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J Thorac Cardiovasc Surg 1997;114:302-304
© 1997 Mosby, Inc.

LETTERS TO THE EDITOR

Effect of milrinone on coronary artery bypass grafts

Professor of Cardiothoracic Surgery
The University of Hong Kong
Grantham Hospital
125 Wong Chuk Hang Road
Aberdeen, Hong Kong

To the Editor:

The effect of vasodilators on coronary artery bypass grafts is always an interesting topic because the vasoconstriction of the grafts may cause hypoperfusion syndrome, which may cause a serious problem in those who undergo coronary artery bypass with arterial grafts. ¹

With interest, I have read the article authored by Liu and associates ² regarding the effect of a relatively new vasodilator, the phosphodiesterase III inhibitor milrinone, which also possesses inotropic effects. In their study, the authors investigated the effect of milrinone in the human internal thoracic artery with regard to the vasorelaxant effect and the role of endothelium in such effect. Their findings in this article are similar to our previous reports in pharmacology journals. ^3,4 In our reports, we have found that milrinone has vasorelaxant effects against all four vasoconstrictors we tested: potassium, U46619, phenylephrine, and endothelin-1. We have also tested the depressant effect of milrinone on the contraction induced by these vasoconstrictors. ³ In addition, we have found that the vasorelaxant effect of milrinone is endothelium independent. ³ I am glad to see that these results have been reconfirmed by Liu and his associates. Furthermore, we have discovered that milrinone and nitroglycerin have a synergistic effect that is clinically very important, because these two drugs are sometimes used together in the intensive care unit.

However, on the basis of our findings with regard to the effect and the use of milrinone, we would emphasize three points: (1) Relaxation of milrinone in the potassium-precontracted internal thoracic artery is complete at the highest concentration (-4 log M), although the sensitivity to this agent is lower (less potent) than to the other three agents. This demonstrates the selectivity of the vasorelaxant effect of this vasodilator. (2) The inhibitory effect of milrinone in the contraction induced by the four important vasoconstrictors is also slightly selective. It was more potent in inhibition of the receptor-mediated (by endothelin-1 and phenylephrine) than the depolarizing agent potassium-mediated contraction (Fig. 1). This is shown by the more significant suppression effect in the contraction induced by endothelin-1 and phenylephrine. ³ (3) There is a synergistic vasorelaxant effect of the phosphodiesterase III inhibitor milrinone and the nitrovasodilator nitroglycerin in human conduit arteries. This effect may be beneficial to patients undergoing coronary artery bypass grafting and to other patients requiring these vasodilators. Reduced doses of the vasodilators may be sufficient to produce vasodilatation similar to that produced by either of them alone at higher concentrations (Fig. 2) ⁴.

View larger version (17K): [in this window] [in a new window]   Fig. 1. Mean concentration (–log M)-contraction (percentage of 100 mmol/L K+–induced contraction) curves for endothelin-1. Three rings obtained from each patient were allocated to each treatment. One ring was the control () without pretreatment of milrinone. For the other two rings, milrinone 7 µmol/L () or 70 () µmol/L was added into the organ bath 10 minutes before the start of the endothelin-1 curve. Symbols represent data averaged from six rings (from six patients). Vertical error bars are 1 standard error of mean values. **p < 0.01, analysis of variance among the three groups and Scheffe's F test compared with the control at the maximal contraction. Mil, Milrinone. (From He and Yang. Inhibition of Vasoconstriction by Phosphodiesterase III Inhibitor Milrinone in Human Conduit Arteries Used as Coronary Bypass Grafts. J Cardiovasc Pharmacol 1996;28:208-14; published with permission of Lippincott-Raven Publishers, Philadelphia, Pa.)

View larger version (22K): [in this window] [in a new window]   Fig .2 Relaxation induced by milrinone 3 µmol/L (, n = 5), nitroglycerin 10 nmol/L (, n = 5), or a combination of the two (, n = 6) in the human internal thoracic artery precontracted by potassium chloride (K+, 25 mmol/L). , EA+B, Theoretic overadditive curve (see reference 4). *p < 0.05 compared with nitroglycerin and theoretic curve. Vertical error bars are 1 standard error of mean values. Mil, Milrinone; GTN, nitroglycerin. (From He, Yang, Gately, et al. Potential Greater Than Additive Vasorelaxant Actions of Milrinone and Nitroglycerin on Human Conduit Arteries. Br J Clin Pharmacol 1996;41:101-7; published with permission of Blackwell Science Ltd., Oxford, United Kingdom.)

1. The use of milrinone is best indicated when the patient requires vasodilatation as well as inotropic support.
   
2. If an arterial graft is suspected to be in spasm or the patient has symptoms of hypoperfusion syndrome, possibly caused by graft constriction (manifested by low cardiac output, left ventricular failure, rising pulmonary wedge pressure, and hypotension ¹), milrinone may be given as a vasodilator in combination with other therapies in an attempt to dilate the possibly constricted graft or coronary artery. It is particularly indicated when other traditional vasodilators such as nitroglycerin have been used and found to be of little help. In this situation, milrinone is probably well indicated because tolerance to nitroglycerin is suspected.
   
3. When milrinone is used in combination with nitroglycerin, these two vasodilators may have a synergistic vasorelaxant effect. Reduced doses of the vasodilators may be sufficient to obtain the desirable vasorelaxant effect either in bypass grafts or in the systemic (or coronary) circulation.
   

12/8/82352

References

1. Loop FD, Thomas JD. Hypoperfusion after arterial bypass grafting. Ann Thorac Surg 1993;56:812-3.[Medline]
   
2. Liu JJ, Doolan LA, Xie B, Chen JR, Buxton BF. Direct vasodilator effect of milrinone, an inotropic drug, on arterial coronary bypass grafts. J Thorac Cardiovasc Surg 1997;113:108-13.[Abstract/Free Full Text]
   
3. He G-W, Yang C-Q. Inhibition of vasoconstriction by phosphodiesterase III inhibitor milrinone in human conduit arteries used as coronary bypass grafts. J Cardiovasc Pharmacol 1996;28:208-14.[Medline]
   
4. He G-W, Yang C-Q, Gately H, et al. Potential greater than additive vasorelaxant actions of milrinone and nitroglycerin on human conduit arteries. Br J Clin Pharmacol 1996;41:101-7.[Medline]
   

This article has been cited by other articles:

				G.-W. He and C.-Q. Yang Vasorelaxant effect of phosphodiesterase-inhibitor milrinone in the human radial artery used as coronary bypass graft J. Thorac. Cardiovasc. Surg., May 1, 2000; 119(5): 1039 - 1045. [Abstract] [Full Text]

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