Complement Activation and its Prognostic role in Post‐cardiac Arrest Patients

Abstract

Cardiac arrest causes generalized ischaemia/hypoxia, and subsequent resuscitation inflicts reperfusion injury, the pathology of which is not fully understood. Moreover, predicting the prognosis of comatose, post-cardiac arrest patients is a complex clinical challenge. We hypothesized that the extent of complement activation might be a reliable predictor of mortality in this population. Forty-six comatose cardiac arrest patients were enrolled into our prospective cohort study, conducted in a tertiary care university clinic. All subjects were cooled to 32-34°C body temperature for 24 h and then allowed to rewarm to normothermia. All patients underwent diagnostic coronary angiography. On admission, at 6 and 24 h, blood samples were taken from the arterial catheter. In these, complement products (C3a, C3, C4d, C4, SC5b9 and Bb) were measured by ELISA in blood samples. Patients were followed up for 30 days; 22 patients (47.8%) died by the end of this period. We observed that complement activation (determined as the C3a to C3 ratio) was higher in non-survivors than in survivors at each time point. In the multivariate Cox regression analysis, the C3a/C3 ratio determined 24 h after the initiation of therapeutic hypothermia predicted 30-day mortality regardless of age, sex and the APACHE II score. Complement activation occurs in post-cardiac arrest patients, and its extent correlates with 30-day survival. The C3a/C3 ratio might prove useful for estimating the prognosis of comatose postcardiac arrest patients.

The complement lectin pathway after cardiac arrest

“…Targeted temperature management is suggested to reduce complement activation . We found higher levels of MASP‐2 and MASP‐3 and lower levels of M‐ficolin in the prolonged group compared with the standard group.…”

“…Bisschops et al observed that rewarming after cardiac arrest was followed by increasing levels of inflammation products, including C3a and MAC. Furthermore, Jenei et al found that a higher C3a/C3 ratio, a measure of complement activity, was associated with poor survival. In the present study, we found that rewarming was followed by significant increases in MASP‐3 levels (Figure ).…”

“…The complement system is important in the generation of inflammation, and it is involved in ischemia‐reperfusion injuries . This system is activated during cardiac arrest and after resuscitation, and is suggested to be associated with increased mortality after cardiac arrest . The complement system can be activated through the classical, the alternative, and the lectin pathway ( LP ) .…”

Antibodies reactive to cleaved sites in complement proteins enable highly specific measurement of soluble markers of complement activation

“…The most widely used assay for assessment of soluble C4d is manufactured by Quidel and has been used in a number of clinical studies regarding vasculitis (Gou et al, 2013), cardiac arrest (Bisschops et al, 2012) (Jenei et al, 2014), graft rejection (Flechner et al, 2010), mixed cryoglobulinemia (Sansonno et al, 2009), Sjögren's syndrome (Sudzius et al, 2014), lupus (Manzi et al, 1996) and lung cancer (Ajona et al, 2013). According to the manufacturer, this ELISA is based on a neoepitope C4d catching antibody and detection is completed by goat polyclonal anti-C4d.…”

A terápiás hypothermia szerepe a postresuscitatiós ellátásban – irodalmi áttekintés és saját tapasztalatok

“…Ismert, hogy az újraélesztés utáni korai szakban megemelkedik a prokalcitonin szintje, ez azonban az újraélesztés utáni szisztémás reperfúziós válasz súlyossá-gával és nem a korai infekció megjelenésével korrelál [27]. A hypoxiás inzultus következtében megemelkedik a komplementaktivitás is, aminek laborkémiai markerként a jövőben a prognózisbecslésben lehet szerepe [28].…”