Whole blood transcriptomics reveals granulocyte colony-stimulating factor as a mediator of cardiopulmonary bypass-induced systemic inflammatory response syndrome.

Objectives: Systemic inflammatory response syndrome (SIRS) is a frequent complication of cardiopulmonary bypass (CPB). SIRS is associated with significant morbidity and mortality, but its pathogenesis remains incompletely understood, and as a result, biomarkers are lacking and treatment remains expectant and supportive. This study aimed to understand the pathophysiological mechanisms driving SIRS induced by CPB and identify novel therapeutic targets that might reduce systemic inflammation and improve patient outcomes. Methods: Twenty-one patients undergoing cardiac surgery and CPB were recruited, and blood was sampled before, during and after surgery. SIRS was defined using the American College of Chest Physicians/Society of Critical Care Medicine criteria. We performed immune cell profiling and whole blood transcriptomics and measured individual mediators in plasma/serum to characterise SIRS induced by CPB. Results: Nineteen patients fulfilled criteria for SIRS, with a mean duration of 2.7 days. Neutrophil numbers rose rapidly with CPB and remained elevated for at least 48 h afterwards. Transcriptional signatures associated with neutrophil activation and degranulation were enriched during CPB. We identified a network of cytokines governing these transcriptional changes, including granulocyte colony-stimulating factor (G-CSF), a regulator of neutrophil production and function. Conclusions: We identified neutrophils and G-CSF as major regulators of CPB-induced systemic inflammation. Short-term targeting of G-CSF could provide a novel therapeutic strategy to limit neutrophil-mediated inflammation and tissue damage in SIRS induced by CPB.

Comparing the patency of the left internal mammary in single, sequential, and Y grafts.

BACKGROUND: To maximize arterial grafts, left internal mammary (LIMA) sequential and Y grafts are used. The aim is to compare the angiographic patency of the LIMA in these configurations. METHODS: Between 2002 and 2020, angiography was performed on 1000 patients who either had a single (570), sequential (100), or LIMA y (129) graft. The LIMA was divided into segments (S); S1: LIMA inflow to the first anastomosis, S2: terminal portion of the LIMA to left anterior descending (LAD), and S3; the y-limb anastomosis to a coronary. S1 and S2 patency analysis was carried out with logistic regression. RESULTS: Failure of the S1 and S2 was 3.7% single, 9% sequential, and 6.2 Y graft (P = .049). Segment 1 failed in 3.7% in single, 5% in sequential, and 0.8% in Y grafts (P = .049). Segment 3 failure was 10.3%. Regression revealed female sex and sequential grafts were associated with decreased S1 and S2 patency. CONCLUSIONS: Single grafts have the best patency. Failure in sequential grafts leads to increased occlusion of the LIMA inflow, whereas Y-graft failure tends to occlude the y limb. When arterial conduit is sparse, a Y graft should be considered.