Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA.
Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
Cells. 2020 Jan 16;9(1):229. doi: 10.3390/cells9010229.
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%, < 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, = 0.2511), left ventricular wall thickness ( = 0.9458), or chamber diameter ( = 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 ( = 0.0072), Ki-67 ( = 0.0340), and aurora B kinase ( = 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.
新生鼠和仔猪在心肌梗死（MI）后表现出天然的心脏再生。发现其他具有这种能力的哺乳动物将为新生儿 MI 后心脏再生可能是一种保守表型提供证据，如果在成年人中激活，这可能为治疗人类缺血性心肌病开辟新的选择。在这里，我们假设新生大鼠在 MI 后会经历天然的心脏再生。我们在低温循环骤停下对 1 天大的大鼠进行左前降支冠状动脉结扎或假手术（MI 组 n = 74），建立新生大鼠 MI 模型。手术存活率为 97.3%。手术后 1 天，MI 组大鼠的射血分数（EF）明显低于假手术组（87.1% vs. 53.0%，<0.0001）。手术后 3 周，假手术组和 MI 组大鼠的 EF（分别为 71.1%和 69.2%，= 0.2511）、左心室壁厚度（= 0.9458）或腔径（= 0.7801）均无差异。Masson 三色和苦味酸天狼猩红染色显示 MI 后胶原疤痕很少。在 MI 后梗死周边区域观察到 5-乙炔基-2'-脱氧尿苷（= 0.0072）、Ki-67（= 0.0340）和极光激酶 B（= 0.0430）阳性的心肌细胞数量增加，表明缺血诱导的心肌细胞增殖。总之，我们提出了一种新生大鼠 MI 模型，并证明新生大鼠在 MI 后能够进行内源性心肌生成。
