Liu J J, Doolan L A, Xie B, Chen J R, Buxton B F
Department of Cardiac Surgery, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
J Thorac Cardiovasc Surg. 1997 Jan;113(1):108-13. doi: 10.1016/s0022-5223(97)70405-7.
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 alpha1-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.
米力农是一种具有血管舒张活性的正性肌力药物，已被证明可用于增加心输出量和降低楔压。尽管有这些优点，但尚不清楚这种药物是否可用于治疗冠状动脉搭桥术围手术期的痉挛。本研究旨在探讨米力农对冠状动脉搭桥术患者胸廓内动脉的体外血管作用。结果表明，米力农对去甲肾上腺素诱导的胸廓内动脉收缩产生了强大的、浓度依赖性的预防作用，并且能逆转包括血栓素A2类似物U46619、血管收缩肽内皮素-1和α1-肾上腺素能受体激动剂去氧肾上腺素等受体依赖性药物引起的胸廓内动脉收缩。然而，米力农对用25 mmol/L氯化钾收缩的胸廓内动脉的舒张作用较弱。将米力农与其他血管舒张剂（包括罂粟碱、硝普钠和硝酸甘油）进行比较，结果显示米力农比罂粟碱更有效，但比硝普钠和硝酸甘油效力低。米力农对胸廓内动脉收缩的抑制作用表现为收缩力降低，而不是引起50%最大收缩的激动剂浓度值增加，这表明米力农直接作用于平滑肌发挥其血管舒张作用，而不是作用于膜受体。结果还显示，有内皮和无内皮的胸廓内动脉环之间的舒张作用无显著差异。总之，本研究提供了实验证据，证明米力农是一种强大的、不依赖内皮的人胸廓内动脉直接血管舒张剂，并为未来使用该药物对心脏手术患者围手术期胸廓内动脉痉挛进行临床试验提供了科学依据。
