Cardiopulmonary bypass with deep hypothermic circulatory arrest results in organ-specific transcriptomic responses in pediatric swine
The organ-level molecular response to cardiac surgery with cardiopulmonary bypass (CPB) remains inadequately understood and may be heterogeneous. Here, we measured organ-specific gene expression in a piglet model of CPB with deep hypothermic circulatory arrest (DHCA). Infant piglets underwent peripheral CPB with 75 min of DHCA and 6 h of critical care after separation from CPB. Mechanically ventilated animals served as controls. Tissue was obtained from the lung, kidney, liver, heart, and ileum. RNA sequencing was performed using NovaSeq 6000 and evaluated via differentially expressed gene (DEG) and pathway/network analyses. CPB/DHCA induced significant transcriptomic alterations, with greater changes seen in liver (2,166 DEGs), heart (775 DEGs), and kidney (1,759 DEGs) compared to lung (401 DEGs) and ileum (11 DEGs), and little overlap across organs (<20 % differentially expressed in >1 organ). Key upregulated systems included ribosomal proliferation and mitochondrial assembly in the liver, oxidative stress response and proximal tubular repair in the kidney, myofilament structural genes and pro-hypertrophy pathways in the heart, and solute channels and arginine metabolism in the lung. Downregulation of adaptive immunity genes occurred in multiple organs. Transcriptomics could inform the investigation of targeted therapies and adverse event screening after cardiac surgery. Overall design: Infant swine model with 8 animals serving as anesthesiology controls, 7 animals who underwent CPB/DHCA with no treatment and 4 animals who underwent CPB/DHCA and were administered the drug Linrodostat (75 mg). For animals undergoing CPB/DHCA the circulatory arrest time was 75 minutes.