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Published in: Journal of Translational Medicine 1/2018

Open Access 01-12-2018 | Research

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

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

Published in: Journal of Translational Medicine | Issue 1/2018

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Abstract

Background

The aim of this study was to characterize the influence of cardiopulmonary bypass (CPB) on myocardial remodeling in newborns and children.

Methods

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.

Results

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.

Conclusions

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.
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Literature
2.
go back to reference Eckersley L, et al. Timing of diagnosis affects mortality in critical congenital heart disease. Arch Dis Child. 2016;101(6):516–20.CrossRefPubMed Eckersley L, et al. Timing of diagnosis affects mortality in critical congenital heart disease. Arch Dis Child. 2016;101(6):516–20.CrossRefPubMed
3.
go back to reference van der Linde D, et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58(21):2241–7.CrossRefPubMed van der Linde D, et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58(21):2241–7.CrossRefPubMed
4.
go back to reference Lindinger A, Schwedler G, Hense HW. Prevalence of congenital heart defects in newborns in Germany: results of the first registration year of the PAN Study (July 2006 to June 2007). Klin Padiatr. 2010;222(5):321–6.CrossRefPubMed Lindinger A, Schwedler G, Hense HW. Prevalence of congenital heart defects in newborns in Germany: results of the first registration year of the PAN Study (July 2006 to June 2007). Klin Padiatr. 2010;222(5):321–6.CrossRefPubMed
5.
go back to reference Schwedler G, et al. Frequency and spectrum of congenital heart defects among live births in Germany: a study of the Competence Network for Congenital Heart Defects. Clin Res Cardiol. 2011;100(12):1111–7.CrossRefPubMed Schwedler G, et al. Frequency and spectrum of congenital heart defects among live births in Germany: a study of the Competence Network for Congenital Heart Defects. Clin Res Cardiol. 2011;100(12):1111–7.CrossRefPubMed
6.
go back to reference Gilboa SM, et al. Mortality resulting from congenital heart disease among children and adults in the United States, 1999 to 2006. Circulation. 2010;122(22):2254–63.CrossRefPubMedPubMedCentral Gilboa SM, et al. Mortality resulting from congenital heart disease among children and adults in the United States, 1999 to 2006. Circulation. 2010;122(22):2254–63.CrossRefPubMedPubMedCentral
7.
go back to reference Raissadati A, et al. Progress in late results among pediatric cardiac surgery patients: a population-based 6-decade study with 98% follow-up. Circulation. 2015;131(4):347–53 (discussion 353).CrossRefPubMed Raissadati A, et al. Progress in late results among pediatric cardiac surgery patients: a population-based 6-decade study with 98% follow-up. Circulation. 2015;131(4):347–53 (discussion 353).CrossRefPubMed
8.
go back to reference Erikssen G, et al. Achievements in congenital heart defect surgery: a prospective, 40-year study of 7038 patients. Circulation. 2015;131(4):337–46 (discussion 346).CrossRefPubMed Erikssen G, et al. Achievements in congenital heart defect surgery: a prospective, 40-year study of 7038 patients. Circulation. 2015;131(4):337–46 (discussion 346).CrossRefPubMed
9.
go back to reference Kumar TK, et al. Timing of neonatal cardiac surgery is not associated with perioperative outcomes. J Thorac Cardiovasc Surg. 2014;147(5):1573–9.CrossRefPubMed Kumar TK, et al. Timing of neonatal cardiac surgery is not associated with perioperative outcomes. J Thorac Cardiovasc Surg. 2014;147(5):1573–9.CrossRefPubMed
10.
