title: Influence of low molecular weight heparin preparations on human internal thoracic artery contraction.
abstract: OBJECTIVE
  Low molecular weight heparins (LMWHs) offer practical and potential pharmacological advantages over unfractionated heparin in multiple applications but have not been studied as vasoactive agents. The purpose of this study was to investigate the effects of two commercial preparations of LMWHs, enoxaparin sodium and nadroparin calcium, on vasoconstriction in the human internal thoracic artery (ITA) in vitro.
  
  
  METHODS
  Samples of redundant ITA segments obtained from 36 patients who underwent coronary artery bypass surgery were cut into 3mm wide rings and suspended in 20 ml organ bath. Activity of ITA rings precontracted with 80 mM KCl, 0.1 microM endothelin-1 (ET-1) and 1 microM norepinephrine (NE) after administration of enoxaparin and nadroparin in accumulative concentration ranging from 0.1 to 13.2 UI AXa/ml were recorded under isometric conditions by means of force transducers with digital output. The contraction after 80 mmol KCl, 0.1 microM ET-1 and 1 microM NE administration was treated as a control.
  
  
  RESULTS
  Both studied LMWHs in concentration ranging from 0.12 to 13.2 UI AXa/ml did not change basal tonus and KCl precontracted ITA rings. When used in concentrations higher than 13.2 UI AXa/ml nadroparin but not enoxaparin significantly increased the tension in KCl precontracted arterial rings. In NE and ET-1 precontracted rings enoxaparin and nadroparin caused dose dependent relaxation without significant differences between both preparations. Incubation with nitric oxide blocker-Nomega-NITRO-L-ARGININE (L-NNA) in concentration 0.2 mM caused a significant attenuation of relaxant responses to both studied LMWHs in NE and ET-1 precontracted rings.
  
  
  CONCLUSIONS
  LMWHs can have vasorelaxant effects on the receptor-mediated ITA vasoconstriction. The results suggest that LMWHs-induced relaxation in the human ITA is at least partially caused by nitric oxide release. Although the vasoactive effects are not the primary advantage of these drugs used as antithrombotics, such effects might have some clinical importance in the treatment and prophylaxis of graft spasm.
authors.affiliation: Department of Cardiac Surgery, Medical University Hospital, Bialystok, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Buzun
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kleszczewski
authors.forename: Anna
authors.initials: A
authors.lastname: Kostrzewska
authors.forename: Piotr
authors.initials: P
authors.lastname: Lisowski
authors.forename: Piotr
authors.initials: P
authors.lastname: Oleksza
authors.forename: Ryszard
authors.initials: R
authors.lastname: Jackowski
authors.forename: Anna
authors.initials: A
authors.lastname: Pedzińska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Hirnle
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D017762:Nadroparin / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D009924:Organ Culture Techniques; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D017762:Nadroparin; D019335:Nitroarginine; D009569:Nitric Oxide