TY - JOUR
T1 - A neonatal leporine model of age-dependent natural heart regeneration after myocardial infarction
AU - Wang, Hanjay
AU - Hironaka, Camille E.
AU - Mullis, Danielle M.
AU - Lucian, Haley J.
AU - Shin, Hye Sook
AU - Tran, Nicholas A.
AU - Thakore, Akshara D.
AU - Anilkumar, Shreya
AU - Wu, Matthew A.
AU - Paulsen, Michael J.
AU - Zhu, Yuanjia
AU - Baker, Sam W.
AU - Woo, Y. Joseph
N1 - Publisher Copyright:
© 2021
PY - 2022/12
Y1 - 2022/12
N2 - Objectives: Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction. Methods: New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n = 94), postnatal day 4 (n = 11), or postnatal day 7 (n = 52). Hearts were explanted 1 day postsurgery to confirm ischemic injury, at 1 week postsurgery to assess cardiomyocyte proliferation, and at 3 weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean ± standard deviation. Results: Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3% ± 5.4% vs 42.3% ± 4.7%, P =. 9984). Echocardiography confirmed severely reduced ejection fraction at 1 day after postnatal day 1 myocardial infarction (33.7% ± 5.3% vs 65.2% ± 5.5% for postnatal day 1 sham, P =. 0001), but no difference at 3 weeks after postnatal day 1 myocardial infarction (56.0% ± 4.0% vs 58.0% ± 3.3% for postnatal day 1 sham, P =. 2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2% ± 1.8% vs 58.5% ± 5.8% for postnatal day 4 sham, P =. 0109) and postnatal day 7 myocardial infarction (39.0% ± 7.8% vs 60.2% ± 5.0% for postnatal day 7 sham, P <. 0001). At 3 weeks after infarction, fibrotic scar represented 5.3% ± 1.9%, 14.3% ± 4.9%, and 25.4% ± 13.3% of the left ventricle area in the postnatal day 1, postnatal day 4, and postnatal day 7 groups, respectively. An increased proportion of peri-infarct cardiomyocytes expressed Ki67 (15.9% ± 1.8% vs 10.2% ± 0.8%, P =. 0039) and aurora B kinase (4.0% ± 0.9% vs 1.5% ± 0.6%, P =. 0088) after postnatal day 1 myocardial infarction compared with sham, but no increase was observed after postnatal day 7 myocardial infarction. Conclusions: A neonatal leporine myocardial infarction model reveals that newborn rabbits are capable of age-dependent natural heart regeneration.
AB - Objectives: Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction. Methods: New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n = 94), postnatal day 4 (n = 11), or postnatal day 7 (n = 52). Hearts were explanted 1 day postsurgery to confirm ischemic injury, at 1 week postsurgery to assess cardiomyocyte proliferation, and at 3 weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean ± standard deviation. Results: Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3% ± 5.4% vs 42.3% ± 4.7%, P =. 9984). Echocardiography confirmed severely reduced ejection fraction at 1 day after postnatal day 1 myocardial infarction (33.7% ± 5.3% vs 65.2% ± 5.5% for postnatal day 1 sham, P =. 0001), but no difference at 3 weeks after postnatal day 1 myocardial infarction (56.0% ± 4.0% vs 58.0% ± 3.3% for postnatal day 1 sham, P =. 2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2% ± 1.8% vs 58.5% ± 5.8% for postnatal day 4 sham, P =. 0109) and postnatal day 7 myocardial infarction (39.0% ± 7.8% vs 60.2% ± 5.0% for postnatal day 7 sham, P <. 0001). At 3 weeks after infarction, fibrotic scar represented 5.3% ± 1.9%, 14.3% ± 4.9%, and 25.4% ± 13.3% of the left ventricle area in the postnatal day 1, postnatal day 4, and postnatal day 7 groups, respectively. An increased proportion of peri-infarct cardiomyocytes expressed Ki67 (15.9% ± 1.8% vs 10.2% ± 0.8%, P =. 0039) and aurora B kinase (4.0% ± 0.9% vs 1.5% ± 0.6%, P =. 0088) after postnatal day 1 myocardial infarction compared with sham, but no increase was observed after postnatal day 7 myocardial infarction. Conclusions: A neonatal leporine myocardial infarction model reveals that newborn rabbits are capable of age-dependent natural heart regeneration.
KW - heart regeneration
KW - myocardial infarction
KW - neonate
KW - rabbit
UR - http://www.scopus.com/inward/record.url?scp=85114234628&partnerID=8YFLogxK
U2 - 10.1016/j.jtcvs.2021.08.013
DO - 10.1016/j.jtcvs.2021.08.013
M3 - Article
AN - SCOPUS:85114234628
SN - 0022-5223
VL - 164
SP - e389-e405
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 6
ER -