(Circulation. 1995;92:748-755.)
© 1995 American Heart Association, Inc.
Articles |
Cardiac Release of Cytokines and Inflammatory Responses in Acute Myocardial Infarction
Presented in part at the 67th Annual Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994.
From the Medizinische Klinik der Technischen Universität and the Abteilung Klinische Chemie und Klinische Biochemie an der Chirurgischen Innenstadtklinik der Ludwig-Maximilians-Universität (M.J.), München, Germany.
Correspondence to Priv-Doz Dr Franz-Josef Neumann, Medizinische Klinik der Technischen Universität, Ismaninger Str 22, 81675 München, Germany. E-mail neumann@med1.med.tu-muenchen.de.
Background In animal models of myocardial infarction (MI), inflammatory responses compromise microcirculation during reperfusion and restrict functional recovery. To investigate cardiac inflammatory responses in patients with acute MI, we examined the cardiac release of cytokines, the expression on neutrophils of the ß2-integrin Mac-1 (CD11b/CD18) and L-selectin (CD62L), and the cardiac release of thrombomodulin as a marker of endothelial injury.
Methods and Results In 12 patients with acute anterior MI, blood
samples were obtained from the coronary sinus and from the
aorta immediately before and after recanalization
of the coronary occlusion by balloon angioplasty. Twelve
patients undergoing elective balloon angioplasty served as control
subjects. Plasma concentrations of interleukin (IL)-1ß, IL-6, IL-8,
tumor necrosis factor-
, and thrombomodulin were determined by
immunoassay, and surface expression of CD11b and CD62L was assessed by
flow cytometry. Differences in coronary sinus and
arterial blood were found in IL-6 before (median, 6.3 ng/L,
P=.01) and after (13.4 ng/L, P=.002)
recanalization and in IL-8 after
recanalization (10.7 ng/L, P=.02). The
cardiac release of both cytokines significantly
(P
.03) increased with reperfusion. Cytokine
release after reperfusion was associated with significant transcardiac
gradients in surface expression on neutrophils of CD11b (10.1 mean
channel of fluorescence intensity [mean fl], P=.01)
and
CD62L (-8.7 mean fl, P=.007) and with a thrombomodulin
release (4.5 µg/L, P=.004). Transcardiac gradients in
IL-1ß and tumor necrosis factor- were not found. None of the
changes found in MI were detectable in the control group.
Conclusions As evidence of cardiac inflammatory responses in reperfused acute MI, the study demonstrates cardiac neutrophil activation with signs of endothelial injury and a release of the proinflammatory cytokines IL-8 and IL-6. These findings may assist in the design of pharmacological interventions aimed at reducing microvascular reperfusion injury.
Key Words: myocardial infarction • endothelium • leukocytes • reperfusion • cytokines
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 D. Zohlnhofer, K. Brand, K. Schipek, G. Pogatsa-Murray, A. Schomig, and F.-J. Neumann Adhesion of Monocyte Very Late Antigen-4 to Endothelial Vascular Cell Adhesion Molecule-1 Induces Interleukin-1{beta}-Dependent Expression of Interleukin-6 in Endothelial Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2000; 20(2): 353 - 359. [Abstract] [Full Text] [PDF]
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G. Liuzzo, L. M. Biasucci, J. R. Gallimore, G. Caligiuri, A. Buffon, A. G. Rebuzzi, M. B. Pepys, and A. Maseri Enhanced inflammatory response in patients with preinfarction unstable angina J. Am. Coll. Cardiol., November 15, 1999; 34(6): 1696 - 1703. [Abstract] [Full Text] [PDF]
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F.-J. Neumann, D. Zohlnhofer, L. Fakhoury, I. Ott, M. Gawaz, and A. Schomig Effect of glycoprotein IIb/IIIa receptor blockade on platelet-leukocyte interaction and surface expression of the leukocyte integrin Mac-1 in acute myocardial infarction J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1420 - 1426. [Abstract] [Full Text] [PDF]
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W. K. Lagrand, C. A. Visser, W. T. Hermens, H. W. M. Niessen, F. W. A. Verheugt, G.-J. Wolbink, and C. E. Hack C-Reactive Protein as a Cardiovascular Risk Factor : More Than an Epiphenomenon? Circulation, July 6, 1999; 100(1): 96 - 102. [Abstract] [Full Text] [PDF]
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S. Wan, M. B. Izzat, T. W. Lee, I. Y.P. Wan, N. L.S. Tang, and A. P.C. Yim Avoiding cardiopulmonary bypass in multivessel CABG reduces cytokine response and myocardial injury Ann. Thorac. Surg., July 1, 1999; 68(1): 52 - 56. [Abstract] [Full Text] [PDF]
