Department of Pediatric Cardiology, Saarland University Medical Center, 66421, Homburg/Saar, Germany.
Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany.
J Transl Med. 2018 Apr 27;16(1):111. doi: 10.1186/s12967-018-1478-7.
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-kitCD45 cells (resident cardiac stem cells) were increased in newborns (2.2 ± 1.9/mm) and decreased in children - 1.5 ± 0.7/mm, 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.
本研究旨在探讨体外循环(CPB)对新生儿和儿童心肌重构的影响。
从 4 名新生儿(5-11 天)和 7 名儿童(8 个月-16 岁)的右心房在 CPB 前后取活检。对 10μm 心脏组织冷冻切片进行免疫染色,以检测 c-kit 细胞、白细胞(CD45 细胞)、Ki67 有丝分裂细胞。通过检测 8-羟基鸟嘌呤(8-dOHG)心肌细胞和非心肌细胞的比例[(8-dOHG)-指数]来量化氧化应激。
新生儿组(2.2±1.9/mm)Δ c-kitCD45 细胞(驻留心脏干细胞)增加,儿童组(-1.5±0.7/mm)减少,p<0.01。新生儿组(8-dOHG)-指数降低 43%,儿童组降低 20%。CPB 不影响心脏细胞更新;新生儿 CPB 前后细胞增殖率高。CPB 显著降低新生儿白细胞浸润率至 40±8%,p<0.05,但对儿童无影响。新生儿心肌中嗜酸性粒细胞(嗜酸性粒细胞/CD45%)浸润完全消失,p<0.05,CPB 后儿童组减少至 22±8%,n.s.
新生儿、较大婴儿和儿童对 CPB 的心肌即刻反应和重构方式不同。与儿童相比,CPB 后新生儿组中表达 c-kit 的 CD45 细胞数量增加。需要在更大的患者队列中进一步评估这种观察的临床价值。