Vasorelaxant effect of phosphodiesterase-inhibitor milrinone in the human radial artery used as coronary bypass graft.
OBJECTIVE
The radial artery is a spastic coronary bypass graft. We investigated the effect of the phosphodiesterase III inhibitor milrinone on the human radial artery.


METHODS
Radial artery segments (n = 76) taken from 15 patients were studied in an organ chamber. Concentration-relaxation curves for milrinone were established in the radial artery precontracted with 3 vasoconstrictors (phenylephrine, K(+), and U46619). In radial artery rings incubated with therapeutic plasma concentrations of milrinone (7 and 70 micromol/L) for 10 minutes, concentration-contraction curves for the 3 vasoconstrictors were constructed.


RESULTS
Milrinone caused a submaximal relaxation in phenylephrine- (98.6% +/- 1.4%), K(+)- (89.1 +/- 4.5%), or U46619- (74.2 +/- 8.0%) precontracted radial arteries at -4.5 log(10) M. The EC(50) was higher against K(+) (-5.85 +/- 0.24 log(10) M, P =.02) or U46619 (-5. 21 +/- 0.61 log(10) M, P =.03) than phenylephrine (-6.68 +/- 0.11 log(10) M). Pretreatment with milrinone depressed the contraction by phenylephrine from 70.0% +/- 7.9% to 23.5% +/- 9.3% (P =.003) and by K(+) from 138.6% +/- 5.8% to 73.0% +/- 13.9% (P =.006) and shifted the EC(50) 3.8-fold higher (P =.03) for phenylephrine and 2.2-fold higher for K(+) (P =.01). Milrinone reduced the U46619 contraction at low concentration (-8.5 log(10) M) but had little effect on the maximal contraction.


CONCLUSIONS
Milrinone is a potent vasodilator for the radial artery, with possibly higher potency in alpha-adrenoceptor- and depolarizing agent K(+)-mediated, but less potency in thromboxane A(2)-mediated, contraction. Because it also has a positive inotropic effect, this vasodilator may be particularly indicated for use in patients receiving radial artery grafts in coronary artery bypass grafting.
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Starr Academic Center for Cardiac Surgery, St Vincent Hospital, Portland, Oregon, USA. gwhe@hkucc.hku.hk
Yang
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CQ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D001026:Coronary Artery Bypass; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D020105:Milrinone / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D017534:Radial Artery / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D010726:Phosphodiesterase Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; 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; D011188:Potassium