Abstract
Metamizole (dipyrone) is a first-line, non-opioid analgesic used for postoperative pain management. Clinical data and animal experiments indicate a possible vasodilator action of this drug. We investigated the effects of metamizole on human artery and vein tone in an ex vivo model to assess potential contributions to venous pooling. Excess segments of bypass grafts were harvested during coronary artery bypass grafting procedures. Tensions were measured in an organ bath for 120 min after adding metamizole to the preconstricted vessels. Contribution of endothelium was assessed in endothelium-denuded vessels, and indometacin was used to identify cyclooxygenase-mediated effects. Internal mammary arteries (n = 6) constricted after addition of 1, 3, and 10 μM metamizole and remained constricted at the lower doses. Transient constrictions also occurred in saphenous veins (n = 20), but veins relaxed below solvent controls after 20 min at all concentrations. Endothelium removal (n = 12) and cyclooxygenase inhibition (n = 12) suppressed the vasoconstrictor effect but not the vasodilator effect. Metamizole and its metabolites display counteracting effects on blood vessel tone ex vivo. The vasoconstrictor effect is mediated by cyclooxygenase-derived products. The net effect is site-specific, resulting in a selective venous vasodilator action. This may exacerbate unwanted venous pooling during postoperative pain therapy.
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The authors are grateful for the expert technical assistance of S. Bergmann and E. Nagel.
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The study was approved by the Ethics Committee of University of Ulm, Germany (300/11) and was conducted in accordance with the Declaration of Helsinki.
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The authors declare that they have no conflicts of interests.
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This article is dedicated to the memory of the late Dietrich E. Birnbaum (February 16, 1942–January 2, 2017), cardiac surgeon, humanitarian worker, and mentor of A.L. and of M.H.
Preliminary data of this project were reported as an oral presentation at the 44th German Society for Thoracic and Cardiovascular Surgery (DGHTG) Annual Meeting in Freiburg, Germany, February 2015.
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Hoenicka, M., Gorki, H., Traeger, K. et al. Selective venous vasodilator properties of the analgesic metamizole (dipyrone) in a human ex vivo model—implications for postoperative pain management. Naunyn-Schmiedeberg's Arch Pharmacol 390, 519–526 (2017). https://doi.org/10.1007/s00210-017-1347-6
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DOI: https://doi.org/10.1007/s00210-017-1347-6