The effect of statin therapy on stimulation of endothelium-derived nitric oxide before and after coronary artery bypass surgery

Abstract

Background: The purpose of this study was to determine the effects of statins on endothelium-derived nitric oxide (NO) levels during coronary artery bypass grafting (CABG) surgery.

Methods: In a prospective study, 130 patients with coronary artery disease were randomized according to preoperative atorvastatin treatment. The patients in group 1 took 40 mg atorvastatin daily for at least 1 month preoperatively, and those in group 2 took no atorvastatin preoperatively. Plasma nitrite and nitrate were measured at baseline and after inducing reactive hyperemia, both before and after surgery. Reactive hyperemia was induced by placing a blood pressure cuff on the upper forearm, inflating it for 5 minutes at 250 mm Hg, and then rapidly deflating the cuff. Blood was collected from the radial artery on the same side 2 minutes after cuff deflation. Plasma levels of total cholesterol, triglycerides, and high- and low-density lipoproteins were measured and analyzed for correlations with NO.

Results: The mean (+/-SD) baseline plasma NO levels before operation were as follows: group 1, 33.97 +/- 18.27 nmol/L; group 2, 24.24 +/- 8.53 nmol/L (P < .001). A significant difference between the 2 groups in plasma NO levels was observed after preoperative reactive hyperemia induction: group 1, 56.43 +/- 15.03 nmol/L; group 2, 43.12 +/- 10.67 nmol/L (P < .001). Two hours after cardiopulmonary bypass (CPB), we observed no significant differences in plasma NO levels, either at baseline (group 1, 11 +/- 3.41 nmol/L; group 2, 9 +/- 5.51 nmol/L) or after reactive hyperemia (group 1, 17.98 +/- 6.77 nmol/L; group 2, 18.00 +/- 6.47 nmol/L). A correlation with preoperative nitroglycerine use was observed (P = .007; r = 0.23). Linear regression analysis (F = 1.463; R = 0.314; R2 = 0.099; P = .16) indicated that the only significant correlation was with preoperative nitroglycerine use (P = .007; t = 2.746).

Conclusions: Preoperative atorvastatin treatment in patients with coronary artery disease increases plasma NO levels before and after reactive hyperemia prior to surgery. CABG surgery with CPB significantly impairs endothelial-derived NO levels, with or without preoperative atorvastatin treatment. Preoperative nitroglycerine use is correlated with higher NO levels after CABG.