Yin Xiu-Yun, Hou Hai-Tao, Li Ming-Rui, Yang Qin, He Guo-Wei
The Department Cardiovascular Surgery & Institute of Cardiovascular Diseases, TEDA International Cardiovascular Hospital, Tianjin University & Chinese Academy of Medical Sciences, Tianjin, China.
Tianjin Key Laboratory of Molecular Regulation of Cardiovascular Diseases and Translational Medicine, Tianjin, China.
Basic Clin Pharmacol Toxicol. 2025 Aug;137(2):e70077. doi: 10.1111/bcpt.70077.
Internal mammary artery (IMA) is the most commonly used graft in coronary artery bypass grafting (CABG). Spasm of the IMA is a long-recognized problem with the reported prevalence of 0.43% in all CABG surgery. This study explored the antispastic effect and the mechanism of a new generation of dihydropyridine calcium channel blocker efondipine in the IMA.
Discarded distal IMA taken from 54 patients undergoing CABG were collected. The concentration-relaxation curves of efonidipine (-12 to -4.5 log M) in the IMA precontracted with KCl or U46619 were constructed, and the effect was compared to a T-type calcium channel blocker, mibefradil. The pretreatment effect of efonidipine on the contraction of vasoconstrictors was also studied. The Cav1.2 and Cav3.1 protein expression was detected by Western blot.
Efonidipine-induced dose-dependent relaxation in the IMA precontracted with KCl or U46619 (p < 0.05). Pretreatment with -6.5 log M of efonidipine significantly inhibited the vasoconstriction by KCl (p < 0.01) or U46619 (p = 0.04). Cav1.2 and Cav3.1 protein expression levels were significantly decreased by efonidipine. The relaxation effect of efonidipine was significantly greater than that of mibefradil.
The present study revealed a significant antispastic effect of efonidipine in the human IMA due to its effect on the expression of L-type (Cav1.2) and T-type (Cav3.1) proteins. The dual effect of efonidipine on both L- and T-type calcium channels is significantly greater than that of T-type calcium channel blockers. These findings suggest that efonidipine is an effective drug to prevent and treat vasospasm of the IMA during CABG surgery.
乳内动脉（IMA）是冠状动脉旁路移植术（CABG）中最常用的移植物。IMA痉挛是一个早已被认识到的问题，在所有CABG手术中报告的发生率为0.43%。本研究探讨了新一代二氢吡啶类钙通道阻滞剂依福地平对IMA的抗痉挛作用及其机制。
收集54例行CABG患者废弃的IMA远端。构建依福地平（-12至-4.5 log M）在KCl或U46619预收缩的IMA中的浓度-舒张曲线，并将其效果与T型钙通道阻滞剂米贝地尔进行比较。还研究了依福地平对血管收缩剂收缩的预处理作用。通过蛋白质印迹法检测Cav1.2和Cav3.1蛋白表达。
依福地平在KCl或U46619预收缩的IMA中诱导剂量依赖性舒张（p < 0.05）。用-6.5 log M依福地平预处理可显著抑制KCl（p < 0.01）或U46619（p = 0.04）引起的血管收缩。依福地平可显著降低Cav1.2和Cav3.1蛋白表达水平。依福地平的舒张作用明显大于米贝地尔。
本研究表明依福地平对人IMA具有显著的抗痉挛作用，这归因于其对L型（Cav1.2）和T型（Cav3.1）蛋白表达的影响。依福地平对L型和T型钙通道的双重作用明显大于T型钙通道阻滞剂。这些发现表明依福地平是预防和治疗CABG手术期间IMA血管痉挛的有效药物。
