Ma Qing

Cytokine balance in infants undergoing cardiac operation.

BACKGROUNDnThe control of the systemic inflammatory response taking place during cardiac operations depends on adequate antiinflammatory reaction. In this prospective study we tested the hypothesis that cytokine balance during pediatric cardiac surgical procedures would be influenced by the patients preoperative clinical condition, defined as hypoxemia or heart failure.nnnMETHODSnTwenty infants (median age, 8 months) with hypoxemia owing to intracardiac right-to-left shunt (group 1, n = 10) or with heart failure because of intracardiac left-to-right shunt (group 2, n = 10), scheduled for elective primary corrective operation, were enrolled. Plasma levels of the proinflammatory cytokine interleukin (IL) 6, the natural antiinflammatory cytokine IL-10, and the markers of the acute-phase response, C-reactive protein and procalcitonin, were sequentially measured before, during, and after cardiac operation up to the 10th postoperative day. The ratio of IL-10 to IL-6 levels served as a marker for the individuals antiinflammatory cytokine balance.nnnRESULTSnGroup 1 showed higher preoperative IL-6 (p < 0.001), lower IL-10 levels (p < 0.02), and lower ratio of IL-10 to IL-6 levels (p < 0.001) than group 2. Preoperative C-reactive protein and procalcitonin were not detectable. In group 1, preoperative IL-6 levels inversely correlated with preoperative oxygen saturation (Spearman correlation coefficient, -0.74, p < 0.02). During cardiopulmonary bypass, IL-6 levels were higher, whereas IL-10 and ratio of IL-10 to IL-6 levels were lower in group 1 than in group 2. In all patients, postoperative IL-6 levels were positively correlated with duration of inotropic support and serum creatinine value and inversely correlated with oxygenation index and diuresis.nnnCONCLUSIONSnInfants with hypoxemia show a preoperative inflammatory state with low antiinflammatory cytokine balance in contrast to those with heart failure. This in turn is associated with lower perioperative antiinflammatory cytokine balance and might contribute to postoperative morbidity.

The use of moderate hypothermia during cardiac surgery is associated with repression of tumour necrosis factor-α via inhibition of activating protein-1: an experimental study

IntroductionThe use of moderate hypothermia during experimental cardiac surgery is associated with decreased expression of tumour necrosis factor (TNF)-α in myocardium and with myocardial protection. In order to identify the cellular mechanisms that lead to that repression, we investigated the effect of hypothermia during cardiac surgery on both main signalling pathways involved in systemic inflammation, namely the nuclear factor-κB (NF-κB) and activating protein-1 pathways.MethodTwelve female pigs were randomly subjected to standardized cardiopulmonary bypass with moderate hypothermia or normothermia (temperature 28°C and 37°C, respectively; six pigs in each group). Myocardial probes were sampled from the right ventricle before, during and 6 hours after bypass. We detected mRNA encoding TNF-α by competitive RT-PCR and measured protein levels of TNF-α, inducible nitric oxide synthase and cyclo-oxygenase-2 by Western blotting. Finally, we assessed the activation of NF-κB and activating protein-1, as well as phosphorylation of p38 mitogen-activated protein kinase by electrophoretic mobility shift assay with super shift and/or Western blot.ResultsDuring and after cardiac surgery, animals subjected to hypothermia exhibited lower expression of TNF-α and cyclo-oxygenase-2 but not of inducible nitric oxide synthase. This was associated with lower activation of p38 mitogen-activated protein kinase and of its downstream effector activating protein-1 in hypothermic animals. In contrast, NF-κB activity was no different between groups.ConclusionThese findings indicate that the repression of TNF-α associated with moderate hypothermia during cardiac surgery is associated with inhibition of the mitogen-activated protein kinase p38/activating protein-1 pathway and not with inhibition of NF-κB. The use of moderate hypothermia during cardiac surgery may mitigate the perioperative systemic inflammatory response and its complications.

Systemic inflammatory response to cardiac surgery: does female sex really protect?

Sex hormones have important interactions with the immune system and modulate the inflammatory response. In this regard, oestrogen inhibits the transcription of proinflammatory cytokines and confers tissue protection in experimental models. On the basis of this evidence, Trotter et al. in this issue of Critical Care addressed the question of whether, in children, female sex would protect against the deleterious effects of cardiac operations with cardiopulmonary bypass by providing a favourable anti-inflammatory cytokine balance. The observations made in that study suggest sex-related immunomodulation and organ protection during cardiac surgery in the paediatric population. Prospective trials conducted in large series, including sex hormone determination in neonates, infants and children with congenital cardiac defects, are necessary to test this hypothesis. The verification of sex-related intraoperative organ protection would provide new opportunities for preventing the uncontrolled systemic inflammatory response that may occur during cardiac surgery.

Evaluation of myocardial cell damage in cardiac lymph during cardiopulmonary bypass.

Cardiac lymph is a medium which reflects the myocardial interstitial space. The purpose of our study was to evaluate the inflammatory response marker TNFα (tumor necrosis factor-α) and myocardial injury marker Troponin I during cardiopulmonary bypass (CPB) in cardiac lymph and to compare them with blood values taken from the coronary sinus (SC).