Effects of preoperative statin therapy on cytokines after cardiac surgery.
BACKGROUND
In addition to their lipid-lowering action, it has been demonstrated that statins can exert direct anti-inflammatory effects. We investigated the effect of preoperative statin therapy on systemic inflammatory markers and myocardial NF-kappaB inhibitor IkappaB-alpha after cardiac surgery.


METHODS
Thirty-six patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass (CPB) with cardioplegia were divided into two groups (statin group, n = 18; control group, n = 18). Plasma concentrations of pro-inflammatory cytokines (tumor necrosis factor alpha [TNFalpha], interleukin [IL]-6, IL-8) and anti-inflammatory IL-10 were measured before and 1, 4, 10, and 24 hours (h) after CPB. Phosphorylated IkappaB-alpha/total IkappaB-alpha ratio was assessed before and after CPB in right atrial biopsies.


RESULTS
Baseline and operative data did not differ between groups. Statin therapy was associated with lower preoperative low-density lipoprotein levels compared to control (73+/-6 vs. 92+/-6 mg/dL; P=0.03). Release of IL-6 was attenuated in the statin group at 4 h (2270+/-599 vs. 5120+/-656 pg/ml; P<0.01) and 10 h (1295+/-445 vs. 3116+/-487 pg/ml; P<0.05) compared to the control group. IL-10 increased after surgery in both groups (P<0.05), but was higher in the statin group at 1 h (66+/-15 vs. 26+/-16 pg/mL; P<0.01). Phosphorylated IkappaB-alpha/total IkappaB-alpha ratio before CPB did not differ between groups, but was elevated after CPB in both groups (P<0.05), indicating enhanced degradation of IkappaB-alpha. Statin therapy had no effect on TNFalpha and IL-8.


CONCLUSIONS
Preoperative statin therapy attenuates the release of pro-inflammatory IL-6 and up-regulates anti-inflammatory IL-10 after cardiac surgery with cardioplegia, but fails to inhibit phosphorylation of myocardial IkappaB-alpha.
Liakopoulos
O J
OJ
Department of Thoracic and Cardiovascular Surgery, University of Göttingen, Göttingen, Germany. oliver@liakopoulos.de
Dörge
H
H
Schmitto
J D
JD
Nagorsnik
U
U
Grabedünkel
J
J
Schoendube
F A
FA
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D005260:Female; D006324:Heart Arrest, Induced / Q000009:adverse effects; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D011183:Postoperative Complications; D017035:Pravastatin / Q000627:therapeutic use; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508609:IL10 protein, human; D015850:Interleukin-6; D011758:Pyrroles; D016753:Interleukin-10; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin