Altered Plasma Metabolites and Deficit in Carnitine System in Patients with Coronary artery Disease Undergoing On-Pump CABG Surgery

Background: Cardiopulmonary bypass (CPB) exposes patients to nonphysiological conditions, leading to significant alterations in organ function and health status of patients with coronary artery disease (CAD). Specifically, CPB activates various pro-inflammatory pathways and imbalances redox homeostasis, causing drastic changes in circulating metabolite profiles. Recent studies have underscored the potential of metabolomics not only to understand pathophysiological processes but also to improve risk stratification and diagnostics. The aim of this study is to characterize the metabolomic changes of patients undergoing cardiac surgery with CPB.

Methods: Plasma from CAD patients (N = 13) undergoing on-pump coronary arterial bypass graft (CABG) was analyzed using a targeted metabolomics approach for 630 metabolites. The samples were collected one day prior (d0) and on days 1, 3, and 7 postsurgery. Plasma metabolites from d1, d3 and d7 were compared with d0 (baseline).

Results: Compared to d0, there were significant changes in metabolite concentrations on d1 (85 changed metabolites) and d3 (172 metabolites), with noticeable normalization by d7. Notably, the highest degree of change was seen with triglycerides (TG), followed by lysophosphatidylcholines (lysoPC) and bile acids (BA), where the concentrations of these 3 metabolic categories decreased postsurgery, compared to baseline, with TG accounting for >50% reduction at d1 and d3 followed by lysoPC and BA. Further, the duration of CPB showed a strong negative correlation with TG, diglycerides (DG) and phosphatidylcholines (PC). In addition, predicted phospholipase A2 activity was elevated on d7. Importantly, metabolites corresponding to carnitine pathway were significantly reduced on d1 and d7.

Conclusion: Patients exposed to CPB exhibit significant changes in plasma metabolites. Reduced BA and deficit in carnitine system might indicate an ongoing gut dysbiosis. Additionally, increased PLA-2 activity possibly indicates increased vascular inflammation. The duration of CPB correlates with metabolomic changes that may not be driven by inflammation but rather to a catabolic state due to operative stress. Taken together, altered metabolites with deficit in carnitine system could possibly reflect organ dysfunction induced by CPB.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
13 February 2024