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 M. Shibata, K. Ueshima, M. Harada, M. Nakamura, K. Hiramori, S. Endo, N. Sato, H. Mukaida, T. Suzuki, T. Suzuki, et al. Effect of Magnesium Sulfate Pretreatment and Significance of Matrix Metalloproteinase-1 and Interleukin-6 Levels in Coronary Reperfusion Therapy for Patients with Acute Myocardial Infarction Angiology, July 1, 1999; 50(7): 573 - 582. [Abstract] [PDF]
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M. J. Claeys, J. Bosmans, L. Veenstra, P. Jorens, Herbert De Raedt, and C. J. Vrints Determinants and Prognostic Implications of Persistent ST-Segment Elevation After Primary Angioplasty for Acute Myocardial Infarction : Importance of Microvascular Reperfusion Injury on Clinical Outcome Circulation, April 20, 1999; 99(15): 1972 - 1977. [Abstract] [Full Text] [PDF]
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P. W. H. M. Verheggen, M. P. M. de Maat, V. M. Cats, F. Haverkate, A. H. Zwinderman, C. Kluft, and A. V. G. Bruschke Inflammatory status as a main determinant of outcome in patients with unstable angina, independent of coagulation activation and endothelial cell function Eur. Heart J., April 2, 1999; 20(8): 567 - 574. [Abstract] [PDF]
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P. Massoudy, S. Zahler, A. Barankay, B. F. Becker, J. A. Richter, and H. Meisner Sodium nitroprusside during coronary artery bypass grafting: evidence for an antiinflammatory action Ann. Thorac. Surg., April 1, 1999; 67(4): 1059 - 1064. [Abstract] [Full Text] [PDF]
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A. Liebold, C. Keyl, and D. E. Birnbaum The heart produces but the lungs consume proinflammatory cytokines following cardiopulmonary bypass Eur. J. Cardiothorac. Surg., March 1, 1999; 15(3): 340 - 345. [Abstract] [Full Text] [PDF]
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S. Zahler, P. Massoudy, H. Hartl, C. Hahnel, H. Meisner, and B. F Becker Acute cardiac inflammatory responses to postischemic reperfusion during cardiopulmonary bypass Cardiovasc Res, March 1, 1999; 41(3): 722 - 730. [Abstract] [Full Text] [PDF]
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M. Gwechenberger, L. H. Mendoza, K. A. Youker, N. G. Frangogiannis, C. W. Smith, L. H. Michael, and M. L. Entman Cardiac Myocytes Produce Interleukin-6 in Culture and in Viable Border Zone of Reperfused Infarctions Circulation, February 2, 1999; 99(4): 546 - 551. [Abstract] [Full Text] [PDF]
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S. J. Liu, W. Zhou, and R. H. Kennedy Suppression of beta -adrenergic responsiveness of L-type Ca2+ current by IL-1beta in rat ventricular myocytes Am J Physiol Heart Circ Physiol, January 1, 1999; 276(1): H141 - H148. [Abstract] [Full Text] [PDF]
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F.-J. Neumann, R. Blasini, C. Schmitt, E. Alt, J. Dirschinger, M. Gawaz, A. Kastrati, and A. Schomig Effect of Glycoprotein IIb/IIIa Receptor Blockade on Recovery of Coronary Flow and Left Ventricular Function After the Placement of Coronary-Artery Stents in Acute Myocardial Infarction Circulation, December 15, 1998; 98(24): 2695 - 2701. [Abstract] [Full Text] [PDF]
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N. Marx, F.-J. Neumann, D. Zohlnhofer, T. Dickfeld, A. Fischer, S. Heimerl, and A. Schomig Enhancement of Monocyte Procoagulant Activity by Adhesion on Vascular Smooth Muscle Cells and Intercellular Adhesion Molecule-1–Transfected Chinese Hamster Ovary Cells Circulation, September 1, 1998; 98(9): 906 - 911. [Abstract] [Full Text] [PDF]
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P. Yue, B. M. Massie, P. C. Simpson, and C. S. Long Cytokine expression increases in nonmyocytes from rats with postinfarction heart failure Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H250 - H258. [Abstract] [Full Text] [PDF]
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 D. R. Meldrum Tumor necrosis factor in the heart Am J Physiol Regulatory Integrative Comp Physiol, March 1, 1998; 274(3): R577 - R595. [Abstract] [Full Text] [PDF]
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D. R. Meldrum, J. C. Cleveland Jr, B. S. Cain, X. Meng, and A. H. Harken Increased Myocardial Tumor Necrosis Factor-{alpha} in a Crystalloid-Perfused Model of Cardiac Ischemia-Reperfusion Injury Ann. Thorac. Surg., February 1, 1998; 65(2): 439 - 443. [Abstract] [Full Text] [PDF]
