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Cardiopulmonary bypass with deep hypothermic circulatory arrest results in organ-specific transcriptomic responses in pediatric swine

ABSTRACT: Cardiopulmonary bypass with deep hypothermic circulatory arrest results in organ-specific transcriptomic responses in pediatric swine

PROVIDER: PRJNA1250478 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33134000_1.fastq.gz	Fastqsanger.gz
	SRR33134000_2.fastq.gz	Fastqsanger.gz
	SRR33134100_1.fastq.gz	Fastqsanger.gz
	SRR33134100_2.fastq.gz	Fastqsanger.gz
	SRR33134001_1.fastq.gz	Fastqsanger.gz

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Cardiopulmonary bypass with deep hypothermic circulatory arrest results in organ-specific transcriptomic responses in pediatric swine

Project description: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.

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Project description:The purpose of this study was to detect the expression profile of tsRNA during deep hypothermia circulatory arrest, and to find possible regulatory factors according to the changes in its expression level, in the hope of providing an effective organ protection strategy for this process.Three blood samples were collected from a central veins line into ethylenediaminetetraacetic acid (EDTA) tubes as follows: T1 (before starting circulatory arrest), T2 (15 min after initiation of DHCA), T3 (after declamping the left common carotid artery and before rewarming). A total of 286 commonly expressed tsRNAs were identified in the T1 and T2 groups, 68 tsRNAs specifically expressed in the T1 group, and 44 tsRNAs specifically expressed in the T2 group. A total of 290 commonly expressed tsRNAs were identified in the T2 and T3 groups, 64 tsRNAs specifically expressed in the T2 group, and 43 tsRNAs specifically expressed in the T3 group. Next, four tsRNAs were selected to be verified by qRT-PCR. In summary, this study innovatively proposed the correlation between the deep hypothermic circulatory arrest process and the expression profile of tsRNA, and evaluated the expression level and regulation mode of tsRNA. A preliminary exploration of its potential biological role in the process of deep hypothermic circulatory arrest has been carried out, which can provide a better basis and a more comprehensive explanation for the organ protection mechanism of deep hypothermic circulatory arrest. And in further research, we are expected to achieve targeted protection of organs by overexpressing or inhibiting the corresponding tsRNA.

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Project description:To investigate changes in cardiac transcription profiles caused by on-pump cardiac surgery, we collected myocardial samples, prior and after grafting, from patients undergoing on-pump coronary artery bypass grafting with cardiopulmonary bypass and cardiac arrest. The transcriptional profile of the mRNA in these samples was measured with gene array technology. Changes in transcriptional profiles can be correlated with the stress response of heart to surgery, cardiopulmonary bypass and cardiac arrest. Keywords: human, cardiac, CABG coronary surgery, gene expression, cardiopulmonary bypass. Myocardial samples were collected, prior and after grafting, from patients undergoing on-pump coronary artery bypass grafting with cardiopulmonary bypass and cardiac arrest.

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