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Assessing Vascularization of the Heart of Young Pigs After Cardiac Injury by Ischemia/ Reperfusion
Author(s) -
Matos-Ortiz Gabriela Nicole,
Agnew Emma,
Velayutham Nivedhitha,
Moore Victoria,
Riggs Kyle W.,
Baker Richard Scott,
Alsaied Tarek,
Zafar Farhan,
Yutzey Katherine E.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04410
Subject(s) - ischemia , regeneration (biology) , reperfusion injury , medicine , perfusion , immunohistochemistry , artery , h&e stain , pathology , biology , anatomy , cardiology , microbiology and biotechnology
Existing studies in axolotls, river fish, zebrafish and newts demonstrate that the heart has the capacity to self‐repair following injury, with an increase in existing cardiomyocyte proliferation (CM). Studies on neonatal mice show that the heart can repair during the first week of life following injury, suggesting mammals have a transient window of cardiac regenerative capacity. However, how these findings extend to large mammals remains poorly understood. Recent findings from our laboratory show CM cell‐cycling activity occurring up to 2‐months of age in pigs. This suggests large mammals may have an elongated capacity of heart regeneration compared with previously studied organisms. To assess regeneration after injury, we generated a large mammalian heart injury model. Eight postnatal 30‐day (P30) old pigs underwent ischemia (1hr)/ reperfusion (IR) injury via occlusion of the second diagonal branch of the left anterior descending artery (LAD) and controls underwent sham surgery. We hypothesized that blood vessel density would increase as an effort to normalize blood perfusion to the heart after injury. Tissue harvest occurred 4 weeks after injury and subsequent histochemical analyses were performed within 3 specific zones (scar, border, remote) to assess cell cycling, scar formation, and vessel density. Similar patterns of cell‐cycling activity, measured via pHH3 immunohistochemistry, were found between sham and IR models. Vessel density, as measured via lectin‐DAB staining, was also similar between sham and IR pigs; suggesting no evidence of new blood vessel formation after injury. Collagen deposition, suggestive of scar formation, was evident following injury in IR pigs. This novel approach in assessing cardiac repair following injury in young large mammals highlights that scar formation, rather than an alteration in cardiomyocyte proliferation, might be hindering cardiac regeneration in P30 pigs. Hence, targeting scar formation to understand heart repair mechanisms in young pigs might provide a better understanding of the self‐repair capability of the heart, with potential translation to human systems. Support or Funding Information SURF‐American Heart Association Research Funding, Cincinnati Children’s Hospital Medical Center Research Foundation, Schmidlapp Young Women Scholarship