Vasorelaxant effect of phosphodiesterase-inhibitor milrinone in the human radial artery used as coronary bypass graft

Abstract

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 μmol/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. Conclusion: Milrinone is a potent vasodilator for the radial artery, with possibly higher potency in α-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. (J Thorac Cardiovasc Surg 2000;119:1039-45)