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Controlling Reoxygenation During Cardiopulmonary Bypass is Associated with Reduced Transcriptomic Changes in Cyanotic Patients with Tetralogy of Fallot Undergoing Heart Surgery

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE38177 | GEO | 2012/12/06

SECONDARY ACCESSION(S): PRJNA167334

REPOSITORIES: GEO

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Project description:In cyanotic patients undergoing repair of heart defects, high level of oxygen during cardiopulmonary bypass (CPB) leads to greater susceptibility to myocardial ischemia and reoxygenation injury. This study investigates the effects of controlled reoxygenation CPB on gene expression changes in cyanotic hearts of patients undergoing surgical correction of tetralogy of Fallot (TOF). We randomized 49 cyanotic TOF patients undergoing corrective cardiac surgery to receive either controlled reoxygenation or hyperoxic/standard CPB. Ventricular myocardium biopsies were obtained immediately after starting and before discontinuing CPB. Microarray analyses were performed on samples, and array results validated with real-time PCR. Gene expression profiles before and after hyperoxic/standard CPB revealed 35 differentially expressed genes with three upregulated and 32 downregulated. Upregulated genes included two E3 Ubiquitin ligases. The products of downregulated genes included intracellular signaling kinases, metabolic process proteins, and transport factors. In contrast, gene expression profiles before and after controlled reoxygenation CPB revealed only 11 differentially expressed genes with 10 upregulated including extracellular matrix proteins, transport factors, and one downregulated. The comparison of gene expression following hyperoxic/standard vs. controlled reoxygenation CPB revealed 59 differentially expressed genes, with six upregulated and 53 downregulated. Upregulated genes included PDE1A, MOSC1, and CRIP3. Downregulated genes functionally clustered into four major classes: extracellular matrix/cell adhesion, transcription, transport, and cellular metabolic process. This study provides direct evidence that hyperoxic CPB decreases the adaptation and remodeling capacity in cyanotic patients undergoing TOF repair. This simple CPB strategy of controlled reoxygenation reduced the number of genes whose expression was altered following hyperoxic/standard CPB.

Project description:Unfavorable left ventricular (LV) remodelling may be associated with adverse outcomes after Tetralogy of Fallot (TOF) repair. We sought to assess T1 cardiovascular magnetic resonance (CMR) markers of diffuse LV myocardial fibrosis in children after TOF repair, and associated factors.In this prospective, cross-sectional study, native (=non-contrast) T1 times and extracellular volume fraction (ECV) were quantified in the LV myocardium using CMR. Results were related to ventricular volumes and function, degree of pulmonary regurgitation, as well as surgical characteristics, and exercise capacity.There was no difference in native T1 times or ECV between 31 TOF patients (age at CMR 13.9 ± 2.4 years, 19 male) and 15 controls (age at CMR 13.4 ± 2.6 years, 7 male). Female TOF patients had higher ECVs than males (25.2 ± 2.9 % versus 22.7 ± 3.3 %, p < 0.05). In the patient group, higher native T1 and ECV correlated with higher Z-Scores of right and left ventricular end-diastolic volumes, but not with reduced left and right ventricular ejection fraction or higher pulmonary regurgitation fraction. Longer cardiopulmonary bypass and aortic cross clamp times at surgery correlated with increased native T1 times and ECVs (r = 0.48, p < 0.05 and r = 0.65, p < 0.01, respectively). Maximum workload (percent of predicted for normal) correlated inversely with ECV (r = -0.62, p < 0.05). Higher native T1 times correlated with worse LV longitudinal (r = 0.50, p < 0.05) and mid short axis circumferential strain (r = 0.38, p < 0.05).As compared to controls, TOF patients did not express higher markers of diffuse fibrosis. Longer cardiopulmonary bypass and aortic cross clamp times at surgery as well as biventricular enlargement and reduced exercise tolerance are associated with markers of diffuse myocardial fibrosis after TOF repair. Female patients have higher markers of diffuse myocardial fibrosis than males.

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Controlling Reoxygenation During Cardiopulmonary Bypass is Associated with Reduced Transcriptomic Changes in Cyanotic Patients with Tetralogy of Fallot Undergoing Heart Surgery

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