Department of Cardiology, University of Bonn, Bonn, Germany.
Institute of Physiology I, Life & Brain Center, University of Bonn, Bonn, Germany.
PLoS One. 2019 Feb 14;14(2):e0208301. doi: 10.1371/journal.pone.0208301. eCollection 2019.
Clinical and experimental data give evidence that transplantation of stem and progenitor cells in myocardial infarction could be beneficial, although the underlying mechanism has remained elusive. Ventricular tachyarrhythmia is the most frequent and potentially lethal complication of myocardial infarction, but the impact of mono nuclear cells on the incidence of ventricular arrhythmia is still not clear.
We aimed to characterize the influence of splenic mononuclear cell populations on ventricular arrhythmia after myocardial infarction.
We assessed electrical vulnerability in vivo in mice with left ventricular cryoinfarction 14 days after injury and intramyocardial injection of specific subpopulations of mononuclear cells (MNCs) (CD11b-positive cells, Sca-1-positive cells, early endothelial progenitor cells (eEPCs)). As positive control group we used embryonic cardiomyocytes (eCMs). Epicardial mapping was performed for analysing conduction velocities in the border zone. Left ventricular function was quantified by echocardiography and left heart catheterization.
In vivo pacing protocols induced ventricular tachycardia (VT) in 30% of non-infarcted mice. In contrast, monomorphic or polymorphic VT could be evoked in 94% of infarcted and vehicle-injected mice (p<0.01). Only transplantation of eCMs prevented post-infarction VT and improved conduction velocities in the border zone in accordance to increased expression of connexin 43. Cryoinfarction resulted in a broad aggravation of left ventricular function. All transplanted cell types augmented left ventricular function to a similar extent.
Transplantation of different MNC populations after myocardial infarction improves left ventricular function similar to effects of eCMs. Prevention of inducible ventricular arrhythmia is only seen after transplantation of eCMs.
临床和实验数据表明，干细胞和祖细胞移植治疗心肌梗死可能有益，尽管其潜在机制仍不清楚。室性心动过速是心肌梗死最常见且潜在致命的并发症，但单核细胞对室性心律失常发生率的影响尚不清楚。
我们旨在研究脾单核细胞群体对心肌梗死后室性心律失常的影响。
我们在左心室冷冻心肌梗死 14 天后，通过体内评估损伤小鼠的电易损性，并对单核细胞（CD11b 阳性细胞、Sca-1 阳性细胞、早期内皮祖细胞（eEPCs））的特定亚群进行心肌内注射。我们使用胚胎心肌细胞（eCMs）作为阳性对照组。进行心外膜标测以分析边缘区的传导速度。通过超声心动图和左心导管术定量左心室功能。
在非梗死小鼠中，体内起搏方案可诱发性室性心动过速（VT），发生率为 30%。相比之下，在梗死和载体注射的小鼠中，94%可诱发性单形或多形 VT（p<0.01）。只有移植 eCMs 才能预防梗死后 VT，并根据连接蛋白 43 的表达增加改善边缘区的传导速度。冷冻心肌梗死导致左心室功能广泛恶化。所有移植的细胞类型均使左心室功能得到相似程度的改善。
心肌梗死后移植不同的单核细胞群体可改善左心室功能，与 eCMs 的作用相似。只有移植 eCMs 后才可以预防可诱导性室性心律失常。
