Fasudil is a superior graft vasodilator in coronary artery bypass surgery: internal thoracic artery Running head: Fasudil as potent graft dilator in CABG

Background. Internal thoracic artery (ITA) is a very useful conduit for coronary artery bypass artery (CABG), with excellent long-term patency. With the purpose to dilate the ITA graft and increase graft free flow (GFF) intraoperatively, we evaluated the usefulness of intraluminal injection of fasudil, a Rho-kinase inhibitor, and compared with the conventional graft dilating agent papaverine. Methods. Between June 2011 and January 2012, 30 patients with ischemic heart disease who underwent isolated CABG using ITA were enrolled. The patients were randomly assigned to two groups: fasudil group (n=15) in which fasudil solution 0.9 mg/dl was injected into ITA, and papaverine group (n=15) in which papaverine solution (0.4 mg/ml) mixed with heparinized blood was used. Outcome measures were left ITA GFF, heart rate and mean blood pressure during flow measurements, and histopathological examination of ITA. Results. In the fasudil group, GFF increased significantly (p<0.01) from 19.7±15.2 ml/min at baseline to 66.9±31.7ml/min after fasudil injection. In the papaverine group, GFF increased significantly (p<0.01) from 22.9±17.3 ml/min at baseline to 44.8±26.7 ml/min after papaverine injection. Blood pressure and heart rate did not change significantly after drug injection in both groups. The GFF was significantly higher (p=0.038) in fasudil-treated ITA than in papaverine-treated ITA. Histopathologically, the diameter of the ITA was markedly increased after fasudil injection. Elastica van Gieson staining showed that the multiple elastic lamellae structure was intact. Conclusion. Fasudil exhibited very potent vasodilatatory effect on ITA compared to conventional papaverine resulting in increased GFF. This agent is a useful graft dilating agent.