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 cardioprotective effects in experimental and clinical settings.
The effects of C1-INH on complement activation, perioperative myocardial cellular damage and patients outcome were studied in patients undergoing emergency CABG due to acute ST-elevation myocardial infarction (STEMI) with (group 1,n=25) and without (group 2,n=25) bolus administration of C1-INH (40 IU.kg -1) during reperfusion and 6 hours (hrs) postoperatively (20 IU.kg-1) besides the same study protocol. Complement activation fragments (C4), C1-INH, and cardiac troponin I (cTnI) were measured preoperatively, and at 6, 12, 24, and 48 hrs postoperatively. Clinical data, adverse events and patients outcome were recorded prospectively.
Patient characteristics were not different between groups. No drug-related adverse events could be observed in group 1. Constant plasma levels of C1-INH and a reduction of C4 fragments were found in group 1. Preoperative cTnI levels were elevated but not different between the groups. The postoperative release of cTnI was significantly lower (P<0.05;ANOVA) in group 1 with ≤6hrs between symptom onset and reperfusion compared to group 2 at 12 (38.5±22.1 versus 75.7±24.6 ng/mL), 24 (65.5±24.5 versus 95.2±28.3 ng/mL), and 48hrs (58.3±37.5 versus 87.5±41.2 ng/mL) after surgery, but remained unchanged between the groups among patients with a treatment delay of more than 6hrs. Adverse events, ICU and hospital stay, and in-hospital mortality (13.4% versus 14.3%) were not different between the groups.
The present study is the first to evaluate the effects of complement inhibition during emergency CABG with STEMI. C1-INH effectively inhibited complement activation and did not cause adverse effects. The reduced release of cTnI was only observed in patients, who were treated within the first 6hrs from symptom onset to reperfusion.
C1-INH administration during emergency CABG with acute STEMI is safe and effective to inhibit complement activation and may reduce myocardial ischemia-reperfusion injury in patients undergoing CABG within 6hrs between symptom onset and reperfusion.
Matthias Thielmann, None.