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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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Transcriptional profiling of pig striatum after deep hypothermic cardiac arrest

Project description:The goal of the study was to identify the gene changes that occur in the striatum of neonatal piglets exposed to cardiopulmonary bypass (CPB) with deep hypothermic cardiac arrest (DHCA) then recovered for 6h. To accomplish our goal, mRNA-seq was performed on RNA isolated from neonatal pigs exposed to either DHCA or sham conditions.

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Project description:heart from rats exposed to cardiopulmonary bypass (CPB) vs sham-operated controls Keywords: other

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Differential expression profiles and functional prediction of tRNA-derived small RNAs in plasma of patients with aortic dissection during deep hypothermic circulatory arrest

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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Alkaline Phosphatase Treatment of Acute Kidney Injury in an Infant Piglet Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest.

Project description:Acute kidney injury (AKI) is associated with prolonged hospitalization and mortality following infant cardiac surgery, but therapeutic options are limited. Alkaline phosphatase (AP) infusion reduced AKI in phase 2 sepsis trials but has not been evaluated for cardiac surgery-induced AKI. We developed a porcine model of infant cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest (DHCA) to investigate post-CPB/DHCA AKI, measure serum/renal tissue AP activity with escalating doses of AP infusion, and provide preliminary assessment of AP infusion for prevention of AKI. Infant pigs underwent CPB with DHCA followed by survival for 4 h. Groups were treated with escalating doses of bovine intestinal AP (1, 5, or 25U/kg/hr). Anesthesia controls were mechanically ventilated for 7 h without CPB. CPB/DHCA animals demonstrated histologic and biomarker evidence of AKI as well as decreased serum and renal tissue AP compared to anesthesia controls. Only high dose AP infusion significantly increased serum or renal tissue AP activity. Preliminary efficacy evaluation demonstrated a trend towards decreased AKI in the high dose AP group. The results of this dose-finding study indicate that AP infusion at the dose of 25U/kg/hr corrects serum and tissue AP deficiency and may prevent AKI in this piglet model of infant CPB/DHCA.

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