Low-Dose Spironolactone: Effects on Artery-to-Artery Vein Grafts and Percutaneous Coronary Intervention Sites

The efficacy of vein grafts used in coronary and peripheral artery bypass is limited by excessive hyperplasia and fibrosis that occur early after engraftment. In the present study, we sought to determine whether low-dose spironolactone alleviates maladaptive vein graft arterialization and alters intimal reaction to coronary artery stenting. Yorkshire pigs were randomized to treatment with oral spironolactone 25 mg daily or placebo. All animals underwent right carotid artery interposition grafting using a segment of external jugular vein and, 5 days later, underwent angiography of carotid and coronary arteries. At that time, a bare metal stent was placed in the left anterior descending artery and balloon angioplasty was performed on the circumflex coronary artery. Repeat carotid and coronary angiograms were performed before euthanasia and graft excision at 30 days. Angiography revealed that venous grafts of spironolactone-treated animals had lumen diameters twice the size of controls at 5 days, a finding that persisted at 30 days. However, neointima and total vessel wall areas also were 2- to 3-fold greater in spironolactone-treated animals, and there were no differences in vessel wall layer thicknesses or collagen and elastin densities. In the coronary circulation, there were no differences between treatment groups in any vessel wall parameters in either stented or unstented vessels. Taken together, these observations suggest that low-dose spironolactone may exert a novel protective effect on remodeling in venous arterial grafts that does not depend on the reduction of hyperplastic changes but may involve dilatation of the vessel wall.