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.

中文翻译：

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心肌梗死后年龄依赖性自然心脏再生的新生鼠兔模型

目标

新生啮齿动物和小猪在心肌梗塞后自然再生受伤的心脏。我们假设新生兔在心肌梗塞后也表现出自然的心脏再生。

方法

新西兰白兔试剂盒在产后第 1 天（n = 94）、产后第 4 天（n = 11）或产后第 7 天（n = 52）接受了假手术或左冠状动脉结扎。术后 1 天移植心脏以确认缺血性损伤，术后 1 周移植心脏以评估心肌细胞增殖，术后 3 周移植心脏以评估左心室射血分数和疤痕大小。数据以平均值±标准差表示。

结果

心肌梗死后第 1 天和第 7 天的缺血性损伤占左心室面积的百分比相似（42.3% ± 5.4% 对 42.3% ± 4.7%，P = . 9984）。超声心动图证实产后第 1 天心肌梗死后 1 天的射血分数严重降低（产后第 1 天假手术为 33.7% ± 5.3% vs 65.2% ± 5.5%，P = . 0001），但产后第 1 天心肌梗死后 3 周无差异梗塞（56.0% ± 4.0% 对比 58.0% ± 3.3% 产后第 1 天假手术，P = . 2198）。产后第 4 天心肌梗死后射血分数未能恢复（49.2% ± 1.8% vs 产后第 4 天假手术为 58.5% ± 5.8%，P = .0109) 和产后第 7 天心肌梗塞（39.0% ± 7.8% vs 产后第 7 天假手术为 60.2% ± 5.0%，P < . 0001）。梗死后 3 周，纤维化疤痕分别占产后第 1 天、产后第 4 天和产后第 7 天组左心室面积的 5.3% ± 1.9%、14.3% ± 4.9% 和 25.4% ± 13.3%。梗塞周围心肌细胞表达 Ki67（15.9% ± 1.8% vs 10.2% ± 0.8%，P = . 0039）和极光 B 激酶（4.0% ± 0.9% vs 1.5% ± 0.6%，P = . 0088）的比例增加与假手术相比，产后第 1 天心肌梗死后，但在产后第 7 天心肌梗死后未观察到增加。

结论

新生兔兔心肌梗死模型表明，新生兔具有年龄依赖性的自然心脏再生能力。