Published online before print September 6, 2007, doi: 10.1161/ATVBAHA.107.149039
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© 2007 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Inflammatory Activation During Coronary Artery Surgery and Its Dose-Dependent Modulation by Statin/ACE-Inhibitor Combination
From the Divisione di Riabilitazione Cardiologica (A.R., A.U.F.), Ospedale San Gerardo, Monza; Dipartimento di Medicina Clinica e Prevenzione and Centro Interuniversitario di Fisiologia Clinica e Ipertensione (C.L., M.C., G.B., C.D., G.M., A.U.F.), Dipartimento di Scienze Chirurgiche (M.G.C., G.P., M.L.L.) Università di Milano-Bicocca, Milan, Italy; Divisione di Cardiologia (E.N.C.), Ospedale san Gerardo, Monza, Divisione di Medicina Nucleare (L.G.), Ospedale San Gerardo, Monza; Divisione di Cardiologia (S.G.), Ospedale di Vimercate (Milano), Italy; Cardiochirurgia II (D.S., L.M.), Policlinico San Donato, Università di Milano; Dipartimento di Ingegneria Ambientale (A.A.), Politecnico di Milano, Milan, Italy; and Centro di Bioingegneria, Fondazione Don Gnocchi, Milan, Italy.
Correspondence to Dr Alberto U. Ferrari, Divisione di Riabilitazione Cardiologica – Ospedale San Gerardo, Via Pergolesi, 33, 20052 Monza (MI), Italy. E-mail a.ferrari{at}hsgerardo.org
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.
Methods and 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.
CABG surgery triggers inflammation. Modulation of this response by statins/ACE-inhibitors (ACEI) was tested. Patients undergoing CABG were randomized to statin/ACEI treatment at standard (STD) or high doses (HiDo). Inflammatory mediators were assayed. Striking increases in inflammatory mediators were observed in the STD but not the HiDo group. CABG-related inflammatory response can be prevented by high doses of ACEI/statins.
Key Words: coronary artery surgery • inflammation • statins • ACE-inhibitors