Copyright © 2002 by the European Society of Cardiology.
Continuous 48-h C1-inhibitor treatment, following reperfusion therapy, in patients with acute myocardial infarction
a Department of Cardiology, University Hospital Maastricht, Maastricht, The Netherlands
b Department of Clinical Chemistry, University Hospital Maastricht, Maastricht, The Netherlands
d Central Laboratory of the Bloodtransfusion Service (CLB), Amsterdam, The Netherlands
c Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands
revised January 29, 2002; accepted February 7, 2002
Abstract
Aims Complement inhibition by C1-inhibitor has been shown to reduce myocardial ischaemia–reperfusion injury in animal models. We therefore studied the effects of intravenous C1-inhibitor, following reperfusion therapy, in patients with acute myocardial infarction.
Methods and Results C1-inhibitor therapy was started not earlier than 6h after acute myocardial infarction, in order to prevent interference with thrombolytic therapy. A loading dose of C1-inhibitor was followed by a continuous infusion for 48h, using three escalating dosage schemes. Efficacy of complement inhibition was estimated from C4 activation fragments. Plasma concentrations of myocardial proteins were compared to values measured in matched control patients. In 22 patients, C1-inhibitor was well tolerated and drug-related adverse events were not observed. Target plasma levels of C1-inhibitor were reached, with values of 48·2ml.kg–1 for distribution space and 35·5h for the half-life time of C1-inhibitor. A dose-dependent reduction of C4 fragments was found P=0·005). In 13 patients who received early thrombolytic therapy, release of troponin T and creatine kinase-MBmass was reduced by 36% and 57%P =0·001), compared to 18 controls.
Conclusion Continuous 48-h treatment with C1-inhibitor provides safe and effective inhibition of complement activation after reperfused acute myocardial infarction and may reduce myocardial injury.
Key Words: Complement inhibition, C1-inhibitor, myocardial infarction.
f1 Correspondence: Wim Th. Hermens, PhD, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Szeplaki, L. Varga, J. Laki, E. Dosa, S. Rugonfalvi-Kiss, H. O. Madsen, Z. Prohaszka, A. Kocsis, P. Gal, A. Szabo, et al. Low C1-Inhibitor Levels Predict Early Restenosis After Eversion Carotid Endarterectomy Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2756 - 2762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Fattouch, G. Bianco, G. Speziale, R. Sampognaro, C. Lavalle, F. Guccione, P. Dioguardi, and G. Ruvolo Beneficial effects of C1 esterase inhibitor in ST-elevation myocardial infarction in patients who underwent surgical reperfusion: a randomised double-blind study Eur. J. Cardiothorac. Surg., August 1, 2007; 32(2): 326 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bao, Y. Wang, A. Chang, A. W. Minto, J. Zhou, H. Kang, M. Haas, and R. J. Quigg Unrestricted C3 Activation Occurs in Crry-Deficient Kidneys and Rapidly Leads to Chronic Renal Failure J. Am. Soc. Nephrol., March 1, 2007; 18(3): 811 - 822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Thielmann, G. Marggraf, M. Neuhauser, J. Forkel, U. Herold, M. Kamler, P. Massoudy, and H. Jakob Administration of C1-esterase inhibitor during emergency coronary artery bypass surgery in acute ST-elevation myocardial infarction. Eur. J. Cardiothorac. Surg., August 1, 2006; 30(2): 285 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Banz, O. M. Hess, S. C. Robson, D. Mettler, P. Meier, A. Haeberli, E. Csizmadia, E. Y. Korchagina, N. V. Bovin, and R. Rieben Locally targeted cytoprotection with dextran sulfate attenuates experimental porcine myocardial ischaemia/reperfusion injury Eur. Heart J., November 1, 2005; 26(21): 2334 - 2343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Theroux, P. W. Armstrong, K. W. Mahaffey, J. S. Hochman, K. J. Malloy, S. Rollins, J. C. Nicolau, J. Lavoie, T. M. Luong, J. Burchenal, et al. Prognostic significance of blood markers of inflammation in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty and effects of pexelizumab, a C5 inhibitor: a substudy of the COMMA trial Eur. Heart J., October 1, 2005; 26(19): 1964 - 1970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Bonvini, T. Hendiri, and E. Camenzind Inflammatory response post-myocardial infarction and reperfusion: a new therapeutic target? Eur. Heart J. Suppl., October 1, 2005; 7(suppl_I): I27 - I36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P A J Krijnen, C Ciurana, T Cramer, T Hazes, C J L M Meijer, C A Visser, H W M Niessen, and C E Hack IgM colocalises with complement and C reactive protein in infarcted human myocardium J. Clin. Pathol., April 1, 2005; 58(4): 382 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. De Simoni, E. Rossi, C. Storini, S. Pizzimenti, C. Echart, and L. Bergamaschini The Powerful Neuroprotective Action of C1-Inhibitor on Brain Ischemia-Reperfusion Injury Does Not Require C1q Am. J. Pathol., May 1, 2004; 164(5): 1857 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kluft and M. P.M. de Maat Genetics of C-Reactive Protein: New Possibilities and Complications Arterioscler. Thromb. Vasc. Biol., November 1, 2003; 23(11): 1956 - 1959. [Full Text] [PDF]
|
|
|
|
 |
|
 H. W.M Niessen, P. A.J Krijnen, C. A Visser, C. J.L.M Meijer, and C Erik Hack Type II secretory phospholipase A2 in cardiovascular disease: a mediator in atherosclerosis and ischemic damage to cardiomyocytes? Cardiovasc Res, October 15, 2003; 60(1): 68 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Granger, K. W. Mahaffey, W. D. Weaver, P. Theroux, J. S. Hochman, T. G. Filloon, S. Rollins, T. G. Todaro, J. C. Nicolau, W. Ruzyllo, et al. Pexelizumab, an Anti-C5 Complement Antibody, as Adjunctive Therapy to Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) Trial Circulation, September 9, 2003; 108(10): 1184 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Mahaffey, C. B. Granger, J. C. Nicolau, W. Ruzyllo, W. D. Weaver, P. Theroux, J. S. Hochman, T. G. Filloon, C. F. Mojcik, T. G. Todaro, et al. Effect of Pexelizumab, an Anti-C5 Complement Antibody, as Adjunctive Therapy to Fibrinolysis in Acute Myocardial Infarction: The COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) Trial Circulation, September 9, 2003; 108(10): 1176 - 1183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nijmeijer, W. K. Lagrand, Y. T. P. Lubbers, C. A. Visser, C. J. L. M. Meijer, H. W. M. Niessen, and C. E. Hack C-Reactive Protein Activates Complement in Infarcted Human Myocardium Am. J. Pathol., July 1, 2003; 163(1): 269 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Poole-Wilson Innovative treatments for myocardial infarction; design, purpose and consequences of early studies Eur. Heart J., November 1, 2002; 23(21): 1640 - 1642. [Full Text] [PDF]
|
|