title: Pulsatile ex vivo perfusion of human saphenous vein grafts under controlled pressure conditions increases MMP-2 expression.
abstract: BACKGROUND
  The use of human saphenous vein grafts (HSVGs) as a bypass conduit is a standard procedure in the treatment of coronary artery disease while their early occlusion remains a major problem.
  
  
  METHODS
  We have developed an ex vivo perfusion system, which uses standardized and strictly controlled hemodynamic parameters for the pulsatile and non-static perfusion of HSVGs to guarantee a reliable analysis of molecular parameters under different pressure conditions. Cell viability of HSVGs (n = 12) was determined by the metabolic conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) into a purple formazan dye.
  
  
  RESULTS
  Under physiological flow rates (10 mmHg) HSVGs remained viable for two weeks. Their exposure to arterial conditions (100 mmHg) was possible for one week without important reduction in viability. Baseline expression of matrix metalloproteinase-2 (MMP-2) after venous perfusion (2.2 ± 0.5, n = 5) was strongly up-regulated after exposure to arterial conditions for three days (19.8 ± 4.3) or five days (23.9 ± 6.1, p < 0.05). Zymographic analyses confirmed this increase on the protein level. Our results suggest that expression and activity of MMP-2 are strongly increased after exposure of HSVGs to arterial hemodynamic conditions compared to physiological conditions.
  
  
  CONCLUSIONS
  Therefore, our system might be helpful to more precisely understand the molecular mechanisms leading to an early failure of HSVGs.
authors.affiliation: German Heart Center Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, D-80636 Munich, Germany. dummler@dhm.mhn.de
authors.forename: Sara
authors.initials: S
authors.lastname: Dummler
authors.forename: Stefan
authors.initials: S
authors.lastname: Eichhorn
authors.forename: Christian
authors.initials: C
authors.lastname: Tesche
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schreiber
authors.forename: Bernhard
authors.initials: B
authors.lastname: Voss
authors.forename: Marcus-André
authors.initials: MA
authors.lastname: Deutsch
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.forename: Harald
authors.initials: H
authors.lastname: Lahm
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Lange
authors.forename: Markus
authors.initials: M
authors.lastname: Krane
mesh_terms: D000368:Aged; D001158:Arteries; D003324:Coronary Artery Disease / Q000628:therapy*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D011312:Pressure; D011673:Pulsatile Flow; D012501:Saphenous Vein / Q000378:metabolism / Q000637:transplantation*; D019737:Transplants; D017211:Treatment Failure; D015854:Up-Regulation
chemical_list: C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2