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Open AccessArticle

Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model

Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA
Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 229;
Received: 23 September 2019 / Revised: 6 January 2020 / Accepted: 13 January 2020 / Published: 16 January 2020
Newborn mice and piglets exhibit natural heart regeneration after myocardial infarction (MI). Discovering other mammals with this ability would provide evidence that neonatal cardiac regeneration after MI may be a conserved phenotype, which if activated in adults could open new options for treating ischemic cardiomyopathy in humans. Here, we hypothesized that newborn rats undergo natural heart regeneration after MI. Using a neonatal rat MI model, we performed left anterior descending coronary artery ligation or sham surgery in one-day-old rats under hypothermic circulatory arrest (n = 74). Operative survival was 97.3%. At 1 day post-surgery, rats in the MI group exhibited significantly reduced ejection fraction (EF) compared to shams (87.1% vs. 53.0%, p < 0.0001). At 3 weeks post-surgery, rats in the sham and MI groups demonstrated no difference in EF (71.1% vs. 69.2%, respectively, p = 0.2511), left ventricular wall thickness (p = 0.9458), or chamber diameter (p = 0.7801). Masson’s trichome and picrosirius red staining revealed minimal collagen scar after MI. Increased numbers of cardiomyocytes positive for 5-ethynyl-2′-deoxyuridine (p = 0.0072), Ki-67 (p = 0.0340), and aurora B kinase (p = 0.0430) were observed within the peri-infarct region after MI, indicating ischemia-induced cardiomyocyte proliferation. Overall, we present a neonatal rat MI model and demonstrate that newborn rats are capable of endogenous neocardiomyogenesis after MI. View Full-Text
Keywords: regeneration; heart; neonate; myocardial infarction regeneration; heart; neonate; myocardial infarction
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Wang, H.; Paulsen, M.J.; Hironaka, C.E.; Shin, H.S.; Farry, J.M.; Thakore, A.D.; Jung, J.; Lucian, H.J.; Eskandari, A.; Anilkumar, S.; Wu, M.A.; Cabatu, M.C.; Steele, A.N.; Stapleton, L.M.; Zhu, Y.; Woo, Y.J. Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model. Cells 2020, 9, 229.

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