Potent vasodilatory effect of fasudil on radial artery graft in coronary artery bypass operations

Ann Thorac Surg. 2014 Mar;97(3):845-50. doi: 10.1016/j.athoracsur.2013.10.027. Epub 2013 Nov 26.

Abstract

Background: The radial artery (RA) is a useful conduit for coronary artery bypass grafting (CABG) but is susceptible to vasospasm during harvesting. We evaluated the usefulness of fasudil, a Rho kinase inhibitor, in dilating the RA graft and increasing graft free flow (GFF) compared with the conventional graft-dilating agents papaverine and verapamil-nitroglycerin (VG).

Methods: Between June 2012 and January 2013, 45 patients with ischemic heart disease who underwent isolated CABG using the RA were enrolled and randomly assigned to fasudil (n = 15), papaverine (n = 15), or VG (n = 15). Fasudil (2.67 mmol/L), papaverine (1.0 mmol/L) mixed with heparinized blood, or VG (30 μmol/L each of verapamil and nitroglycerin) was injected intraluminally into the RA graft after harvesting. Main outcome measures were RA GFF, hemodynamic changes, and histopathologic examination of the RA.

Results: In the fasudil group, GFF increased significantly (p < 0.001) from 36.8 ± 20.4 at baseline to 148.0 ± 88.3 mL/min after injection. GFF increased significantly (p < 0.001) from 36.0 ± 19.0 to 72.3 ± 36.7 mL/min in the papaverine group and increased significantly (p < 0.001) from 39.5 ± 23.3 to 64.3 ± 29.9 mL/min in the VG group. The GFF was significantly higher (p = 0.001) in fasudil-treated RA than in papaverine- or VG-treated RA. Histopathologically, RA graft diameter was markedly increased after fasudil injection, and the structure of the multiple elastic lamellae was intact. Blood pressure did not change significantly after drug injection in all groups.

Conclusions: Fasudil exhibited a very potent vasodilatory effect on the RA compared with conventional papaverine or VG, resulting in increased GFF. This agent is useful for dilating RA grafts in CABG.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Aged
  • Coronary Artery Bypass*
  • Female
  • Humans
  • Male
  • Nitroglycerin / pharmacology
  • Papaverine / pharmacology
  • Radial Artery / drug effects*
  • Vasodilator Agents / pharmacology*
  • Verapamil / pharmacology

Substances

  • Vasodilator Agents
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Verapamil
  • Papaverine
  • Nitroglycerin
  • fasudil