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Eur J Cardiothorac Surg 2004;26:951-955
© 2004 Elsevier Science NL

Influence of low molecular weight heparin preparations on human internal thoracic artery contraction

Leszek Buzun^a, Tomasz Kleszczewski^b,*, Anna Kostrzewska^b, Piotr Lisowski^a, Piotr Oleksza^a, Ryszard Jackowski^a, Anna Pedziska^b, Tomasz Hirnle^a

^a Department of Cardiac Surgery, Medical University Hospital, Bialystok, Poland
^b Department of Biophysics Medical University of Biaystok, ul Mickiewicza 2A, 15-089 Bialystok, Poland

Received 17 February 2004; received in revised form 6 July 2004; accepted 7 July 2004.

^* Corresponding author. Tel.: +48-85-7485667; fax: +48-85-7468630. (E-mail: kleszczt{at}cksr.ac.bialystok.pl).

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 20ml organ bath. Activity of ITA rings precontracted with 80mM KCl, 0.1µM endothelin-1 (ET-1) and 1µM norepinephrine (NE) after administration of enoxaparin and nadroparin in accumulative concentration ranging from 0.1 to 13.2UI AXa/ml were recorded under isometric conditions by means of force transducers with digital output. The contraction after 80mmol KCl, 0.1µM ET-1 and 1µM NE administration was treated as a control. Results: Both studied LMWHs in concentration ranging from 0.12 to 13.2UI AXa/ml did not change basal tonus and KCl precontracted ITA rings. When used in concentrations higher than 13.2UI 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-N-NITRO-L-ARGININE (L-NNA) in concentration 0.2mM caused a significant attenuation of relaxant responses to both studied LMWHs in NE and ET-1 precontracted rings. Conclusion: 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.