Abstract
ObjectiveTo investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass.MethodsPatients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli – lipoteichoic acid (LTA) and tumor necrosis factor alpha (TNF) - required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA)-DR, and plasma interleukin (IL)-8, soluble (s)CD62L, soluble (s)Toll-like receptor (TLR)-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation.Results25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively). In contrast, granulocytes (p = 0.01), but not monocytes (p = 0.057) displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p≤0.001) and sTLR (p = 0.004), and decreases in monocyte HLA-DR (p<0.001), plasma sCD62L (p≤0.001). In contrast, ADAM17 plasma levels did not show significant differences over the observation period (p = 0.401).ConclusionsMonitoring granulocyte and monocyte sensitivity using the “CD62L shedding assay” in the perioperative period in cardiac surgical patients treated with the use of cardiopulmonary bypass reveals common changes in sensitivity to TLR2/6 ligands and to TNF stimulus. Further long-term follow-up studies will address the predictive value of these observations for clinical purposes.
Highlights
The clinical introduction of cardiopulmonary bypass (CPB) in 1953 by John Gibbon [1] opened a novel era in cardiac surgery, but confronted clinicians with previously unrecognized issues
This study identified a broad network of molecules involved in CPB-induced immunomodulation, for example, tumor necrosis factor alpha (TNF), interleukin (IL)-1, IL-6, IL-8, and IL10 were found to be increased in CABG patients compared to OPCABG patients postoperatively [8,9,10]
With the use of citrate, which is a weak Ca2+ chelator, we reduced the removal of calcium minimizing interactions with Toll-like receptor (TLR) signaling cascade
Summary
The clinical introduction of cardiopulmonary bypass (CPB) in 1953 by John Gibbon [1] opened a novel era in cardiac surgery, but confronted clinicians with previously unrecognized issues. Clinical correlates range from mild myocardial depression or low systemic vascular resistance to life-threatening complications such as multiorgan failure. Besides this usually transient inflammatory response syndrome some patients acquire nosocomial infections (perioperative incidence 5% and 21% respectively [3,4]) with influence on morbidity and mortality [4,5,6]. Taking into account that the involved markers reach peak plasma levels at different clinical stages, comparisons made on inflammatory markers alone might be misinterpreted [14,15] For this reason it is desirable to assess perioperative immune alterations not exclusively by measuring the concentration of individually selected key mediators at different time points, and at a functional level, by assessing the sensitivity or responsiveness of inflammatory effector cells
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