The Effect of Statin Therapy on Stimulation of Endothelium-Derived Nitric Oxide before and after Coronary Artery Bypass Surgery
DOI:
https://doi.org/10.1532/HSF98.20091185Abstract
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.
References
Anderson TJ, Uehata A, Gerhard MD, et al. 1995. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 26:1235-41.nBeghetti M, Silkoff PE, Caramori M, Holtby HM, Slutsky AS, Adatia I. 1998. Decreased exhaled nitric oxide may be a marker of cardiopulmonary bypass-induced injury. Ann Thorac Surg 66:532-4.nChello M, Goffredo C, Patti G, et al. 2005. Effects of atorvastatin on arterial endothelial function in coronary bypass surgery. Eur J Cardiothorac Surg 28:805-10.nCorretti M, Anderson TJ, Benjamin EJ, et al. 2002. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39:257-65.nDejam A, Hunter CJ, Pelletier MM, et al. 2005. Erythrocytes are the major intravascular storage sites of nitrite in human blood. Blood 106:734-9.nDowning SW, Edmunds LH Jr. 1992. Release of vasoactive substances during cardiopulmonary bypass. Ann Thorac Surg 54:1236-43.nFurchgott RF. 1996. The 1996 Albert Lasker Medical Research Awards. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. JAMA 276:1186-8.nIgnarro LJ. 2002. After 130 years, the molecular mechanism of action of nitroglycerin is revealed. Proc Natl Acad Sci U S A 99:7816-7.nKerst LL, Mauro VF. 2004. Coronary event secondary prevention with statins irrespective of LDL-cholesterol. Ann Pharmacother 38:1060-4.nKrishnadasan B, Morgan EN, Boyle ED, Verrier ED. 2000. Mechanisms of myocardial injury after cardiac surgery. J Cardiothorac Vasc Anesth 14(suppl 1):6-10.nLevy JH, Tanaka KA. 2003. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 75:S715-20.nMasumoto A, Hirooka Y, Hironaga K, et al. 2001. Effect of pravastatin on endothelial function in patients with coronary artery disease (cholesterol-independent effect of pravastatin). Am J Cardiol 88:1291-4.nRassaf T, Heiss C, Hendgen-Cotta U, et al. 2006. Plasma nitrite reserve and endothelial function in the human forearm circulation. Free Radic Biol Med 41:295-301.nRassaf T, Kleinbongard P, Preik M, et al. 2002. Plasma nitrosothiols contribute to the systemic vasodilator effects of intravenously applied NO: experimental and clinical study on the fate of NO in human blood. Circ Res 91:470-7.nRosenson RS, Tangney CC. 1998. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 279:1643-50.nSimons LA, Sullivan D, Simons J, Celermajer DS. 1998. Effects of atorvastatin monotherapy and simvastatin plus cholestyramine on arterial endothelial function in patients with severe primary hypercholester-olemia. Atherosclerosis 137:197-203.nTsao PS, Aoki N, Lefer DJ, Johnson G 3rd, Lefer AM. 1990. Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat. Circulation 82:1402-12.nWassmann S, Ribaudo N, Faul A, Laufs U, Böhm M, Nickenig G. 2004. Effect of atorvastatin 80 mg on endothelial cell function (forearm blood flow) in patients with pretreatment serum low-density lipoprotein cholesterol levels <130 mg/dl. Am J Cardiol 93:84-8.n
