Beneficial effects of C1 esterase inhibitor in ST-elevation myocardial infarction in patients who underwent surgical reperfusion: a randomised double-blind study.
BACKGROUND
The inflammatory cascade has been hypothesized to be an important mechanism of post-ischaemic myocardial reperfusion injury and several studies demonstrated that C1 esterase inhibitor (C1-INH) is effective in post-ischaemia myocardial protection. Therefore, we aimed to investigate prospectively in a randomised double-blind study the cardioprotective effects of C1-INH in ST segment elevation myocardial infarction (STEMI) in patients who underwent emergent reperfusion with coronary artery bypass grafting (CABG).


METHODS
In this study, we enrolled 80 patients affected with STEMI who underwent emergent CABG. Patients were assigned in two groups (C1-INH group: receive 1000 UI of C1-INH; and placebo group: receive a saline solution). The effects of C1-INH on complement inhibition, myocardial cell injury extension and clinical outcome were studied. Haemodynamic data and myocardial function were monitored. C1-INH, C3a, C4a complement activation fragments and cardiac troponin I (cTnI) serum levels were measured before, during and after surgery.


RESULTS
Patient characteristics were not different between the two groups. The overall in-hospital mortality rate was 6.2%. No statistical significant difference was observed between the two groups with regard to early mortality (p=0.36). Statistical significant difference between the two groups was showed for cardiopulmonary bypass support (p=0.04), administration of high dose of inotropes drugs (p=0.001), time of intubation (p=0.03), intensive care unit (ICU) stay (p=0.04) and in-hospital stay (p=0.03). A significant improvement in mean arterial pressure (p=0.03), cardiac index (p=0.02) and stroke volume (p=0.03) was showed in C1-INH group versus placebo group. The serum cTnI levels were significantly low in the C1-INH group versus placebo group after reperfusion, during the observation period. Plasma levels of C3a and C4a complement fragments were reduced significantly in C1-INH group. No drugs-related adverse effects were observed.


CONCLUSIONS
The inhibition of the classic complement pathway by C1-INH appears to be an effective mean of preserving ischaemic myocardium from reperfusion injury as demonstrated by low serum cTnI levels in C1-INH group. Therefore, the use of C1-INH during CABG as a rescue therapy in STEMI patients is probably an effective treatment to inhibit complement activity and to improve cardiac function and haemodynamic performance without impacting early mortality. Large randomised study should be performed to support our results.
Fattouch
Khalil
K
Unit of Cardiac Surgery, University of Palermo, Palermo, Italy. khalilfattouch@hotmail.com
Bianco
Giuseppe
G
Speziale
Giuseppe
G
Sampognaro
Roberta
R
Lavalle
Carlo
C
Guccione
Francesco
F
Dioguardi
Pietro
P
Ruvolo
Giovanni
G
D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis; D015926:Complement C3a / Q000032:analysis; D015934:Complement C4a / Q000032:analysis; D051056:Complement Inactivating Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis; D001026:Coronary Artery Bypass / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D015425:Myocardial Reperfusion / Q000379:methods*; D011446:Prospective Studies; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood
D002316:Cardiotonic Agents; D003174:Complement C1 Inactivator Proteins; D051056:Complement Inactivating Agents; D019210:Troponin I; D015926:Complement C3a; D015934:Complement C4a