title: The in vitro effects of phosphodiesterase inhibitors on the human internal mammary artery.
abstract: The internal mammary artery (IMA) is the preferred conduit for myocardial revascularization, but it changes diameter in response to injury or thromboxane release to decrease myocardial blood supply. Papaverine, a phosphodiesterase (PDE) inhibitor, is injected in the IMA bed during surgery to prevent spasm. We evaluated the ability of papaverine and cyclic adenosine monophosphate PDE Type III (cAMP-PDE) inhibitors (amrinone, enoximone, and milrinone) in vitro to reverse the constriction of human IMA rings, induced by a thromboxane A2 analog, U46619, and evaluated amrinone's ability to modify the constricting effect of norepinephrine (NE). All cAMP-PDE inhibitors produced complete relaxation of U46619-induced contractions. The contractions necessary to produce 50% relaxation (EC50) were within therapeutic ranges. The vasodilatory potency of amrinone was greater after NE than after U46619 (EC50, 1.9 +/- 0.5 vs 4.3 +/- 2.2 x 10(-5)M; mean +/- SD; P < 0.05). Response to constriction after a submaximal dose of NE was attenuated to 38% (P < 0.001) from that observed in the control rings by a pretreatment with amrinone. These results suggest that cAMP-PDE inhibitors have the potential utility to reverse IMA spasm, and represent a potential therapeutic modality for IMA spasm after myocardial revascularization.
authors.affiliation: Department of Anesthesiology, Helsinki University, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Salmenperä
authors.forename: J H
authors.initials: JH
authors.lastname: Levy
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000676:Amrinone / Q000008:administration & dosage / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D017335:Enoximone / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008323:Mammary Arteries / Q000187:drug effects*; D020105:Milrinone; D009638:Norepinephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010208:Papaverine / Q000008:administration & dosage / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D010726:Phosphodiesterase Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D011728:Pyridones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D017335:Enoximone; D010208:Papaverine; D000242:Cyclic AMP; D020105:Milrinone; D000676:Amrinone; D009638:Norepinephrine