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J Cardiovasc Dev Dis. 2019 Dec 18;7(1). doi: 10.3390/jcdd7010001.

Scar Formation with Decreased Cardiac Function Following Ischemia/Reperfusion Injury in 1 Month Old Swine.

Journal of cardiovascular development and disease

Emma J Agnew, Nivedhitha Velayutham, Gabriela Matos Ortiz, Christina M Alfieri, Luis Hortells, Victoria Moore, Kyle W Riggs, R Scott Baker, Aaron M Gibson, Sithara Raju Ponny, Tarek Alsaied, Farhan Zafar, Katherine E Yutzey

Affiliations

  1. Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA.
  2. Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.
  3. Division of Pediatric Cardiothoracic Surgery, The Heart Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
  4. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.

PMID: 31861331 PMCID: PMC7151069 DOI: 10.3390/jcdd7010001

Abstract

Studies in mice show a brief neonatal period of cardiac regeneration with minimal scar formation, but less is known about reparative mechanisms in large mammals. A transient cardiac injury approach (ischemia/reperfusion, IR) was used in weaned postnatal day (P)30 pigs to assess regenerative repair in young large mammals at a stage when cardiomyocyte (CM) mitotic activity is still detected. Female and male P30 pigs were subjected to cardiac ischemia (1 h) by occlusion of the left anterior descending artery followed by reperfusion, or to a sham operation. Following IR, myocardial damage occurred, with cardiac ejection fraction significantly decreased 2 h post-ischemia. No improvement or worsening of cardiac function to the 4 week study end-point was observed. Histology demonstrated CM cell cycling, detectable by phospho-histone H3 staining, at 2 months of age in multinucleated CMs in both sham-operated and IR pigs. Inflammation and regional scar formation in the epicardial region proximal to injury were observed 4 weeks post-IR. Thus, pigs subjected to cardiac IR at P30 show myocardial damage with a prolonged decrease in cardiac function, formation of a regional scar, and increased inflammation, but do not regenerate myocardium even in the presence of CM mitotic activity.

Keywords: cardiac function; cardiomyocyte; cell cycling; ischemia/reperfusion injury; swine

References

  1. J Mol Cell Cardiol. 2016 Feb;91:23-7 - PubMed
  2. Development. 2016 Mar 1;143(5):729-40 - PubMed
  3. Circulation. 2013 Dec 24;128(25):2764-75 - PubMed
  4. Science. 2011 Feb 25;331(6020):1078-80 - PubMed
  5. Circ Res. 2017 Nov 10;121(11):1263-1278 - PubMed
  6. Circulation. 2018 Dec 11;138(24):2798-2808 - PubMed
  7. Cardiovasc Revasc Med. 2016 Jun;17(4):262-71 - PubMed
  8. Nature. 2017 Jan 12;541(7636):222-227 - PubMed
  9. Circulation. 2018 Dec 11;138(24):2817-2819 - PubMed
  10. Am J Physiol. 1996 Nov;271(5 Pt 2):H2183-9 - PubMed
  11. Nature. 2019 May;569(7756):418-422 - PubMed
  12. Aging (Albany NY). 2012 Dec;4(12):966-77 - PubMed
  13. Cell Mol Life Sci. 2019 Apr;76(7):1365-1380 - PubMed
  14. Am J Physiol Heart Circ Physiol. 2019 Aug 1;317(2):H345-H356 - PubMed
  15. Circ Res. 2011 Dec 9;109(12):1396-400 - PubMed
  16. Nature. 2013 Jan 17;493(7432):433-6 - PubMed
  17. Pediatr Cardiol. 2019 Oct;40(7):1345-1358 - PubMed
  18. J Am Heart Assoc. 2015 Mar 31;4(4): - PubMed
  19. Circulation. 2017 Sep 19;136(12):1123-1139 - PubMed
  20. Comp Med. 2011 Oct;61(5):445-52 - PubMed
  21. JACC Basic Transl Sci. 2017 Dec 25;2(6):669-683 - PubMed
  22. Nat Genet. 2017 Sep;49(9):1346-1353 - PubMed
  23. Bioinformatics. 2014 Aug 1;30(15):2114-20 - PubMed
  24. Nat Biotechnol. 2016 May;34(5):525-7 - PubMed
  25. Circ Res. 2013 Jan 18;112(2):267-77 - PubMed
  26. J Clin Invest. 2011 May;121(5):1894-904 - PubMed
  27. Sci Adv. 2018 May 02;4(5):eaao5553 - PubMed
  28. Circulation. 2018 Dec 11;138(24):2809-2816 - PubMed
  29. Clin Transl Sci. 2012 Oct;5(5):416-21 - PubMed
  30. Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):187-92 - PubMed
  31. J Mol Cell Cardiol. 1996 Aug;28(8):1737-46 - PubMed
  32. Nat Biotechnol. 2014 Sep;32(9):896-902 - PubMed
  33. Nat Rev Cardiol. 2018 Oct;15(10):585-600 - PubMed
  34. Biomed Res Int. 2015;2015:209315 - PubMed
  35. Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11 - PubMed

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