go back to reference Dollat C, et al. Critical congenital heart diseases in preterm neonates: is early cardiac surgery quite reasonable? Pediatr Cardiol. 2015;36(6):1279–86.CrossRefPubMed Dollat C, et al. Critical congenital heart diseases in preterm neonates: is early cardiac surgery quite reasonable? Pediatr Cardiol. 2015;36(6):1279–86.CrossRefPubMed
11.
go back to reference Ades AM, et al. Morbidity and mortality after surgery for congenital cardiac disease in the infant born with low weight. Cardiol Young. 2010;20(1):8–17.CrossRefPubMed Ades AM, et al. Morbidity and mortality after surgery for congenital cardiac disease in the infant born with low weight. Cardiol Young. 2010;20(1):8–17.CrossRefPubMed
12.
go back to reference Kang N, et al. Risk stratification in paediatric open-heart surgery. Eur J Cardiothorac Surg. 2004;26(1):3–11.CrossRefPubMed Kang N, et al. Risk stratification in paediatric open-heart surgery. Eur J Cardiothorac Surg. 2004;26(1):3–11.CrossRefPubMed
13.
go back to reference Cheng HH, et al. Cerebral blood flow velocity and neurodevelopmental outcome in infants undergoing surgery for congenital heart disease. Ann Thorac Surg. 2014;98(1):125–32.CrossRefPubMedPubMedCentral Cheng HH, et al. Cerebral blood flow velocity and neurodevelopmental outcome in infants undergoing surgery for congenital heart disease. Ann Thorac Surg. 2014;98(1):125–32.CrossRefPubMedPubMedCentral
14.
go back to reference Veres G, et al. Custodiol-N, the novel cardioplegic solution reduces ischemia/reperfusion injury after cardiopulmonary bypass. J Cardiothorac Surg. 2015;10:27.CrossRefPubMedPubMedCentral Veres G, et al. Custodiol-N, the novel cardioplegic solution reduces ischemia/reperfusion injury after cardiopulmonary bypass. J Cardiothorac Surg. 2015;10:27.CrossRefPubMedPubMedCentral
15.
go back to reference De Hert S, Moerman A. Myocardial injury and protection related to cardiopulmonary bypass. Best Pract Res Clin Anaesthesiol. 2015;29(2):137–49.CrossRefPubMed De Hert S, Moerman A. Myocardial injury and protection related to cardiopulmonary bypass. Best Pract Res Clin Anaesthesiol. 2015;29(2):137–49.CrossRefPubMed
16.
18.
19.
go back to reference Mahmoud AI, Porrello ER. Turning back the cardiac regenerative clock: lessons from the neonate. Trends Cardiovasc Med. 2012;22(5):128–33.CrossRefPubMed Mahmoud AI, Porrello ER. Turning back the cardiac regenerative clock: lessons from the neonate. Trends Cardiovasc Med. 2012;22(5):128–33.CrossRefPubMed
21.
go back to reference Lorell BH, Carabello BA. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation. 2000;102(4):470–9.CrossRefPubMed Lorell BH, Carabello BA. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation. 2000;102(4):470–9.CrossRefPubMed
22.
go back to reference Christakis GT, et al. Left ventricular mass regression early after aortic valve replacement. Ann Thorac Surg. 1996;62(4):1084–9.CrossRefPubMed Christakis GT, et al. Left ventricular mass regression early after aortic valve replacement. Ann Thorac Surg. 1996;62(4):1084–9.CrossRefPubMed
23.
go back to reference Biederman RW, et al. LV reverse remodeling imparted by aortic valve replacement for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the American Heart Association. J Cardiothorac Surg. 2011;6:53.CrossRefPubMedPubMedCentral Biederman RW, et al. LV reverse remodeling imparted by aortic valve replacement for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the American Heart Association. J Cardiothorac Surg. 2011;6:53.CrossRefPubMedPubMedCentral
24.
go back to reference Caldarone CA, et al. Apoptosis-related mitochondrial dysfunction in the early postoperative neonatal lamb heart. Ann Thorac Surg. 2004;78(3):948–55.CrossRefPubMed Caldarone CA, et al. Apoptosis-related mitochondrial dysfunction in the early postoperative neonatal lamb heart. Ann Thorac Surg. 2004;78(3):948–55.CrossRefPubMed
25.
