dinoprost and Heart-Defects--Congenital

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.. 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.. 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.. Controlled reoxygenation CPB decreased the markers of organ damage, stress, inflammation, and oxidative stress in single-ventricle patients undergoing cardiac surgery.

Topics: Age Factors; Biomarkers; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child; Child, Preschool; Dinoprost; England; Female; Heart Defects, Congenital; Heart Ventricles; Humans; Infant; Inflammation; Inflammation Mediators; Male; Oxidative Stress; Oxygen Inhalation Therapy; Partial Pressure; Time Factors; Treatment Outcome; Troponin

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.. 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.. 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).. 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.

Topics: Cardiopulmonary Bypass; Child, Preschool; Complement C3a; Cyanosis; Dinoprost; Female; Glutathione Transferase; Heart Defects, Congenital; Humans; Hydrocortisone; Infant; Inflammation; Interleukins; Male; Oxidative Stress; Oxygen; S100 Proteins; Troponin I

The purpose of this study is to investigate the effect of cardiopulmonary bypass (CPB) temperature on myocardial reperfusion injury, oxidative stress, and inflammatory response in pediatric open heart surgery.. Fifty-nine children (median age 78 months; interquartile range, 39-130) undergoing correction of simple congenital heart defects were randomized to receive either hypothermic (28 degrees C) or normothermic (35-37 degrees C) CPB. Troponin I and 8-isoprostane, complement activation C3a, interleukin (IL) -6, -8, and -10, were measured preoperatively, on removal of the aortic cross clamp, 30 minutes, 6, and 24 hours postoperatively.. Troponin I and 8-isoprostane were significantly raised, compared to baseline, in both groups, and remained high at 24 hours. Overall, troponin I and 8-isoprostane levels were 37% and 84% higher in the hypothermic than in the normothermic group, respectively (ratio 1.37, 95% CI 1.00 to 1.88, p = 0.053 and 1.84, 95% CI 1.22 to 2.78, p = 0.0045, respectively), and there was no evidence to suggest the treatment effect changed significantly over the time points measured (p = 0.63). Adjusting for aortic cross-clamp time reduced the effect of hypothermia on troponin (p = 0.18) but not on 8-isoprostane levels (p = 0.0028). The C3a, IL-6, and IL-8 release was similar in the two groups. The IL-10 release between the groups changed over time (p = 0.059) and examining differences at individual time points highlighted a statistically significant difference at the end of the cross-clamp time (p = 0.0079).. Normothermic CPB is associated with reduced oxidative stress compared with hypothermic CPB, and similar myocardial reperfusion injury and whole body inflammatory response, in children undergoing open heart surgery. A larger study with clinical outcomes as primary end points is now warranted.

Topics: Biomarkers; Body Temperature; Cardiopulmonary Bypass; Child; Child, Preschool; Dinoprost; Female; Heart Defects, Congenital; Humans; Hypothermia, Induced; Inflammation; Interleukins; Male; Myocardial Reperfusion Injury; Oxidative Stress; Pediatrics; Treatment Outcome; Troponin I

The purpose of this study was to investigate the influence of parental transgenerational genetics and maternal metabolic state on fetal maldevelopment in diabetic rat pregnancy. Rats from an inbred malformation-resistant (W) strain, and an inbred malformation-prone (L) strain, were cross-mated to produce two different F(1) hybrids, WL and LW. Normal (N) and manifestly diabetic (MD) WL and LW females were mated with normal males of the same F(1) generation to obtain WLWL and LWLW F(2) hybrids. Maternal diabetes increased malformation and resorption rates in both F(2) generations. MD-WLWL offspring had higher resorption rate but similar malformation rate compared with the MD-LWLW offspring. Malformed MD-WLWL offspring presented with 100% agnathia/micrognathia, whereas malformed MD-LWL offspring had 60% agnathia/micrognathia and 40% cleft lip and palate. The MD-WL dams showed increased β-hydroxybutyrate levels and alterations in concentrations of several amino acids (taurine, asparagine, citrulline, cystine, glutamic acid, leucine, tyrosine, and tryptophan) compared with MD-LW dams. Fetal glyceraldehyde-3-phosphate dehydrogenase (Gapdh) activity and gene expression were more altered in MD-WLWL than MD-LWLW. Fetal gene expression of reactive oxygen species (ROS) scavenger enzymes was diminished in MD-WLWL compared with MD-LWLW. Glial cell line-derived neurotrophic factor and Ret proto-oncogene gene expression was decreased in both MD-WLWL and MD-LWLW fetuses, whereas increased bone morphogenetic protein 4 and decreased Sonic hedgehog homolog expression was found only in MD-LWLW fetuses. Despite identical autosomal genotypes, the WL and LW dams gave birth to offspring with markedly different malformation patterns. Together with fetal differences in enzymatic activity and expression of Gapdh, ROS scavengers, and developmental genes, these results may suggest a teratological mechanism in diabetic pregnancy influenced by maternal metabolism and parental strain epigenetics.

Topics: Aldehyde Reductase; Amino Acids; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Dinoprost; Epigenesis, Genetic; Female; Gene Expression Regulation, Developmental; Gestational Age; Glyceraldehyde-3-Phosphate Dehydrogenases; Heart Defects, Congenital; Lipids; Male; Mandible; Pregnancy; Pregnancy in Diabetics; Rats; Rats, Inbred WF; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase; Superoxide Dismutase-1