Extracorporeal circulation (ECC) is a circuit that provides circulatory assistance to
facilitate surgical access to a bloodless and, in some cases (in the case of
cardioplegia) immobile operating field. This strategy has led to technical and procedural
advances in cardiothoracic surgery that would have been unthinkable without bypass
surgery. ECC leads to systemic inflammatory response syndrome and is associated with
postoperative complications, including myocardial dysfunction, respiratory failure, acute
renal failure, neurological dysfunction, coagulation disorders and, finally,
multivisceral failure. Numerous data suggest that inflammation and oxidative stress occur
shortly after the start of bypass surgery and progress over time. ECC-induced SIRS,
similar to sepsis, leads to stimulation and activation of endothelial cells. Circulating
pro-inflammatory cytokines can also directly stimulate endothelial cells, resulting in a
pathological increase in permeability leading to the development of capillary leak
syndrome, causing tissue oedema and impaired oxygen utilisation leading to multiple organ
dysfunctions. Clinical practice has shown that the majority of infants suffer
haemodynamic failure within 4 to 8 hours of the operation. This failure could be related
to a state of vasodilatation (capillary leakage) and/or a low cardiac output syndrome.
The timing of the onset of this failure correlates with peak cytokine secretion. The risk
factors for severe SIRS in paediatric cardiac surgery are low weight, heart disease with
an intra-cardiac right-left shunt, the duration of aortic clamping and the length of the
bypass operation. This state of vasoplegia is associated with an increase in lactate
production, reflecting an imbalance between organ oxygen demand and supply, an increase
in amine requirements and an increase in invasive ventilation time. In many cases,
vasoplegia is associated with low cardiac output syndrome. This syndrome is the most
common post-operative complication in paediatric cardiac surgery. Twenty-five to sixty
per cent of newborns develop low cardiac output syndrome (LCOS) in the 6 to 18 hours
following surgery, with mortality occurring in 20% of cases. Current means of limiting
post-CEC SIRS remain limited. The understanding of inflammatory processes and the
interaction between humoral factors and the cellular immune response has progressed
rapidly over the last decade. Multiple anti-inflammatory strategies have been applied in
the past, significantly reducing cytokine levels without improving clinical outcome. This
means that the amplitude of inflammatory cytokine secretion does not directly predict
patient outcome. Future studies should aim to address new post-CEC prophylactic targets
to improve myocardial and endothelial function. Cardiac metabolism is an important area
of research because it plays a central role in maintaining cardiac function under stress.
In recent years, there has been considerable interest in O-GlcNAcylation, a
post-translational modification of proteins, as it plays a key role in regulating
cellular metabolism and the ability to adapt to stress and cell survival. O-N-acetyl
glucosaminylation, more simply known as O-GlcNAcylation, is a ubiquitous, rapid and
reversible post-translational modification involving the addition of a monosaccharide:
ß-D-N-acetylglucosamine to the serine and threonine residues of proteins. In
physiological conditions, some of the glucose entering the cell is directed towards the
hexosamine biosynthesis pathway (VBH), which leads to the production of UDP-GlcNAc, used
by O-GlcNAc transferase (OGT) to O-GlcNAcylate proteins. The reverse reaction is
catalysed by O-GlcNAcase (OGA). VBH is at the crossroads of several cellular metabolic
pathways (glucose, acetyl-CoA, glutamine, uridine and ATP) and O-GlcNAcylation is
considered to be a metabolic sensor. The number of O-GlcNAcylated targets (+3000
proteins) bears witness to the involvement of this modification in various cellular
functions. O-GlcNAc levels are finely modulated according to the cell's metabolic
environment, enabling it to adapt to stress. This last point is particularly important as
metabolism changes during development and during CEC, which impacts the hexosamine
biosynthesis pathway and therefore O-GlcNAcylation. O-GlcNAcylation is particularly
difficult to study at cardiac level, but the investigators have shown that there is a
close correlation between blood (whole blood) and cardiac O-GlcNAc levels in rats.
Preliminary data in rats have shown that O-GlcNAcylation levels decrease during bypass
surgery and that there is an interest in increasing O-GlcNAcylation levels during bypass
surgery in order to reduce organ failure, but no human data have been published in this
context.