go back to reference Karimi M, et al. Neonatal vulnerability to ischemia and reperfusion: cardioplegic arrest causes greater myocardial apoptosis in neonatal lambs than in mature lambs. J Thorac Cardiovasc Surg. 2004;127(2):490–7.CrossRefPubMed Karimi M, et al. Neonatal vulnerability to ischemia and reperfusion: cardioplegic arrest causes greater myocardial apoptosis in neonatal lambs than in mature lambs. J Thorac Cardiovasc Surg. 2004;127(2):490–7.CrossRefPubMed
26.
27.
go back to reference Abu-Halima M, et al. Differential expression of microRNAs following cardiopulmonary bypass in children with congenital heart diseases. J Transl Med. 2017;15(1):117.CrossRefPubMedPubMedCentral Abu-Halima M, et al. Differential expression of microRNAs following cardiopulmonary bypass in children with congenital heart diseases. J Transl Med. 2017;15(1):117.CrossRefPubMedPubMedCentral
28.
go back to reference Hesse M, Fleischmann BK, Kotlikoff MI. Concise review: the role of C-kit expressing cells in heart repair at the neonatal and adult stage. Stem Cells. 2014;32(7):1701–12.CrossRefPubMed Hesse M, Fleischmann BK, Kotlikoff MI. Concise review: the role of C-kit expressing cells in heart repair at the neonatal and adult stage. Stem Cells. 2014;32(7):1701–12.CrossRefPubMed
29.
go back to reference Kazakov A, et al. C-kit(+) resident cardiac stem cells improve left ventricular fibrosis in pressure overload. Stem Cell Res. 2015;15(3):700–11.CrossRefPubMed Kazakov A, et al. C-kit(+) resident cardiac stem cells improve left ventricular fibrosis in pressure overload. Stem Cell Res. 2015;15(3):700–11.CrossRefPubMed
30.
go back to reference Avolio E, et al. Expansion and characterization of neonatal cardiac pericytes provides a novel cellular option for tissue engineering in congenital heart disease. J Am Heart Assoc. 2015;4(6):e002043.CrossRefPubMedPubMedCentral Avolio E, et al. Expansion and characterization of neonatal cardiac pericytes provides a novel cellular option for tissue engineering in congenital heart disease. J Am Heart Assoc. 2015;4(6):e002043.CrossRefPubMedPubMedCentral
31.
go back to reference Ishigami S, et al. Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial. Circ Res. 2015;116(4):653–64.CrossRefPubMed Ishigami S, et al. Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial. Circ Res. 2015;116(4):653–64.CrossRefPubMed
32.
go back to reference Ishigami S, et al. Intracoronary cardiac progenitor cells in single ventricle physiology: the PERSEUS (cardiac progenitor cell infusion to treat uni-ventricular heart disease) randomized phase 2 trial. Circ Res. 2017;120(7):1162–73.CrossRefPubMed Ishigami S, et al. Intracoronary cardiac progenitor cells in single ventricle physiology: the PERSEUS (cardiac progenitor cell infusion to treat uni-ventricular heart disease) randomized phase 2 trial. Circ Res. 2017;120(7):1162–73.CrossRefPubMed
33.
go back to reference Tarui S, et al. Transcoronary infusion of cardiac progenitor cells in hypoplastic left heart syndrome: three-year follow-up of the transcoronary infusion of cardiac progenitor cells in patients with single-ventricle physiology (TICAP) trial. J Thorac Cardiovasc Surg. 2015;150(5):1198–207.CrossRefPubMed Tarui S, et al. Transcoronary infusion of cardiac progenitor cells in hypoplastic left heart syndrome: three-year follow-up of the transcoronary infusion of cardiac progenitor cells in patients with single-ventricle physiology (TICAP) trial. J Thorac Cardiovasc Surg. 2015;150(5):1198–207.CrossRefPubMed
Metadata
Title
Cardiopulmonary bypass reduces myocardial oxidative stress, inflammation and increases c-kit+CD45− cell population in newborns
Authors
Johannes Petersen
Andrey Kazakov
Michael Böhm
Hans-Joachim Schäfers
Ulrich Laufs
Hashim Abdul-Khaliq
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-018-1478-7

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