The Effect of Simvastatin on Erythrocyte Membrane Fluidity During Oxidative Stress Induced by Cardiopulmonary Bypass: A Randomized Controlled Study

• Published in: Clinical therapeutics Vol. 29; no. 8; pp. 1706 - 1717
• Main Authors: Coccia, Raffaella, PhD, Spadaccio, Cristiano, MD, Foppoli, Cesira, PhD, Perluigi, Marzia, PhD, Covino, Elvio, MD, Lusini, Mario, MD, PhD, Chello, Massimo, MD
• Format: Journal Article
• Language: English
• Published: Belle Mead, NJ EM Inc USA 01.08.2007; Excerpta Medica; Elsevier Limited
• Subjects: Aged; Biological and medical sciences; cardiopulmonary bypass; Cardiopulmonary Bypass - adverse effects; Cell Membrane Permeability - drug effects; Cholesterol; Coronary Artery Bypass; Coronary Artery Disease - blood; Coronary Artery Disease - drug therapy; Coronary Artery Disease - surgery; Diabetes; Double-Blind Method; Erythrocyte Deformability - drug effects; Erythrocyte Membrane - drug effects; Erythrocyte Membrane - metabolism; erythrocytes; Female; Heart surgery; Hemolysis - drug effects; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Internal Medicine; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipids; Male; Medical Education; Medical sciences; Melatonin; Membrane Fluidity - drug effects; Middle Aged; Neutrophils; Oxidative Stress - drug effects; Pharmacology. Drug treatments; Postoperative Complications - prevention & control; Premedication; rheology; Simvastatin - pharmacology; Simvastatin - therapeutic use; Spectrometry, Fluorescence; statin; Statins; Time Factors; Treatment Outcome; Rome Italy; Italy; cardiopulmonary bypass; erythrocytes; rheology; statin; lipid peroxidation; Oxidative stress; Enzyme; Rheology; Simvastatin; Enzyme inhibitor; Red blood cell; Lipids; Statin derivative; Cardiopulmonary bypass; Blood cell; Randomization; Fluidity; Plasma membrane; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Antilipemic agent; Peroxidation
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2007.08.010

Abstract Background: Abnormal erythrocyte deformability can cause severe complications during cardiopulmonary bypass (CPB) surgery, including both hemolysis and perfusion abnormalities. Objectives: The goals of this study were to evaluate changes in erythrocyte membrane fluidity and lipid peroxidation during CPB and to examine the effect of simvastatin treatment on these parameters. Methods: Patients undergoing cardiac surgery involving CPB were selected and randomized to receive either simvastatin 40 mg/d or placebo for 3 weeks before surgery. Three blood samples were obtained at different times during surgery for analysis of erythrocyte membrane fluidity, anion permeability, and lipid peroxidation. Erythrocyte ghosts were prepared and incubated with a lipophilic fluorescent probe (diphenyl-hexatriene), and fluorescence anisotropy was evaluated by spectrophotofluorimetric assay as a measure of membrane fluidity. Anion permeability was evaluated by the specific absorption of methemoglobin (CM ) at 590 and 635 nm after treatment of heparinized blood with NaNO2. The formation of thiobarbituric acid-reactive substances was evaluated as an index of lipid peroxidation. Aspartate transaminase and lactate dehydrogenase were also measured as indices of hemolysis. Results: Forty patients met the inclusion criteria (20 simvastatin, 20 placebo). Their characteristics differed significantly at baseline only in terms of the lipid profile; the statin group had higher levels of high-density lipoprotein cholesterol ( P = 0.01) and lower levels of low-density lipoprotein cholesterol ( P = 0.001) than the placebo group. CPB was found to significantly modify characteristics of the erythrocyte membrane. Compared with preoperative values, CPB induced decreases in both mean (SD) erythrocyte membrane fluidity and anion permeability (preoperative CM : 0.69 [0.02]; 24-hour postoperative CM : 0.18 [0.02]; P < 0.001) and an increase in mean (SD) membrane lipid peroxidation (preoperative malonyl dialdehyde [MDA]: 0.21 [0.01] nmol/mL; postoperative MDA: 0.10 [0.02] nmol/mL; P < 0.001). Treatment with simvastatin was associated with a significant reduction in mean (SD) membrane lipid peroxidation both preoperatively and at 24 hours postoperatively compared with placebo (preoperative MDA: 0.07 [0.01] vs 0.10 [0.02] nmol/mL, respectively; P < 0.05; postoperative MDA: 0.10 [0.04] vs 0.21 [0.01] nmol/mL; P < 0.05). In addition, statin treatment was associated with significant increases in anion permeability preoperatively and postoperatively compared with placebo (preoperative CM : 0.79 [0.01] vs 0.69 [0.02]; P < 0.01; 24-hour postoperative CM : 0.30 [0.01] vs 0.18 [0.02]; P < 0.01). Conclusion: The results of this study suggest that among these patients undergoing CPB surgery, use of simvastatin for 3 weeks before the surgery had significant beneficial effects on erythrocyte membrane fluidity, lipid peroxidation, and anion permeability.