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Eur J Cardiothorac Surg 2006;30:285-293
© 2006 Elsevier Science NL

Administration of C1-esterase inhibitor during emergency coronary artery bypass surgery in acute ST-elevation myocardial infarction

^a Department of Thoracic and Cardiovascular Surgery, West-German Heart Center Essen, University Hospital of Essen, Hufelandstraße 55, 45122 Essen, Germany
^b Institute for Medical Informatics, Biometry, and Epidemiology, University Hospital of Essen, Essen, Germany

Received 4 October 2005; received in revised form 8 April 2006; accepted 20 April 2006.

^_* Corresponding author. Tel.: +49 201 723 4928; fax: +49 201 723 5451. (Email: matthias.thielmann{at}uni-essen.de).

Objective: Myocardial inflammatory response including complement activation was demonstrated as an important mechanism of ischemia–reperfusion injury and complement inhibition by C1-esterase inhibitor (C1-INH) has recently shown to have cardioprotective effects in experimental and clinical settings. Methods: The effects of C1-INH on complement activation, myocardial cell injury, and clinical outcome were studied in patients undergoing emergency CABG due to acute ST-elevation myocardial infarction (STEMI) with (group 1, CABG + STEMI + C1-INH, n = 28) and without (group 2, CABG + STEMI, n = 29) bolus administration of C1-INH (40 IU kg^–1) during reperfusion and 6 h postoperatively (20 IU kg^–1) besides the same study protocol. C1-INH activity, C3c and C4 complement activation fragments, and cardiac troponin I (cTnI) were measured preoperatively and up to 48 h postoperatively and compared to another elective set of CABG patients without STEMI as controls (group 3, CABG–STEMI, n = 10). Clinical data, adverse events, and patient outcome were recorded prospectively. Results: Patient characteristics were not different between groups 1 and 2. No drug-related adverse events were observed. Constant plasma levels of C1-INH were found in group 1, but not in groups 2 and 3. Plasma levels of C3c and C4 complement fragments were reduced in all three groups after surgery throughout the observation time, but tended to be lower in groups 1 and 2 compared with group 3. Preoperative cTnI levels were elevated but not different between the groups 1 and 2. The area under curve (AUC), as well as the postoperative cTnI serum levels, was significantly lower (P < 0.05) in group 1 with a treatment delay 6 h between reperfusion and symptom onset compared to group 2 at 36 h (47.9 ± 11.1 ng/ml vs 97.7 ± 17.2 ng/ml; mean ± SEM), and 48 h (33.5 ± 5.8 ng/ml vs 86.5 ± 19.2 ng/ml) after surgery, but remained unchanged between groups among patients with a treatment delay of more than 6–24 h. In-hospital adverse events and postoperative complications, ICU and hospital stay, as well as in-hospital mortality (14.3% vs 13.8%; P = NS) were not different between groups 1 and 2. Conclusions: C1-INH administration in emergency CABG with acute STEMI is safe and effective to inhibit complement activation and may reduce myocardial ischemia–reperfusion injury as measured by cTnI.

Key Words: Coronary artery bypass grafting • ST-elevation myocardial infarction • Reperfusion injury • C1-esterase inhibitor

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