title: Changes in myocardial vasoreactivity after drastic reduction of plasma fibrinogen and cholesterol: a clinical study in long-term heart transplant survivors using positron emission tomography.
abstract: BACKGROUND
  Given the central importance of the microvasculature in heart transplant recipients, we investigated the possibility of increasing cardiac perfusion after reduction of low-density lipoprotein (LDL)-cholesterol, lipoprotein (a), C-reactive protein (CRP) and fibrinogen plasma levels after apheresis treatment in transplanted patients.
  
  
  METHODS
  Ten long-term heart transplant recipients were examined with positron emission tomography (PET) to measure myocardial perfusion before and after a single heparin-mediated extracorporeal LDL/fibrinogen precipitation (HELP)-apheresis treatment. PET studies were performed the mornings before and after the apheresis treatment. Myocardial blood flow at rest and during adenosine-induced hyperemia was measured using (13)N-ammonia.
  
  
  RESULTS
  HELP-apheresis reduced the plasma levels of LDL-cholesterol, lipoprotein (a) and C-reactive protein by 48% (p < 0.001), fibrinogen by 42% (p = 0.02), plasma viscosity by 14% (p = 0.004) and erythrocyte aggregation by 28% (p < 0.02). Osmolality (<1%) and hematocrit (<2%) remained stable. A single apheresis treatment increased median corrected rest flow by 17.5% (p = 0.007) and median hyperemic flow by 27% (p = 0.02). Median coronary flow reserve increased by 8.1% (p = 0.09). Hyperemic flow after adenosine infusion increased plasma vascular endothelial growth factor levels only before HELP-apheresis (+60%), indicating better ischemic tolerance after apheresis (p = 0.01).
  
  
  CONCLUSIONS
  Myocardial perfusion in transplanted hearts increases significantly after single HELP-apheresis treatment. The present study is only a proof of concept, providing complementary evidence to clinical long-term studies showing that cholesterol reduction either with statins and/or apheresis improves heart transplant outcome.
authors.affiliation: Institut für Klinische Chemie, Klinikum der Universität München, München, Germany.
authors.forename: Beate R
authors.initials: BR
authors.lastname: Jaeger
authors.forename: Frank M
authors.initials: FM
authors.lastname: Bengel
authors.forename: Kenichi
authors.initials: K
authors.lastname: Odaka
authors.forename: Peter
authors.initials: P
authors.lastname: Uberfuhr
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Labarrere
authors.forename: Stefan
authors.initials: S
authors.lastname: Bengsch
authors.forename: Clemens
authors.initials: C
authors.lastname: Engelschalk
authors.forename: Eckart
authors.initials: E
authors.lastname: Kreuzer
authors.forename: Bruno
authors.initials: B
authors.lastname: Reichart
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Dietrich
authors.initials: D
authors.lastname: Seidel
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D001781:Blood Component Removal; D001809:Blood Viscosity; D011232:Chemical Precipitation; D008078:Cholesterol, LDL / Q000097:blood* / Q000302:isolation & purification; D003326:Coronary Circulation; D005260:Female; D005340:Fibrinogen / Q000032:analysis* / Q000302:isolation & purification; D016027:Heart Transplantation; D006439:Hemodynamics; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D049268:Positron-Emission Tomography; D012039:Regional Blood Flow; D012307:Risk Factors
chemical_list: D000925:Anticoagulants; D008078:Cholesterol, LDL; D005340:Fibrinogen; D006493:Heparin