The in vitro effects of phosphodiesterase inhibitors on the human internal mammary artery.
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.
Salmenperä
M
M
Department of Anesthesiology, Helsinki University, Finland.
Levy
J H
JH
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*
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