Inflammatory Activation During Coronary Artery Surgery and Its Dose-Dependent Modulation by Statin/ACE-Inhibitor Combination

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 (nϭ22) 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.

Lack of association between body mass index and plasma adiponectin levels in healthy adults

“…IL-6 is estimated to increase from about 1 pg ml À1 at BMI of 22 mg kg À2 to about 2.5 pg ml À1 at BMI of 37 mg kg À2 (a state of severe obesity) (Figure 4b). This increase was very limited in amount compared with the IL-6 level of post-cardiac disease, 91 post-coronary artery bypass surgery patients 92 or experimental low-dose entotoxemia in healthy human subjects. 81 It is not convincing that the slight IL-6 elevation can contribute to the development of obesity-related metabolic diseases.…”

Rosuvastatin Lowers Systemic Inflammatory Response in Coronary Artery Bypass Graft Accompanied by Cardiopulmonary Bypass Surgery: A Randomized Controlled Study

“…It has also been reported that the safe and effective use of statins before and after CABG operations may acting as antiinflammatories that are independent of cholesterol levels [21]. Useful effects can also be obtained by suppressing the inflammatory response by administering higher than standard doses of statins before CABG [22]. In this study, when the results of Group R were evaluated it was concluded that levels of hs-CRP and IL-6,an inflammatory cytokines, could be reduced compared with Group C, and the levels of IL-10, an antiinflammatory cytokine, could be increased at certain times following surgery.…”

Off‐Pump Coronary Artery Bypass Grafting: 30 Years of Debate

“…In RCTs, OPCAB has been associated with significantly lower myocardial injury and increase in inflammatory mediators compared with ONCAB,14, 15 although early mortality rates did not differ significantly 27. Nevertheless, it must be noted that the results of pharmacological treatment aimed at reducing the postoperative inflammatory reaction after CABG (corticosteroids, statins) have been mixed,28, 29 so the role of attempts to modulate inflammation in determining postoperative clinical outcome after CABG remains to be determined.…”