title: Prolonged Mechanical Circumferential Stretch Induces Metabolic Changes in Rat Inferior Vena Cava.
abstract: OBJECTIVE
  Circumferential stretch on the vein wall has been suggested as a potential etiological factor in the development of varicose veins. However, the influence of vein wall stretch on vein metabolism has not yet been explored. The aim of this study was to investigate the effect of short and prolonged mechanical stretch on vein wall metabolism.
  
  
  METHODS
  Circular segments of inferior vena cava from male Sprague-Dawley rats were exposed to normal 0.5-g (nonstretched) or high 2-g (stretched) tension for short (4 h) or prolonged (18 h) duration (five vein segments per group). Contraction response to phenylephrine (10-5M) and KCl (96 mM) was elicited to observe the effect of circumferential stretch on vein function. The polar and organic metabolites in vein tissue were extracted using a bilayer extraction method. Aqueous and organic extracts were analyzed using nuclear magnetic resonance spectroscopy and ultra performance liquid chromatography coupled to mass spectrometry, respectively. Data acquired from both analytical platforms were analyzed using mathematical modeling.
  
  
  RESULTS
  Increased concentrations of valine (p = .02) and choline (p = .03) metabolites and triglyceride moieties (p = .03) were observed in veins stretched for 18 h compared with the nonstretched/18 h group.
  
  
  CONCLUSIONS
  Increased concentrations of branched chain amino acid valine and cell membrane constituent choline indicate increased muscle breakdown and increased metabolism of membrane phospholipids under stretch in an ex-vivo model. Increased intensities of triglyceride moieties in stretched vein segments for 18 h suggest that high pressure may induce an inflammatory response.
  
  
  CONCLUSIONS
  This study has shown that prolonged mechanical circumferential stretch (18 h) alters the metabolic profile of rat inferior vena cava.
authors: Academic Section of Vascular Surgery, Department of Surgery and Cancer, Imperial College, London, UK. Electronic address: m.anwar@imperial.ac.uk.
authors: M A
authors: MA
authors: Anwar
authors: Section of Biomolecular Medicine, Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College, London, UK.
authors: P A
authors: PA
authors: Vorkas
authors: Section of Biomolecular Medicine, Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College, London, UK.
authors: J
authors: J
authors: Li
authors: Section of Biomolecular Medicine, Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College, London, UK.
authors: K N
authors: KN
authors: Adesina-Georgiadis
authors: Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Boston, MA, USA.
authors: O M
authors: OM
authors: Reslan
authors: Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Boston, MA, USA; Vascular Surgery Division, VA Boston Healthcare System, West Roxbury, MA, USA; Harvard Medical School, Boston, MA, USA.
authors: J D
authors: JD
authors: Raffetto
authors: Section of Biomolecular Medicine, Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College, London, UK.
authors: E J
authors: EJ
authors: Want
authors: Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
authors: R A
authors: RA
authors: Khalil
authors: Section of Biomolecular Medicine, Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College, London, UK.
authors: E
authors: E
authors: Holmes
authors: Academic Section of Vascular Surgery, Department of Surgery and Cancer, Imperial College, London, UK.
authors: A H
authors: AH
authors: Davies
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014648:Varicose Veins; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014682:Vena Cava, Inferior / Q000502:physiology*
chemical_list: D014662:Vasoconstrictor Agents; D010656:Phenylephrine
keywords: Circumferential stretch; Metabonomics; Varicose veins; Vascular biology