Effect of Amlodipine in Human Internal Mammary Artery and Clinical Implications

Background. Graft spasm remains challenging in CABG (coronary artery bypass grafting) surgery. We investigated the inhibitory effect of a dihydropyridine calcium antagonist amlodipine on the vasoconstriction mediated by potassium chloride (KCl), human urotensin-II (hU-II), and U46619 in human internal mammary artery (IMA) from patients undergoing CABG. Methods. Isolated IMA rings (n = 78, taken from 42 patients) were studied in organ baths in two ways: the relaxing effect of amlodipine on vasoconstrictor-induced precontraction by KCl, hU-II, and U46619 and the depressing effect of amlodipine on the contraction. Results. Amlodipine caused full relaxation in KCl-contracted (98.0% +/- 2.1%), in hU-II-contracted (98.5% +/- 2.4%), and in U46619-contracted (96.3% +/- 1.3%) IMA rings (n = 8) with 15.5-fold higher potency to KCl than to hU-II (effective concentration causing 50% of maximal response [EC50]: -8.17 +/- 0.28 vs -6.98 +/- 0.01 log M, p < 0.001) and 19.5-fold that to U46619 (EC50: -8.17 +/- 0.28 vs -6.88 +/- 0.08 log M, p < 0.001). Pretreatment of IMA with plasma concentrations of amlodipine (-6.6 log M) significantly depressed subsequent contraction to KCl (from 20.8 +/- 2.5 mN to 7.6 +/- 3.0 mN, p = 0.004) and hU-II (from 14.1 +/- 4.2 mN to 3.8 +/- 2.0 mN, p = 0.026), but did not significantly affect the contraction to U46619. Conclusions. We conclude that in human IMA amlodipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Thus, use of amlodipine in CABG patients is favored in treating and preventing graft spasm. (Ann Thorac Surg 2010;90:1952-8) (C) 2010 by The Society of Thoracic Surgeons