Administration of C1-esterase inhibitor during emergency coronary artery bypass surgery in acute ST-elevation myocardial infarction.
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 < or = 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.
Thielmann
Matthias
M
Department of Thoracic and Cardiovascular Surgery, West-German Heart Center Essen, University Hospital of Essen, 45122 Essen, Germany. matthias.thielmann@uni-essen.de
Marggraf
Günter
G
Neuhäuser
Markus
M
Forkel
Jörg
J
Herold
Ulf
U
Kamler
Markus
M
Massoudy
Parwis
P
Jakob
Heinz
H
D000368:Aged; D003167:Complement Activation / Q000187:drug effects; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D015932:Complement C3c / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D001026:Coronary Artery Bypass; D004334:Drug Administration Schedule; D004630:Emergencies; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000473:pathology / Q000601:surgery*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000517:prevention & control; D019990:Perioperative Care / Q000379:methods; D011446:Prospective Studies; D016896:Treatment Outcome
D003174:Complement C1 Inactivator Proteins; D003181:Complement C4; D015932:Complement C3c