Direct vasodilator effect of milrinone, an inotropic drug, on arterial coronary bypass grafts

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 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.

Reactivity of the human internal thoracic artery to vasodilators in coronary artery bypass grafting

“…The Phosphodiesterase III inhibitor (PDE III-I) is currently considered to be very effective to prevent vasospasm. The systemic administration of PDE III-I has been reported to increase graft blood flow [9,[23][24][25]. A study on the direct injection into a graft is rare.…”

Efficacy of pre-emptive milrinone in off-pump coronary artery bypass surgery: comparison between patients with a low and normal pre-graft cardiac index

“…However, significant decrease in CO may occur despite relatively well-preserved mean SAP and it is conceivable that the cumulative effect of these transient episodes of reduced CO and reduced perfusion pressure due to elevated RAP in the course of distal anastomoses during OPCAB resulted in a degree of ischemic organ injury at least comparable to CPB [18]. Since milrinone has been reported to have little effect on myocardial oxygen consumption [10] unlike other inotropic agents [11] and to dilate arterial bypass graft [12,13], maintaining or increasing CI and SVI within acceptable range with milrinone in patients with low pre-graft CI was considered to be useful. However, the effect of milrinone on post-operative course seemed to be subclinical.…”

“…There is no significant increase in myocardial oxygen consumption [10] and its myocardial oxygen consumption is lower compared to that of dobutamine [11]. Milrinone has a direct vasodilating effect on arterial grafts [12] and also increases the blood flow in grafted internal mammary artery after cardiopulmonary bypass [13]. It's positive effect on myocardial contractility and coronary blood flow with minimal increase in heart rate and myocardial oxygen consumption make milrinone an inotropic agent of choice for patients undergoing OPCAB.…”

Vascular Relaxant Effects of Toborinone on the Isolated Canine Internal Mammary Artery

“…Recent reports by Salmenpera and Levy 8 and Liu et al 15 suggested that phosphodiesterase inhibitors may be useful for preventing or treating an IMA spasm, using human IMA rings. Since toborinone possesses a phosphodiesterase inhibitory action, we performed this experiment in an explanted canine IMA model.…”