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Objective: Single-ventricle patients undergoing pediatric heart surgery are a high-risk group owing to reoxygenation injury during cardiopulmonary bypass (CPB). The present study investigated the effects of controlled reoxygenation CPB on biomarkers of organ damage, inflammation, stress, and long-term functional outcomes in cyanotic patients with either a single or double ventricle during open heart surgery., Methods: Cyanotic patients with either a single (n = 32) or double (n = 47) ventricle undergoing surgical correction were randomized to receive CPB using either standard oxygen levels or controlled reoxygenation. The markers of cardiac injury, inflammation, stress, and cerebral and hepatic injury were measured preoperatively, at 10 and 30 minutes after starting CPB, and at 10 minutes and 4 and 24 hours after CPB. The data were analyzed using a mixed regression model., Results: No difference was found in the pre- or intraoperative characteristics between the standard and controlled reoxygenation CPB groups for single- or double-ventricle patients. In the single-ventricle patients, controlled reoxygenation CPB significantly (P < .05) decreased the markers of organ damage, inflammation, stress, and oxidative stress. In contrast, the markers of inflammation and cardiac injury were not altered by controlled reoxygenation CPB in the double-ventricle patients., Conclusions: Controlled reoxygenation CPB decreased the markers of organ damage, stress, inflammation, and oxidative stress in single-ventricle patients undergoing cardiac surgery., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: In cyanotic patients undergoing repair of heart defects, chronic hypoxia is thought to lead to greater susceptibility to ischemia and reoxygenation injury. We sought to find an explanation to such a hypothesis by investigating the cardiac gene expression in patients with tetralogy of Fallot undergoing cardiac surgery., Methods: The myocardial gene profile was investigated in right ventricular biopsy specimens obtained from 20 patients with a diagnosis of cyanotic (n = 11) or acyanotic (n = 9) tetralogy of Fallot undergoing surgical repair. Oligonucleotide microarray analyses were performed on the samples, and the array results were validated with Western blotting and enzyme-linked immunosorbent assay., Results: Data revealed 795 differentially expressed genes in cyanotic versus acyanotic hearts, with 198 upregulated and 597 downregulated. Growth/morphogenesis, remodeling, and apoptosis emerged as dominant functional themes for the upregulated genes and included the apoptotic gene TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), the remodeling factor OPN (osteopontin), and the mitochondrial function gene COX11 (cytochrome-c oxidase 11). In contrast, transcription, mitogen-activated protein kinase signaling, and contractile machinery were the dominant functional classes for the downregulated genes, which included the calcium-handling gene NCX1 (sodium-calcium exchanger). Protein levels of COX11, NCX1, OPN, and LYZ (lysozyme) in the myocardium followed the same pattern obtained by means of transcriptomics. The TRAIL level did not change in myocardium but increased in circulating blood of cyanotic patients, suggesting the myocardium as a possible source. Additionally, our data showed increased protein expression of apoptosis markers in cyanotic myocardium., Conclusions: Chronic hypoxia in cyanotic children with tetralogy of Fallot induced the expression of genes associated with apoptosis and remodeling and reduced the expression of genes associated with myocardium contractility and function., (Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: This study investigates the effects of controlled reoxygenation cardiopulmonary bypass on oxidative stress, inflammatory response, and organ function in children undergoing repair of cyanotic congenital heart defects., Methods: Sixty-seven cyanotic patients (median age 15 months, interquartile range 6-49 months) undergoing corrective cardiac surgery were randomized to receive either controlled normoxic (50-0 mm Hg; n = 35) or hyperoxic (150-180 mm Hg; n = 32) cardiopulmonary bypass. Troponin I and 8-isoprostane, C3a, interleukins 6, 8, and 10, cortisol, protein S100, and alpha-glutamate transferase were measured preoperatively and 10 and 30 minutes after starting bypass, on removal of the aortic crossclamp, and 12 and 24 hours thereafter., Results: Overall, troponin I and 8-isoprostane levels were lower in the controlled normoxic group (-29%, 95% CI -48% to -3%, P = .03, and -26%, 95% CI -44% to -2%, P = .03, respectively). Protein S100 release was also lower in the normoxic group 10 minutes after starting bypass (-26%, 95% CI -40% to -9%, P = .005) and 10 minutes after aortic crossclamp removal (-23%, 95% CI -38% to -3%, P = .02, respectively), but similar at other time points in the two groups (P >or= .17). The alpha-glutamate transferase release was significantly lower in the normoxic group 10 minutes after aortic crossclamp removal (-28%, 95% CI -44% to -9%, P = .006, respectively) but was similar at other times (P >or= .11). Release of C3a, interleukins 6, 8, and 10, and cortisol was similar in the two groups throughout (P >or= .15)., Conclusion: Controlled reoxygenation on starting cardiopulmonary bypass is associated with reduced myocardial damage, oxidative stress, and cerebral and hepatic injury compared with hyperoxic bypass and similar whole body inflammatory and stress response in cyanotic children undergoing open cardiac surgery.