Off-pump CABG surgery reduces systemic inflammation compared to on-pump CABG but does not change endothelial responses: A randomized clinical study

Introduction: Coronary artery bypass graft (CABG) surgery can be followed by
organ failure, due to a systemic inflammatory reaction. To reduce this systemic inflammation, CABG can be performed on the beating heart (off-pump CABG), thereby avoiding cardiopulmonary bypass and cross-clamping of the aorta. There is increasing evidence thatthe endothelium plays an important role in the pathophysiology of organ failure post CABG. When the endothelium becomes activated, it starts to express adhesion molecules and secretes pro inflammatory cytokines [1]. The Angiopoietin (Ang)/Tie2 receptor system and the VEGF/VEGF receptor system are involved in endothelial activation in organ failure [2]. Endothelial activation can be studied by measuring systemic levels of soluble adhesion molecules, and angiogenic and vascular leakage related factors in the plasma [3].

Objectives: To study the effects of off-pump versus on-pump CABG surgery on systemic inflammation and endothelial activation. 

Methods: In this prospective, randomized, observational study, 60 patients who were scheduled for elective CABG surgery were randomized to have surgery for on-pump or offpump CABG. One patient was excluded from the study because off-pump CABG was performed, whereas the patient was randomized for on-pump CABG. Blood was collected at four time points: at start of the procedure, at the end, 6, and 24 h postoperatively. Levels of inflammatory cytokines [IL-6, TNF-a, IL-10, and myeloperoxidase (MPO)], soluble adhesion molecules (E-selectin, VCAM-1, and ICAM-1), and angiogenic factors and their receptors (Ang-1, Ang-2, sTie2, VEGF, sFlt-1, and KDR) were measured in the plasma.

Results: There was no difference in pre-operative characteristics between the patient groups. The inflammatory cytokines TNFa, IL-10 and MPO, but not IL-6, were more increased after the procedure in the on-pump group compared with the off-pump CABG group. The soluble endothelial adhesion molecules E-selectin, VCAM-1, and ICAM-1 showed a similar release pattern in the plasma during and after CABG in on-pump and offpump and were not elevated. Ang-2 was only increased 24 h after surgery, and was not different between on-pump and off-pump group. Higher levels of sFlt-1 were found at the end of the procedure in off-pump CABG compared to on-pump CABG. 

Conclusions: Our study showed that avoiding cardiopulmonary bypass and aortic cross-clamping in CABG surgery reduces the systemic inflammatory response. On-pump CABG does not lead to a higher release of soluble endothelial adhesion molecules in the system compared to off-pump CABG. The systemic levels of angiogenic and vascular leakage related molecules of the endothelial Ang/Tie2 and the VEGF/VEGF receptor system were more deranged from start values in on-pump than in off-pump CABG.

Reference(s): 1. Aird WC. Crit Care Med 2003;31(4 Suppl):S221–30. 2. van Meurs M et al. Crit Care 2009;13(2):207. 3. de Pablo R et al. Eur J Intern Med 2013;24(2):132–138.