title: Selective venous vasodilator properties of the analgesic metamizole (dipyrone) in a human ex vivo model-implications for postoperative pain management.
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.
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, University of Ulm Medical Center, Albert-Einstein-Allee 23, 89081, Ulm, Germany. markus.hoenicka@uniklinik-ulm.de.
authors.forename: Markus
authors.identifier: http://orcid.org/0000-0002-0986-6340
authors.initials: M
authors.lastname: Hoenicka
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, University of Ulm Medical Center, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Hagen
authors.initials: H
authors.lastname: Gorki
authors.affiliation: Department of Cardioanaesthesia, University of Ulm Medical Center, Ulm, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Traeger
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, University of Ulm Medical Center, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Liebold
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004177:Dipyrone / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects*; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy* / Q000503:physiopathology; D012501:Saphenous Vein / Q000187:drug effects*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology* / Q000633:toxicity; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004177:Dipyrone; D007213:Indomethacin
keywords: Analgesia; Cyclooxygenase; Vasodilation; Venous pooling