Cardiopulmonary bypass reduces myocardial oxidative stress, inflammation and increases c-kit+CD45− cell population in newborns

Johannes Petersen, Andrey Kazakov, Michael Böhm, Hans-Joachim Schäfers, Ulrich Laufs, Hashim Abdul-Khaliq

The aim of this study was to characterize the influence of cardiopulmonary bypass (CPB) on myocardial remodeling in newborns and children. Biopsies from the right atrium were taken before and after CPB from 4 newborns (5-11 days old) and 7 children (8 months-16 years old). Immunostainings on 10 µm heart tissue frozen sections were performed to detect c-kit+ cells, leukocytes (CD45+ cells), Ki67+ cycling cells. The percentage of 8-hydroxy-guanosine (8-dOHG)+cardiomyocytes and non-cardiomyocytes [(8-dOHG)+-index] were determined to quantify oxidative stress. Δ c-kit+CD45- cells (resident cardiac stem cells) were increased in newborns (2.2 ± 1.9/mm2) and decreased in children - 1.5 ± 0.7/mm2, p < 0.01. The (8-dOHG)+-index was reduced by 43% in newborns and by 20% in children. CPB did not influence cardiac cell turnover; high cell proliferation was seen in newborns before and after CPB. Cardiopulmonary bypass significantly decreased the leucocyte infiltration in newborns to 40 ± 8%, p < 0.05, but not in children. Infiltration with eosinophils (eosinophils/CD45%) was completely abolished in the myocardium of newborns p < 0.05 and reduced to 22 ± 8% in children after CPB, n.s. Immediate response and remodeling of the myocardium to CPB differs between newborns, older infants and children. Especially an increased number of c-kit expressing CD45 cells after CPB were seen in neonates in comparison to children. The clinical value of such observation needs to be further assessed in larger cohorts of patients.