Inflammatory activation during coronary artery surgery and its dose-dependent modulation by statin/ACE-inhibitor combination

Alberto Radaelli, Claudia Loardi, Maria Cazzaniga, Giulia Balestri, Caterina DeCarlini, M. Grazia Cerrito, Elena Negro Cusa, Luca Guerra, Stefano Garducci, Danilo Santo, Lorenzo Menicanti, Giovanni Paolini, Arianna Azzellino, Maria Luisa Lavitrano, Giuseppe Mancia, Alberto U. Ferrari

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2750-2755
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume27
Issue number12
DOIs
Publication statusPublished - Dec 2007

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Angiotensin-Converting Enzyme Inhibitors
Coronary Artery Bypass
Coronary Vessels
Transplants
Sexually Transmitted Diseases
Ramipril
E-Selectin
Simvastatin
von Willebrand Factor
Interleukin-6
Cardiovascular Agents
Enalapril
Coronary Sinus
Veins
Anti-Inflammatory Agents
Therapeutics
Ischemia
Arteries
Tumor Necrosis Factor-alpha

Keywords

  • ACE-inhibitors
  • Coronary artery surgery
  • Inflammation
  • Statins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Inflammatory activation during coronary artery surgery and its dose-dependent modulation by statin/ACE-inhibitor combination. / Radaelli, Alberto; Loardi, Claudia; Cazzaniga, Maria; Balestri, Giulia; DeCarlini, Caterina; Cerrito, M. Grazia; Cusa, Elena Negro; Guerra, Luca; Garducci, Stefano; Santo, Danilo; Menicanti, Lorenzo; Paolini, Giovanni; Azzellino, Arianna; Lavitrano, Maria Luisa; Mancia, Giuseppe; Ferrari, Alberto U.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 27, No. 12, 12.2007, p. 2750-2755.

Research output: Contribution to journalArticle

Radaelli, A, Loardi, C, Cazzaniga, M, Balestri, G, DeCarlini, C, Cerrito, MG, Cusa, EN, Guerra, L, Garducci, S, Santo, D, Menicanti, L, Paolini, G, Azzellino, A, Lavitrano, ML, Mancia, G & Ferrari, AU 2007, 'Inflammatory activation during coronary artery surgery and its dose-dependent modulation by statin/ACE-inhibitor combination', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 12, pp. 2750-2755. https://doi.org/10.1161/ATVBAHA.107.149039
Radaelli, Alberto ; Loardi, Claudia ; Cazzaniga, Maria ; Balestri, Giulia ; DeCarlini, Caterina ; Cerrito, M. Grazia ; Cusa, Elena Negro ; Guerra, Luca ; Garducci, Stefano ; Santo, Danilo ; Menicanti, Lorenzo ; Paolini, Giovanni ; Azzellino, Arianna ; Lavitrano, Maria Luisa ; Mancia, Giuseppe ; Ferrari, Alberto U. / Inflammatory activation during coronary artery surgery and its dose-dependent modulation by statin/ACE-inhibitor combination. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2007 ; Vol. 27, No. 12. pp. 2750-2755.
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AU - Radaelli, Alberto

AU - Loardi, Claudia

AU - Cazzaniga, Maria

AU - Balestri, Giulia

AU - DeCarlini, Caterina

AU - Cerrito, M. Grazia

AU - Cusa, Elena Negro

AU - Guerra, Luca

AU - Garducci, Stefano

AU - Santo, Danilo

AU - Menicanti, Lorenzo

AU - Paolini, Giovanni

AU - Azzellino, Arianna

AU - Lavitrano, Maria Luisa

AU - Mancia, Giuseppe

AU - Ferrari, Alberto U.

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N2 - 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.

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