The effect of simvastatin on erythrocyte membrane fluidity during oxidative stress induced by cardiopulmonary bypass: a randomized controlled study.
BACKGROUND
Abnormal erythrocyte deformability can cause severe complications during cardiopulmonary bypass (CPB) surgery, including both hemolysis and perfusion abnormalities.


OBJECTIVE
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).


CONCLUSIONS
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.
Coccia
Raffaella
R
Department of Biochemical Sciences, University La Sapienza, Rome, Italy.
Spadaccio
Cristiano
C
Foppoli
Cesira
C
Perluigi
Marzia
M
Covino
Elvio
E
Lusini
Mario
M
Chello
Massimo
M
D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D004311:Double-Blind Method; D004907:Erythrocyte Deformability / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011183:Postoperative Complications / Q000517:prevention & control; D011292:Premedication; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin