title: Preclinical Models for Translational Investigations of Left Ventricular Assist Device-Associated von Willebrand Factor Degradation.
abstract: Evidence suggests a major role for von Willebrand factor (vWF) in left ventricular assist device (LVAD)-associated bleeding. However, the mechanisms of vWF degradation during LVAD support are not well understood. We developed: (i) a simple and inexpensive vortexer model; and (ii) a translational LVAD mock circulatory loop to perform preclinical investigations of LVAD-associated vWF degradation. Whole blood was obtained from LVAD patients (n = 8) and normal humans (n = 15). Experimental groups included: (i) blood from continuous-flow LVAD patients (baseline vs. post-LVAD, n = 8); (ii) blood from normal humans (baseline vs. 4 h in vitro laboratory vortexer, ∼ 2400 rpm, shear stress ∼175 dyne/cm(2) , n = 8); and (iii) blood from normal humans (baseline vs. 12 h HeartMate II mock circulatory loop, 10 000 rpm, n = 7). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblotting. Blood from LVAD patients, blood exposed to in vitro supraphysiologic shear stress, and blood circulated through an LVAD mock circulatory loop demonstrated a similar profile of decreased large vWF multimers and increased vWF degradation fragments. A laboratory vortexer and an LVAD mock circulatory loop reproduced the pathologic degradation of vWF that occurs during LVAD support. Both models are appropriate for preclinical studies of LVAD-associated vWF degradation.
authors: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors: David J
authors: DJ
authors: Restle
authors: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors: David M
authors: DM
authors: Zhang
authors: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors: George
authors: G
authors: Hung
authors: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors: Jessica L
authors: JL
authors: Howard
authors: Thoratec Corporation, Pleasanton, CA, USA.
authors: Faouzi
authors: F
authors: Kallel
authors: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors: Michael A
authors: MA
authors: Acker
authors: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors: Pavan
authors: P
authors: Atluri
authors: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors: Carlo R
authors: CR
authors: Bartoli
mesh_terms: D006353:Heart-Assist Devices / Q000009:adverse effects*; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D055503:Protein Multimerization; D059748:Proteolysis; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor
keywords: Bleeding; Blood trauma; Heart failure; Left ventricular assist device; Mechanical circulatory support; Shear stress; von Willebrand factor