Inflammatory activation during coronary artery surgery and its dose-dependent modulation by statin/ACE-inhibitor combination.
BACKGROUND
On-pump coronary artery bypass graft (CABG) surgery triggers an inflammatory response (IR) which may impair revascularization. The study aimed at (1) characterizing the temporal profile of the IR by assaying appropriate markers in both systemic and coronary blood, and (2) determining whether (and which doses of) cardiovascular drugs known to have antiinflammatory properties, namely statins and ACE-inhibitors (ACEI), inhibit the response.


RESULTS
Patients scheduled for CABG (n=22) were randomized to statin/ACEI combination treatment at standard doses (STD, ramipril 2.5/simvastatin 20 mg, or atorvastatin 10 mg), or at high doses (HiDo, ramipril 10 mg, or enalapril 20 mg/simvastatin 80 mg, or atorvastatin 40 mg). Plasma levels of interleukin 6, tumor necrosis factor alpha, E-selectin, von Willebrand factor (vWF), and sVCAM-1 were serially assayed (ELISA) before, during, and after CABG. Blood was drawn from an artery, a systemic vein, and the coronary sinus. Myocardial perfusion scans were obtained before and 2 months after surgery in 19 out of 22 subjects. In the STD group both IL-6 and TNF displayed striking increases which were similar at all sites and peaked 10 to 60 minutes after aortic declamping. Such increases were drastically attenuated in the HiDo group. Instead, only modest increases in venous E-selectin, vWF, and sVCAM-1 were observed. Scintigraphic ischemia scores were entirely normalized after versus before CABG in the HiDo but not in the STD treatment group.


CONCLUSIONS
On-pump CABG surgery is associated with an intense systemic inflammatory response, which can be almost completely prevented by early treatment with high (but not standard) doses of ACE-inhibitors and statins.
Radaelli
Alberto
A
Divisione di Riabilitazione Cardiologica - Ospedale San Gerardo, Via Pergolesi, 33, 20052 Monza, Italy.
Loardi
Claudia
C
Cazzaniga
Maria
M
Balestri
Giulia
G
DeCarlini
Caterina
C
Cerrito
M Grazia
MG
Cusa
Elena Negro
EN
Guerra
Luca
L
Garducci
Stefano
S
Santo
Danilo
D
Menicanti
Lorenzo
L
Paolini
Giovanni
G
Azzellino
Arianna
A
Lavitrano
Maria Luisa
ML
Mancia
Giuseppe
G
Ferrari
Alberto U
AU
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000097:blood; D004656:Enalapril / Q000008:administration & dosage; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011758:Pyrroles / Q000008:administration & dosage; D017257:Ramipril / Q000008:administration & dosage; D019821:Simvastatin / Q000008:administration & dosage; D013318:Stroke Volume; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism