新型第三代二氢吡啶类钙通道拮抗剂阿折地平对人内乳动脉的血管舒张作用。

Vasorelaxation induced by new third-generation dihydropyridine calcium antagonist azelnidipine in human internal mammary artery.

机构信息

TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China.

TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China.

出版信息

Ann Thorac Surg. 2013 Oct;96(4):1316-1321. doi: 10.1016/j.athoracsur.2013.05.020. Epub 2013 Jul 26.

DOI:10.1016/j.athoracsur.2013.05.020

PMID:23895889

Abstract

BACKGROUND

Graft spasm remains challenging in coronary artery bypass graft (CABG) surgery. Calcium antagonists are commonly used in patients with coronary artery disease. We investigated the inhibitory effect of the new third-generation dihydropyridine calcium antagonist azelnidipine on the vasoconstriction in human internal mammary artery (IMA) from patients undergoing CABG.

METHODS

Isolated IMA rings (n = 68, taken from 28 patients) were studied in myograph in two ways: the relaxing effect of azelnidipine on vasoconstrictor-induced precontraction by potassium chloride (KCl) and U46619; and the depressing effect of azelnidipine at plasma concentrations on the contraction.

RESULTS

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 versus -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 < 0.01) and U46619 (from 30.6 ± 4.0 mN to 16.5 ± 2.2 mN, p < 0.05).

CONCLUSIONS

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 for treating and preventing graft spasm.

摘要

背景

在冠状动脉旁路移植术（CABG）中，移植物痉挛仍然是一个挑战。钙拮抗剂通常用于治疗冠状动脉疾病患者。我们研究了新型第三代二氢吡啶类钙拮抗剂阿折地平对 CABG 患者体内内乳动脉（IMA）血管收缩的抑制作用。

方法

用两种方法在离体血管环肌动描记器中研究 IMA 环（n=68，取自 28 名患者）：阿折地平对氯化钾（KCl）和 U46619 引起的血管收缩预收缩的舒张作用；以及阿折地平在血浆浓度下对收缩的抑制作用。

结果

阿折地平引起 KCl 收缩（96.5%±0.7%）和 U46619 收缩（96.5%±1.4%）IMA 环完全舒张（n=8），对 KCl 的作用比 U46619 强 28.8 倍（EC50-7.49±0.21 log M 与-6.03±0.11 log M，p<0.01）。用阿折地平的血浆浓度（-6.1 log M）预处理 IMA 可显著抑制随后对 KCl（从 25.8±2.2 mN 降至 16.0±1.5 mN，p<0.01）和 U46619（从 30.6±4.0 mN 降至 16.5±2.2 mN，p<0.05）的收缩。