Advancing coronary artery bypass grafting: the fasudil-nitroglycerin cocktail as a potential antispastic solution

Coronary artery disease accounts for >7 million deaths per year worldwide with >800,000 coronary artery bypass grafting (CABG) procedures performed annually (1).The three main conduits used for myocardial revascularization are the internal thoracic artery (ITA), radial artery (RA), and saphenous vein (SV) (2).Vasospasm occurs during harvesting in a high proportion of grafts that may have both immediate and long term adverse effects (3,4).A variety of antispastic drugs studied have either dilator or anti-constrictor actions.The elegant study by Ding et al. describes the effects of diltiazem, nitroglycerin, urapidil and nicorandil on the ITA, RA and SV both in vitro and in vivo (5).In vivo, the effects of vasodilators on RA free flow and hemodynamic were measured while, in vitro, organ bath studies were performed on the effect of vasodilators in isolated ring preparations of the ITA, RA and SV.In vitro, maximal relaxations with urapidil, nitroglycerin and nicorandil were significantly greater in all vessels than with diltiazem.All three conduits showed similar relaxation with nitroglycerin or with diltiazem, but the relaxation with urapidil in RA was greater than that in the ITA and SV, and RA and SV showed greater relaxation with nicorandil than ITA.In vivo, urapidil and nitroglycerin significantly increased RA blood flow, where potency was greater than diltiazem.It was concluded that nitroglycerin causes a significantly greater relaxation than nicorandil, urapidil and diltiazem in all three graft vessels tested; nitroglycerin, nicorandil and urapidil were more effective in preventing RA spasm than diltiazem.An important point made by the authors was that "… isolated vessels may not completely reflect events in vivo", a situation that may question the validity of certain 'bench to bedside", translational, studies.The suggestion that the Rho-kinase inhibitor, fasudil, may be useful in the treatment of coronary artery surgery was made 20 years ago where fasudil prevented spasm and improved myocardial ischemia suggesting that this compound may be useful to treat intractable and otherwise fatal coronary spasm resistant to intensive conventional vasodilator therapy after CABG (6,7).A more recent study compared the antispastic effect of the commonly used vasodilator, papaverine, with the Rhokinase inhibitor, fasudil, on free flow following intraluminal injection in the isolated ITA (8).Fasudil exhibited a very potent vasodilatory effect compared with conventional papaverine.The authors conclude that the increased graft free flow suggests that fasudil is a useful graft dilating agent and provide an example of histology showing the increased