Tumor necrosis factor-alpha in plasma during cardiopulmonary bypass in a pig model: Correlation with marginated neutrophils and cerebral edema by magnetic resonance imaging

Tumor necrosis factor (TNFα) initiates the cytokine cascade via the nuclear factor (NFκB), increasing vascular permeability, inflammation, and edema during and after cardiopulmonary bypass (CPB). Cerebral edema before and after thoracotomy and CPB was evaluated by magnetic resonance imaging. TNF-α in plasma was measured in 12 Yorkshire pigs with an enzyme linked immunosorbent assay technique using a monoclonal antibody made against porcine TNFα. Blood samples were taken 30 min before and 1, 30, 60, 90, 120, 150, and 180 min after initiation of CPB. Plasma was separated from packed cells after centrifugation, and frozen at -80°C. The level of TNFα, measured by color intensity, was read with a 96 well microtiter plate reader. Normal values in plasma were low (range, 0-17 pg/ml; mean, 4.7 pg/ml). In sham control pigs undergoing sternotomy, and pigs that had undergone CBP, TNFα reached a peak value at 120-150 min, and subsequently declined. TNFα in plasma increased in pigs that underwent thoracotomy and CPB. The increase was significantly higher in pigs that underwent CPB. Neutrophil mapping in the pig brain with ¹¹¹In-labeled autologous neutrophils 180 min after CPB, suggested almost uniform distribution and accounted for the 0.02% of total circulating neutrophils in the brain, corresponding to a total of 8 x 10⁵ neutrophils. Magnetic resonance imaging of the pig brain indicated the presence of cerebral edema after CPB, as depicted by the loss of structural details of the sulci, gyri, and ventricles. Activated neutrophils, monocytes, and other inflammatory cells may induce multi-organ edema and injury via TNFα and other regional cytokines.