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J Thorac Cardiovasc Surg 2000;119:1039-1045
© 2000 The American Association for Thoracic Surgery

Cardiopulmonary Support And Physiology

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

From Starr Academic Center for Cardiac Surgery, St Vincent Hospital, Portland, Ore, and the Division of Cardiothoracic Surgery and Cardiovascular Research Laboratory, Grantham Hospital, Department of Surgery, University of Hong Kong, Hong Kong.

Supported by Hong Kong Research Grants Council (Grant HKU7280/97M & HKU7246/99M) and St Vincent Medical Foundation, Providence Health System, Portland, Ore.

Address for reprints: Professor Guo-Wei He, MD, PhD, Chair of Cardiothoracic Surgery, The University of Hong Kong, Grantham Hospital, 125 Wong Chuk Hang Road, Aberdeen, Hong Kong (E-mail: gwhe{at}hkucc.hku.hk ).

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 log₁₀ M. The EC₅₀ was higher against K⁺ (–5.85 ± 0.24 log₁₀ M, P = .02) or U46619 (–5.21 ± 0.61 log₁₀ M, P = .03) than phenylephrine (–6.68 ± 0.11 log₁₀ 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) for phenylephrine and 2.2-fold higher for K⁺ (P = .01). Milrinone reduced the U46619 contraction at low concentration (–8.5 log₁₀ M) but had little effect on the maximal contraction.
Conclusion: Milrinone is a potent vasodilator for the radial artery, with possibly higher potency in -adrenoceptor- and depolarizing agent K⁺–mediated, but less potency in thromboxane A₂–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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