Complement activation during cardiopulmonary bypass and association with clinical outcomes

Abstract

In this prospective, single‐centre observational study of 30 patients undergoing cardiopulmonary bypass (CPB), the effect of unfractionated heparin (UFH), CPB surgery and protamine sulphate on complement and on post‐operative blood loss were assessed. Although C3 and C4 levels decreased significantly immediately following the administration of UFH, C3a, C5a, Bb fragment and SC5b‐9 remained unchanged. During CPB, C3 and C4 continued to fall whilst both alternative and classical pathways activation markers, Bb, C3a, C5a and SC5b‐9 increased significantly. Protamine sulphate had no effect on classical pathway components or activation markers but decreased alternative pathway activation marker Bb. Over the 12–24 h post‐surgery, both classical and alternative pathway activation markers returned to baseline, whilst C3 and C4 levels increased significantly but not to baseline values. Total drain volume 24 h after the surgery showed a moderate inverse correlation with post‐protamine C3 (r = −0.46, p = 0.01) and C4 (r = −0.57, p = 0.0009) levels, whilst a moderate positive correlation was observed with post‐protamine C3a (r = 0.46, p = 0.009), C5a (r = 0.37, p = 0.04) and SC5b‐9 (r = 0.56, p = 0.001) levels but not with Bb fragment (r = 0.25, p = 0.17). Thus, inhibition of complement activation may be a therapeutic intervention to reduce post‐operative blood in patients undergoing CPB.

The Production of Complement Inhibitor Proteins in Mammalian Cell Lines—Light at the End of the Tunnel?

“…Significant complement activation occurs when blood is drained from the circulatory system, for example, during hemodialysis (>550,000 patients in the USA), hemofiltration, plasmapheresis, plasma exchange, apheresis, extracorporeal membrane oxygenation (ECMO), cardiopulmonary bypass (CPB), and the use of an extracorporeal ventricular assist device [ 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

“…The activity of the complement system has traditionally been attributed to its presence in the circulatory system, but on the basis of accumulated knowledge [43][44][45], separate intracellular [46][47][48], lung [23] and gut (mucosal) [34], neuronal [49,50], tumor microenvironment [51] and breast milk [35,52,53] complement systems can be defined, characterized by the local production of (sometimes non-canonical) components and unique functions (Figure 2). This explosion of knowledge has led to the identification of new drug targets and inhibitor candidates, boosting research funding and also driving investment by Big Pharma.…”

Immunophenotyping of Monocyte Migration Markers and Therapeutic Effects of Selenium on IL-6 and IL-1β Cytokine Axes of Blood Mononuclear Cells in Preoperative and Postoperative Coronary Artery Disease Patients

“…During surgery, the contact of circulating ex vivo blood with non-physiological surfaces additionally exacerbates the degree of inflammation, which might be highly vulnerable for high-risk group comorbid CAD patients with renal failure and diabetes [ 29 , 30 ]. CAD patients who underwent on-pump bypass surgery exhibited increased systemic levels of (i) circulating neutrophils, (ii) neutrophil elastase [ 31 ], (iii) complement components (C3a and C5a) [ 32 ], (iv) platelet activating factors [ 33 ], (v) C-reactive protein (CRP) (an acute phase reactant), (vi) pro-inflammatory cytokines, TNF-α, IL-6, IL-8 [ 34 ], (vii) adhesion molecules (E-selectin, P-selectin, ICAM-1) [ 35 ], and cardiac troponin I [ 36 , 37 , 38 ]. These findings demand a better understanding of complex CAD pathogenesis for further interventional aspects during perioperative and/or postoperative cardiac bypass surgery.…”

Padrões hemodinâmicos pulmonares em pacientes pediátricos com defeitos septais cardíacos congênitos: relação com mediadores inflamatórios e a presença não suspeitada de vírus respiratórios

“…Na população pediátrica, há esforços no sentido de caracterizá-la como fator de risco para o desenvolvimento da assim chamada síndrome de resposta inflamatória sistêmica ("SIRS", em língua inglesa), além de elaborar propostas e estratégias terapêuticas (99,100) . Investigações tem tido como foco mecanismos envolvendo, por exemplo, o sistema complemento (101) , a produção de cininas, tromboxane, prostaglandinas e leucotrienos, além de citocinas pró e antiinflamatórias (102) , produtos de liberação plaquetária, geração de trombina e de outras proteases (99,103,104) .…”