Effect of Azelnidipine in Human Internal Mammary Artery and Clinical Implications

Abstract

Graft spasm remains challenging in coronary artery bypass grafting (CABG) surgery. We investigated the inhibitory effect of a dihydropyridine calcium antagonist azelnidipine on the vasoconstriction mediated by potassium chloride (KCl) and U46619 in human internal mammary artery (IMA) from patients undergoing CABG. Isolated IMA rings (n = 68, taken from 28 patients) were studied in organ baths in two ways: the relaxing effect of azelnidipine on vasoconstrictor‐induced precontraction by KCl and U46619 and the depressing effect of azelnidipine on the contraction. Azelnidipine caused full relaxation in KCl‐contracted (96.5% ± 0.7%) and in U46619‐contracted (96.5% ± 1.4%) IMA rings (n = 8) with 28.8‐fold higher potency to KCl than to U46619 (EC50: −7.49 ± 0.21 vs −6.03 ± 0.11 log M, p < 0.01). Pretreatment of IMA with plasma concentrations of azelnidipine (−6.1 log M) significantly depressed subsequent contraction to KCl (from 25.8 ± 2.2 mN to 16.0 ± 1.5 mN, p < 0.05) and U46619 (from 30.6 ± 4.0 mN to 16.5 ± 2.2 mN, p < 0.01). We conclude that in human IMA azelnidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Thus, use of azelnidipine in CABG patients is favored in treating and preventing graft spasm.Supported by NSF 81170148, 2010CB529500, 2009DFB30560, 09ZCZDSF04200, 10JCYBJC26400, 2012‐BH110004, 2011BHKZ001 & 2011BHKY002, and CUHK4789/09, China.