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 mu mol/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%) precontract ed radial arteries at -4.5 log(10) M. The EC50 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 EC50 3.8-fold higher (P = .03) fur 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. Conclusion: 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.