title: Macrovascular and microvascular function after implantation of left ventricular assist devices in end-stage heart failure: Role of microparticles.
abstract: BACKGROUND
  The hemodynamic vascular consequences of implanting left ventricular assist devices (LVADs) have not been studied in detail. We investigated the effect of LVAD implantation compared with heart transplant (HTx) on microvascular and macrovascular function in patients with end-stage heart failure and evaluated whether microparticles may play a role in LVAD-related endothelial dysfunction.
  
  
  METHODS
  Vascular function was assessed in patients with end-stage heart failure awaiting HTx, patients who had undergone implantation of a continuous-flow centrifugal LVAD, and patients who had already received a HTx. Macrovascular function was measured by flow-mediated vasodilation (FMD) using high-resolution ultrasound of the brachial artery. Microvascular function was assessed in the forearm during reactive hyperemia using laser Doppler perfusion imaging and pulsed wave Doppler. Age-matched patients without heart failure and without coronary artery disease (CAD) (healthy control subjects) and patients with stable CAD served as control subjects. Circulating red blood cell (CD253(+)), leukocyte (CD45(+)), platelet (CD31(+)/CD41(+)), and endothelial cell (CD31(+)/CD41(-), CD62e(+), CD144(+)) microparticles were determined by flow cytometry and free hemoglobin by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  FMD and microvascular function were significantly impaired in patients with end-stage heart failure compared with healthy control subjects and patients with stable CAD. LVAD implantation led to recovery of microvascular function, but not FMD. In parallel, increased free hemoglobin was observed along with red and white cell microparticles and endothelial and platelet microparticles. This finding indicates destruction of blood cells with release of hemoglobin and activation of endothelial cells. HTx and LVAD implantation led to similar improvements in microvascular function. FMD increased and microparticle levels decreased in patients with HTx, whereas shear stress during reactive hyperemia was similar in patients with LVADs and patients with HTx.
  
  
  CONCLUSIONS
  Our data suggest that LVAD support leads to significant improvements in microvascular perfusion and hemodynamics. However, destruction of blood cells may contribute to residual endothelial dysfunction potentially by increasing nitric oxide scavenging capacity.
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sansone
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine.
authors.forename: Beate
authors.initials: B
authors.lastname: Stanske
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Keymel
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine.
authors.forename: Dominik
authors.initials: D
authors.lastname: Schuler
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine.
authors.forename: Patrick
authors.initials: P
authors.lastname: Horn
authors.affiliation: Department of Cardiovascular Surgery.
authors.forename: Diyar
authors.initials: D
authors.lastname: Saeed
authors.affiliation: Department of Cardiovascular Surgery.
authors.forename: Udo
authors.initials: U
authors.lastname: Boeken
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine.
authors.forename: Ralf
authors.initials: R
authors.lastname: Westenfeld
authors.affiliation: Department of Cardiovascular Surgery; Cardiovascular Research Institute, Heinrich Heine University, Medical Faculty, University of Düsseldorf, Medical Faculty, Düsseldorf, Germany.
authors.forename: Artur
authors.initials: A
authors.lastname: Lichtenberg
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine; Cardiovascular Research Institute, Heinrich Heine University, Medical Faculty, University of Düsseldorf, Medical Faculty, Düsseldorf, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine. Electronic address: christian.heiss@med.uni-duesseldorf.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
mesh_terms: D055252:Cell-Derived Microparticles; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D055806:Microvessels / Q000503:physiopathology*; D008875:Middle Aged; D013997:Time Factors; D014655:Vascular Resistance; D014664:Vasodilation / Q000502:physiology*
keywords: endothelial function; left ventricular assist device; microparticles; microvascular perfusion