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(Circulation. 2005;112:3272-3279.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

Myocardial Ischemia Induces Interleukin-6 and Tissue Factor Production in Patients With Coronary Artery Disease

A Dobutamine Stress Echocardiography Study

Ignatios Ikonomidis, MD; George Athanassopoulos, MD; John Lekakis, MD; Kyriaki Venetsanou, PhD; Margarita Marinou, BSc; Kimon Stamatelopoulos, MD; Dennis V. Cokkinos, MD; Petros Nihoyannopoulos, MD, FRCP

From the Department of Clinical Therapeutics, University of Athens, Alexandra Hospital, Athens, Greece (I.I., J.L., K.V., K.S.); First Department of Cardiology, Onassis Cardiac Surgery Center, Kallithea, Greece (G.A., M.M., D.V.C.); and Imperial College School of Medicine, National Heart and Lung Institute, Cardiology Department, Hammersmith Hospital, London, UK (P.N.).

Correspondence to Ignatios Ikonomidis, MD, FESC, Second Cardiology Department, University of Athens, Attikon Hospital, Perikleous 19, N Chalkidona, Athens 14343, Greece. E-mail ignoik{at}otenet.gr

Received December 26, 2004; revision received May 22, 2005; accepted August 1, 2005.

Background— Interleukin-6 (IL-6) and macrophage colony stimulating factor plasma levels are elevated in acute coronary syndromes. IL-6 has an inherent negative inotropic action and, with tissue factor (TF), mediates the ischemia-reperfusion myocardial injury. We hypothesized that inducible ischemia leads to cytokine production, TF expression, and consequently persistent left ventricular dysfunction after dobutamine stress echocardiography (DSE) in coronary artery disease patients.

Methods and Results— DSE was performed in 103 patients with angiographically documented coronary artery disease. Blood samples were obtained at rest, at peak stress, and 30 minutes after cessation of dobutamine infusion for measurement of macrophage colony stimulating factor, IL-6, and TF. New or worsening wall motion abnormalities at peak stress and their duration into recovery were noted. Median IL-6 and TF levels were increased at peak stress and at 30 minutes into recovery compared with rest (2.7 and 2.4 versus 2.1 pg/mL for IL-6, 310 and 385 versus 266 pg/mL for TF [P<0.01] in patients with an ischemic response; n=55). Compared with rest, a greater release of IL-6 at peak stress and recovery was observed in patients with increasing number of ischemic segments at peak DSE (2 versus 3 to 4 versus 5 to 6 versus 7 to 8 segments; P=0.03). The time to recovery of wall motion abnormalities was also associated with IL-6 levels at peak stress and recovery (r=0.51 and r=0.39, P<0.05). Macrophage colony stimulating factor levels remained unchanged throughout DSE.

Conclusions— Reversible ischemia induced during DSE increases IL-6 and TF plasma levels. IL-6 is related to the extent of left ventricular dysfunction at peak stress and to persistent LV dysfunction during recovery.

Key Words: echocardiography • hypoxia • interleukins • ischemia • tissue factor

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