The effect of statin therapy on stimulation of endothelium-derived nitric oxide before and after coronary artery bypass surgery.
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.
Sasmazel
Ahmet
A
Department of Cardiac Surgery, Kartal Kosuyolu Heart and Research Center, Istanbul, Turkey. sasmazel@yahoo.com
Baysal
Ayse
A
Fedekar
Ali
A
Buyukbayrak
Fuat
F
Bugra
Onursal
O
Erdem
Hasan
H
Aydin
Cemalettin
C
Caliskan
Ahmet
A
Sunar
Hasan
H
D000368:Aged; D000069059:Atorvastatin; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy / Q000601:surgery*; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006940:Hyperemia / Q000097:blood; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D005996:Nitroglycerin / Q000008:administration & dosage; D011182:Postoperative Care; D011300:Preoperative Care; D011758:Pyrroles / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000069059:Atorvastatin; D005996:Nitroglycerin