Cardiopulmonary Bypass Reduces Myocardial Oxidative Stress, Inflammation and Increases C-kitCD45 Cell Population in Newborns

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2018 Apr 29

PMID 29703225

Citations 1

Authors

Johannes Petersen

Andrey Kazakov

Michael Bohm

Hans-Joachim Schafers

Ulrich Laufs

Hashim Abdul-Khaliq

Affiliations

Soon will be listed here.

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-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.

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.

Citing Articles

Oxidative Stress and Neonatal Respiratory Extracorporeal Membrane Oxygenation.

Raffaeli G, Ghirardello S, Passera S, Mosca F, Cavallaro G Front Physiol. 2018; 9:1739.

PMID: 30564143 PMC: 6288438. DOI: 10.3389/fphys.2018.01739.

References

Ishigami S, Ohtsuki S, Tarui S, Ousaka D, Eitoku T, Kondo M . Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial. Circ Res. 2014; 116(4):653-64. DOI: 10.1161/CIRCRESAHA.116.304671. View

Ades A, Dominguez T, Nicolson S, Gaynor J, Spray T, Wernovsky G . Morbidity and mortality after surgery for congenital cardiac disease in the infant born with low weight. Cardiol Young. 2009; 20(1):8-17. DOI: 10.1017/S1047951109991909. View

Schwedler G, Lindinger A, Lange P, Sax U, Olchvary J, Peters B . 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. DOI: 10.1007/s00392-011-0355-7. View

Biederman R, Magovern J, Grant S, Williams R, Yamrozik J, Vido D . 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. PMC: 3094375. DOI: 10.1186/1749-8090-6-53. View

Cheng H, Wypij D, Laussen P, Bellinger D, Stopp C, Soul J . Cerebral blood flow velocity and neurodevelopmental outcome in infants undergoing surgery for congenital heart disease. Ann Thorac Surg. 2014; 98(1):125-32. PMC: 4230572. DOI: 10.1016/j.athoracsur.2014.03.035. View

Kikuchi K, Poss K . Cardiac regenerative capacity and mechanisms. Annu Rev Cell Dev Biol. 2012; 28:719-41. PMC: 3586268. DOI: 10.1146/annurev-cellbio-101011-155739. View

Kazakov A, Meier T, Werner C, Hall R, Klemmer B, Korbel C . C-kit(+) resident cardiac stem cells improve left ventricular fibrosis in pressure overload. Stem Cell Res. 2015; 15(3):700-711. DOI: 10.1016/j.scr.2015.10.017. View

Lindinger A, Schwedler G, Hense H . 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. DOI: 10.1055/s-0030-1254155. View

Tarui S, Ishigami S, Ousaka D, Kasahara S, Ohtsuki S, Sano S . 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):1198-1207, 1208.e1-2. DOI: 10.1016/j.jtcvs.2015.06.076. View

10.

Wren C, Richmond S, Donaldson L . Temporal variability in birth prevalence of cardiovascular malformations. Heart. 2000; 83(4):414-9. PMC: 1729354. DOI: 10.1136/heart.83.4.414. View

11.

Caldarone C, Barner E, Wang L, Karimi M, Mascio C, Hammel J . Apoptosis-related mitochondrial dysfunction in the early postoperative neonatal lamb heart. Ann Thorac Surg. 2004; 78(3):948-55. DOI: 10.1016/j.athoracsur.2004.04.031. View

12.

Hesse M, Fleischmann B, Kotlikoff M . 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. DOI: 10.1002/stem.1696. View

13.

Kang N, Cole T, Tsang V, Elliott M, de Leval M . Risk stratification in paediatric open-heart surgery. Eur J Cardiothorac Surg. 2004; 26(1):3-11. DOI: 10.1016/j.ejcts.2004.03.038. View

14.

Dollat C, Vergnat M, Laux D, Stos B, Baruteau A, Capderou A . Critical Congenital Heart Diseases in Preterm Neonates: Is Early Cardiac Surgery Quite Reasonable?. Pediatr Cardiol. 2015; 36(6):1279-86. DOI: 10.1007/s00246-015-1158-9. View

15.

Mahmoud A, Porrello E . Turning back the cardiac regenerative clock: lessons from the neonate. Trends Cardiovasc Med. 2012; 22(5):128-33. DOI: 10.1016/j.tcm.2012.07.008. View

16.

Gilboa S, Salemi J, Nembhard W, Fixler D, Correa A . Mortality resulting from congenital heart disease among children and adults in the United States, 1999 to 2006. Circulation. 2010; 122(22):2254-63. PMC: 4911018. DOI: 10.1161/CIRCULATIONAHA.110.947002. View

17.

Ishigami S, Ohtsuki S, Eitoku T, Ousaka D, Kondo M, Kurita Y . Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease) Randomized Phase 2 Trial. Circ Res. 2017; 120(7):1162-1173. DOI: 10.1161/CIRCRESAHA.116.310253. View

18.

Eckersley L, Sadler L, Parry E, Finucane K, Gentles T . Timing of diagnosis affects mortality in critical congenital heart disease. Arch Dis Child. 2015; 101(6):516-520. DOI: 10.1136/archdischild-2014-307691. View

19.

De Hert S, Moerman A . Myocardial injury and protection related to cardiopulmonary bypass. Best Pract Res Clin Anaesthesiol. 2015; 29(2):137-49. DOI: 10.1016/j.bpa.2015.03.002. View

20.

Veres G, Radovits T, Merkely B, Karck M, Szabo G . Custodiol-N, the novel cardioplegic solution reduces ischemia/reperfusion injury after cardiopulmonary bypass. J Cardiothorac Surg. 2015; 10:27. PMC: 4350983. DOI: 10.1186/s13019-015-0226-9. View