Significant Antispastic Effect of Combined Fasudil and Isosorbide Dinitrate on Internal Mammary Artery in Coronary Artery Bypass Grafting.

BACKGROUND: Vasospasm of arterial grafts remains a critical problem in coronary artery bypass grafting (CABG), contributing to perioperative ischemia and graft failure. This study evaluates the antispastic effects of combining the ROCK inhibitor fasudil and isosorbide dinitrate (ISDN) on the human internal mammary artery (IMA).

METHODS: IMA rings (n = 208) from 94 CABG patients were investigated in a myograph. Relaxation to fasudil (-3.5 log M), ISDN (-4 log M) and their combination (FI solution) was assessed after precontraction with potassium chloride (KCl 30 mM) or U46619 (10-8 M). The preventive effects of FI solution on the contraction induced by KCl or U46619 were studied. ROCK2 protein and cGMP levels were measured using Western blot and ELISA.

RESULTS: FI solution demonstrated superior relaxation compared to either drug alone against KCl or U46619 (p < 0.001). Pretreatment with FI inhibited the contraction by KCl and U46619, significantly higher than that with either drug alone (p < 0.0001). FI also reduced ROCK2 expression (p = 0.0001) and elevated cGMP levels (p = 0.0002).

CONCLUSIONS: The combination of fasudil and ISDN effectively prevents and relieves IMA vasospasm mediated by both voltage-operated and receptor-operated calcium channels, with a long-lasting vasorelaxing effect. The FI solution offers a novel approach for preventing and relieving IMA spasm in CABG.