A New Method for Antispastic Effect in Coronary Artery Bypass Grafts by Using a L- and T-Type Calcium Channel Blocker Efonidipine.

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.