title: Inhibition of vasoconstriction by phosphodiesterase III inhibitor milrinone in human conduit arteries used as coronary bypass grafts.
abstract: We wished to determine the effect of phosphodiesterase III (PDE III) inhibitor milrinone on human arteries used as coronary bypass grafts. Human internal mammary artery segments (IMA, n = 109) taken from 25 patients were studied. Concentration-relaxation curves for milrinone were established in IMA precontracted with four vasoconstrictors [K+, endothelin-1 (ET-1), U46619, and phenylephrine (PE)]. In IMA rings incubated with therapeutic plasma concentrations of milrinone (7 and 70 microM) for 10 min, concentration-contraction curves for the four vasoconstrictors were constructed. Milrinone caused a complete relaxation in U46619, ET-1, PE (100%), or K+ (97.7%)-precontracted IMA. The EC50 value was higher against K+ (-5.31 +/- 0.27 log M) than PE (-6.20 +/- 0.25 log M, p = 0.036) or endothelin-1 (-6.41 +/- 0.28 log M, p = 0.018). Pretreatment with milrinone decreased the contraction induced by ET-1 from 186.0 +/- 23.3 to 66.9 +/- 9.6% (p = 0.002) and that induced by PE from 140.6 +/- 27.6 to 54.1 +/- 7.0% (p = 0.03) and shifted the EC50 7.6-fold higher (p = 0.003). Treatment of milrinone reduced the K+ and U46619 contraction (p < 0.05) at lower concentrations (between 10 and 80 mM for K+ and -8.5 and -7.5 log M for U46619) and shifted the concentration-contraction curves rightward (2.56-fold higher for K+, p < 0.0001; 3.18-fold higher for U46619, p = 0.007). Denudation of endothelium did not affect the milrinone-induced relaxation. These results demonstrate that milrinone is a potent vasodilator of human conduit arteries used as coronary bypass grafts and may have a slight selectivity with greater potency to receptor stimulants than to the depolarizing agent K+. The results may prove a particular indication for milrinone for use in patients receiving arterial grafts for coronary bypass.
authors.affiliation: Grantham Hospital, Department of Surgery, University of Hong Kong, Hong Kong.
authors.forename: G W
authors.initials: GW
authors.lastname: He
authors.forename: C Q
authors.initials: CQ
authors.lastname: Yang
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D001158:Arteries / Q000187:drug effects* / Q000294:innervation; D002317:Cardiovascular Agents / Q000494:pharmacology; D001026:Coronary Artery Bypass; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D020105:Milrinone; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002317:Cardiovascular Agents; D019332:Endothelin-1; D010726:Phosphodiesterase Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D011728:Pyridones; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D020105:Milrinone