 [doi] PST - ppublish SO - Artif Organs. 2020 Jun;44(6):E226-E237. doi: 10.1111/aor.13626. Epub 2020 Jan 29.