Abstract 131: Cardiomyocyte Renewal and Cardiac Outcomes Following Injury in Young Swine
| العنوان: | Abstract 131: Cardiomyocyte Renewal and Cardiac Outcomes Following Injury in Young Swine |
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| المؤلفون: | Emma J Agnew, Nivedhitha Velayutham, Victoria Moore, Richard S Baker, Tarek Alsaied, Farhan Zafar, Kyle W. Riggs, Katherine E. Yutzey |
| المصدر: | Circulation Research. 125 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Physiology, Cardiology and Cardiovascular Medicine |
| الوصف: | Objective: Infants with severe congenital heart defects (CHD) typically require lifesaving cardiac surgery. Performing this surgery during a time when the myocardium can proliferate and repair could improve successful outcomes. The mouse heart can regenerate in the first week post-partum, but the mitotic activity of cardiomyocytes (CM) is extended to 1-2-months post-partum in the pig. Thus, the regulation of CM cell cycling ability and renewal in the hearts of young large mammals after injury was examined. Methods & Results: Pigs at postnatal day 30 (n=6) were subjected to cardiac ischemia (1-hour) by temporary occlusion of the left anterior descending (LAD) artery followed by reperfusion (IR), or to sham operation (n=6, no LAD occlusion). LAD occlusion, below the second diagonal branch, provided an effective injury as indicated by increased circulating cardiac troponin-I 2-hours after injury. In addition, ejection fraction (EF) decreased by 46% (57% to 31%) at 2 hours post-ischemia, which was then maintained to the 4-week study end point. Pigs were sacrificed 4 weeks after surgery and histology demonstrated evidence of scar formation in the area of injury. However, no change in number of proliferating CM or cell death (via pHH3 or TUNEL immunohistochemistry respectively) was detected in IR pigs vs sham, or between regions of the left ventricle. Conclusions: Here we report a successful ischemic injury method, at an age previously not reported in swine. Pigs did not continue to decline towards heart failure following an IR injury at 1 month of life, with preservation of EF up to 4-weeks post-injury. This is also without a change in CM cell cycling activity at 2 months of age. This study highlights that even in the presence of a scar, young, large mammals can adapt to cardiac injury to maintain cardiac function. The pathways regulating scar formation and CM cell cycling are being further investigated by RNA-seq studies. If similar mechanisms operate in humans, it may be beneficial to perform CHD surgeries at a younger age when the heart is able to better tolerate injury, to ultimately improve long term outcomes. |
| تدمد: | 1524-4571 0009-7330 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::0d9c820e529958c8e501f3753cbec984Test https://doi.org/10.1161/res.125.suppl_1.131Test |
| رقم الانضمام: | edsair.doi...........0d9c820e529958c8e501f3753cbec984 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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