Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study.
OBJECTIVE
In addition to lowering lipid levels, statins might reduce leukocyte-endothelial cell interactions. Therefore, we assessed whether this effect could limit the inflammatory response to cardiopulmonary bypass (CPB) in cardiac surgical patients.


METHODS
Twenty patients undergoing valve or coronary operations with tepid (34 degrees C) CPB were randomized to receive an oral dose of atorvastatin (40 mg the evening before and 40 mg the morning of surgery) or to serve as controls. Pre- and post-CPB blood samples were assayed for neutrophil CD11b surface adhesion molecule and oxidative burst. Plasma levels of interleukins 6 and 8, P-selectin, soluble intercellular adhesion molecule-1, and lactoferrin were measured by enzyme-linked immunosorbent assay (ELISA). In addition, right atrial biopsies were taken before and at the end of CPB, and processed for the expression of the transcription nuclear factor-kappa B (NF-kappaB).


RESULTS
The two groups did not differ with regard to pre- and intraoperative data. Except for P-selectin, postbypass values of all markers significantly increased over baseline values, but atorvastatin therapy failed to attenuate the magnitude of this increase. In the two groups, the expression of NF-kappaB significantly (p = 0.004) increased over baseline without group effect. Postoperative clinical outcomes did not differ either between the two groups.


CONCLUSIONS
These data show that acute preoperative statin therapy fails to limit the inflammatory response to CPB; however, the data also document a major upregulation of NF-kappaB during cardiac operations, thereby providing a sound rationale for interventions targeted at inactivating this key component of the inflammatory cascade.
Florens
E
E
Department of Cardiovascular Surgery, Groupe Hopitalier Bichat-Claude Bernard, and Department of Biochemistry, Hôpital Lariboisière, Paris, France.
Salvi
S
S
Peynet
J
J
Elbim
C
C
Mallat
Z
Z
Bel
A
A
Nguyen
A
A
Tedgui
A
A
Pasquier
C
C
Menasché
P
P
D000368:Aged; D000069059:Atorvastatin; D002315:Cardiopulmonary Bypass; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011300:Preoperative Care; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D011758:Pyrroles; D000069059:Atorvastatin