Cardiopulmonary Bypass during Cardiac Surgery Modulates Systemic Inflammation by Affecting Different Steps of the Leukocyte Recruitment Cascade

Abstract

BackgroundIt is known that the use of a cardiopulmonary bypass (CPB) during cardiac surgery leads to leukocyte activation and may, among other causes, induce organ dysfunction due to increased leukocyte recruitment into different organs. Leukocyte extravasation occurs in a cascade-like fashion, including capturing, rolling, adhesion, and transmigration. However, the molecular mechanisms of increased leukocyte recruitment caused by CPB are not known. This clinical study was undertaken in order to investigate which steps of the leukocyte recruitment cascade are affected by the systemic inflammation during CPB.MethodsWe investigated the effects of CPB on the different steps of the leukocyte recruitment cascade in whole blood from healthy volunteers (n = 9) and patients undergoing cardiac surgery with the use of cardiopulmonary bypass (n = 7) or in off-pump coronary artery bypass-technique (OPCAB, n = 9) by using flow chamber experiments, transmigration assays, and biochemical analysis.ResultsCPB abrogated selectin-induced slow leukocyte rolling on E-selectin/ICAM-1 and P-selectin/ICAM-1. In contrast, chemokine-induced arrest and transmigration was significantly increased by CPB. Mechanistically, the abolishment of slow leukocyte rolling was due to disturbances in intracellular signaling with reduced phosphorylation of phospholipase C (PLC) γ2, Akt, and p38 MAP kinase. Furthermore, CPB induced an elevated transmigration which was caused by upregulation of Mac-1 on neutrophils.ConclusionThese data suggest that CPB abrogates selectin-mediated slow leukocyte rolling by disturbing intracellular signaling, but that the clinically observed increased leukocyte recruitment caused by CPB is due to increased chemokine-induced arrest and transmigration. A better understanding of the underlying molecular mechanisms causing systemic inflammation after CPB may aid in the development of new therapeutic approaches.

Minimally invasive reoperative aortic valve replacement – A systematic review and meta-analysis

“…Overall, MIrAVR appears to have comparable complication rates and length of stay compared with CrAVR, lending support to its role as a safe alternative to median sternotomy for reoperative AVR. The procedural duration of AVR is of great clinical interest, as prolonged cross-clamp and CPB durations have been shown to be associated with inflammation and poorer surgical outcomes (22,23). In the present study, the cross-clamp and CPB durations were similar between minimally invasive and conventional sternotomy cohorts for rAVR.…”

Comparison of serum cystatin C and creatinine changes after cardiopulmonary bypass in patients with normal preoperative kidney function

“…An alternative explanation, though, is that serum cystatin C levels were raised via increased production through some mechanism induced by cardiac surgery and CPB (e.g. acute inflammation [31]), hence leading to a false-positive diagnosis of AKI. It is thus possible that the faster rise in serum cystatin C compared to serum creatinine during AKI in some studies [23] is due to the fact that the level of the former is also affected by ancillary processes that occur in parallel with the acute decline in GFR, such as inflammation.…”

Inflammatory response and extracorporeal circulation

“…A recently published study demonstrated that cardiac surgery with CPB abrogates selectin-induced slow leucocyte rolling on E-selectin/ICAM-1 and P-selectin/ICAM-1 [46]. By contrast, chemokineinduced arrest and transmigration was significantly increased.…”