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A neonatal leporine model of age-dependent natural heart regeneration after myocardial infarction.
Wang, Hanjay; Hironaka, Camille E; Mullis, Danielle M; Lucian, Haley J; Shin, Hye Sook; Tran, Nicholas A; Thakore, Akshara D; Anilkumar, Shreya; Wu, Matthew A; Paulsen, Michael J; Zhu, Yuanjia; Baker, Sam W; Woo, Y Joseph.
Afiliação
  • Wang H; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif; Stanford Cardiovascular Institute, Stanford University, Stanford, Calif.
  • Hironaka CE; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif.
  • Mullis DM; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif.
  • Lucian HJ; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif.
  • Shin HS; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif.
  • Tran NA; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif.
  • Thakore AD; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif.
  • Anilkumar S; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif.
  • Wu MA; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif.
  • Paulsen MJ; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif.
  • Zhu Y; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif; Department of Bioengineering, Stanford University, Stanford, Calif.
  • Baker SW; Department of Comparative Medicine, Stanford University, Stanford, Calif.
  • Woo YJ; Department of Cardiothoracic Surgery, Stanford University, Stanford, Calif; Stanford Cardiovascular Institute, Stanford University, Stanford, Calif; Department of Bioengineering, Stanford University, Stanford, Calif. Electronic address: joswoo@stanford.edu.
J Thorac Cardiovasc Surg ; 164(6): e389-e405, 2022 12.
Article em En | MEDLINE | ID: mdl-34649718
ABSTRACT

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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Função Ventricular Esquerda / Infarto do Miocárdio Limite: Animals Idioma: En Revista: J Thorac Cardiovasc Surg Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Função Ventricular Esquerda / Infarto do Miocárdio Limite: Animals Idioma: En Revista: J Thorac Cardiovasc Surg Ano de publicação: 2022 Tipo de documento: Article