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A New Method for Antispastic Effect in Coronary Artery Bypass Grafts by Using a L- and T-Type Calcium Channel Blocker
Xiu-Yun Yin1,2,3, Hai-Tao Hou1,2, Ming-Rui Li1,2
1The Department Cardiovascular Surgery & Institute of Cardiovascular Diseases, TEDA International Cardiovascular Hospital, Tianjin University & Chinese Academy of Medical Sciences, Tianjin, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
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