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Y. Miyao, T. Nishikimi, Y. Goto, S. Miyazaki, S. Daikoku, I. Morii, T. Matsumoto, S. Takishita, A. Miyata, H. Matsuo, et al. Increased plasma adrenomedullin levels in patients with acute myocardial infarction in proportion to the clinical severity Heart, January 1, 1998; 79(1): 39 - 44. [Abstract] [Full Text] [PDF]
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K.-i. Kinugawa, T. Shimizu, A. Yao, O. Kohmoto, T. Serizawa, and T. Takahashi Transcriptional Regulation of Inducible Nitric Oxide Synthase in Cultured Neonatal Rat Cardiac Myocytes Circ. Res., December 19, 1997; 81(6): 911 - 921. [Abstract] [Full Text]
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F.-J. Neumann, I. Ott, N. Marx, T. Luther, S. Kenngott, M. Gawaz, M. Kotzsch, and A. Schomig Effect of Human Recombinant Interleukin-6 and Interleukin-8 on Monocyte Procoagulant Activity Arterioscler. Thromb. Vasc. Biol., December 1, 1997; 17(12): 3399 - 3405. [Abstract] [Full Text]
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G. J. Ter Horst and F. Postema Forebrain parasympathetic control of heart activity: retrograde transneuronal viral labeling in rats Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2926 - H2930. [Abstract] [Full Text] [PDF]
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K. Bhagat and P. Vallance Inflammatory Cytokines Impair Endothelium-Dependent Dilatation in Human Veins In Vivo Circulation, November 4, 1997; 96(9): 3042 - 3047. [Abstract] [Full Text]
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C.J.M. Frijns, L.J. Kappelle, J. v. Gijn, H.K. Nieuwenhuis, J.J. Sixma, and R. Fijnheer Soluble Adhesion Molecules Reflect Endothelial Cell Activation in Ischemic Stroke and in Carotid Atherosclerosis Stroke, November 1, 1997; 28(11): 2214 - 2218. [Abstract] [Full Text]
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M. Gawaz, F.-J. Neumann, T. Dickfeld, A. Reininger, H. Adelsberger, A. Gebhardt, and A. Schomig Vitronectin Receptor ({alpha}vß3) Mediates Platelet Adhesion to the Luminal Aspect of Endothelial Cells : Implications for Reperfusion in Acute Myocardial Infarction Circulation, September 16, 1997; 96(6): 1809 - 1818. [Abstract] [Full Text]
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F.-J. Neumann, N. Marx, M. Gawaz, K. Brand, I. Ott, C. Rokitta, C. Sticherling, C. Meinl, A. May, and A. Schomig Induction of Cytokine Expression in Leukocytes by Binding of Thrombin-Stimulated Platelets Circulation, May 20, 1997; 95(10): 2387 - 2394. [Abstract] [Full Text]
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M. Kitakaze, T. Minamino, H. Funaya, K. Node, Y. Shinozaki, H. Mori, and M. Hori Vesnarinone Limits Infarct Size via Adenosine-Dependent Mechanisms in the Canine Heart Circulation, April 15, 1997; 95(8): 2108 - 2114. [Abstract] [Full Text]
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S. Wan, J.-L. LeClerc, and J.-L. Vincent Cytokine Responses to Cardiopulmonary Bypass: Lessons Learned From Cardiac Transplantation Ann. Thorac. Surg., January 1, 1997; 63(1): 269 - 276. [Abstract] [Full Text]
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G. Liuzzo, L. M. Biasucci, A. G. Rebuzzi, J. R. Gallimore, G. Caligiuri, G. A. Lanza, G. Quaranta, C. Monaco, M. B. Pepys, and A. Maseri Plasma Protein Acute-Phase Response in Unstable Angina Is Not Induced by Ischemic Injury Circulation, November 15, 1996; 94(10): 2373 - 2380. [Abstract] [Full Text]
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S. Wan, J.-M. DeSmet, L. Barvais, M. Goldstein, J.-L. Vincent, and J.-L. LeClerc MYOCARDIUM IS A MAJOR SOURCE OF PROINFLAMMATORY CYTOKINES IN PATIENTS UNDERGOING CARDIOPULMONARY BYPASS J. Thorac. Cardiovasc. Surg., September 1, 1996; 112(3): 806 - 811. [Abstract] [Full Text]
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L. M. Biasucci, A. Vitelli, G. Liuzzo, S. Altamura, G. Caligiuri, C. Monaco, A. G. Rebuzzi, G. Ciliberto, and A. Maseri Elevated Levels of Interleukin-6 in Unstable Angina Circulation, September 1, 1996; 94(5): 874 - 877. [Abstract] [Full Text]
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F. M. Sheridan, P. G. Cole, and D. Ramage Leukocyte Adhesion to the Coronary Microvasculature During Ischemia and Reperfusion in an In Vivo Canine Model Circulation, May 15, 1996; 93(10): 1784 - 1787. [Abstract] [Full Text]
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M. Gawaz, F.-J. Neumann, I. Ott, A. Schiessler, and A. Schomig Platelet Function in Acute Myocardial Infarction Treated With Direct Angioplasty Circulation, January 15, 1996; 93(2): 229 - 237. [Abstract] [Full Text]
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