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J Thorac Cardiovasc Surg 1997;113:108-113
© 1997 Mosby, Inc.

SURGERY FOR ACQUIRED HEART DISEASE

DIRECT VASODILATOR EFFECT OF MILRINONE, AN INOTROPIC DRUG, ON ARTERIAL CORONARY BYPASS GRAFTS

Supported by grants from National Health and Medical Research Council of Australia, Canberra, and Austin Hospital Medical Research Foundation, Heidelberg.

Received for publication August 24, 1995 Revisions requested Nov. 29, 1995 Revisions received April 15, 1996 Accepted for publication July 1, 1996 Address for reprints: James J. Liu, MD, PhD, Vascular Biology Unit, Department of Cardiac Surgery, University of Melbourne, Austin Hospital, Heidelberg, VIC 3084, Australia.

Abstract

Milrinone is an inotropic drug with vasodilator activity that has been shown to be useful in increasing cardiac output and decreasing wedge pressure. Despite these advantages, it is unknown whether this drug can be used for the treatment of perioperative spasm of coronary bypass grafts. This study was undertaken to investigate the in vitro vascular effect of milrinone on internal thoracic arteries obtained from patients undergoing coronary artery bypass grafting. The results showed that milrinone produced a potent, concentration-dependent, preventive effect on the norepinephrine-induced contraction of internal thoracic arteries, as well as reversing contraction of internal thoracic arteries by receptor-dependent agents, including the thromboxane A₂ mimetic U46619, the vasoconstrictor peptide endothelin-1, and the ₁-adrenal receptor agonist phenylephrine. The relaxing effect of milrinone was weaker, however, on internal thoracic arteries contracted with 25 mmol/L potassium chloride. Comparison of milrinone with other vasodilators, including papaverine, nitroprusside, and glyceryl trinitrate, showed milrinone to be more potent than papaverine but less potent than nitroprusside and glyceryl trinitrate. The inhibitory effect of milrinone on internal thoracic artery contraction appeared as a reduction in contractile force, not as an increase in the values of concentrations of the agonists causing 50% maximal contraction, which indicates that milrinone exerts its vasodilator effect directly on the smooth muscles, not on the membrane receptors. The results also showed no significant difference in relaxing effect between internal thoracic artery rings with and without endothelium. In conclusion, this study provides experimental evidence that milrinone is a potent, endothelium-independent, direct vasodilator of the human internal thoracic artery and provides the scientific rationale for a future clinical trial with this drug for the perioperative treatment of internal thoracic artery spasm in cardiac surgical patients. (J Thorac Cardiovasc 1997;113:108-13)

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