Advanced echocardiography in adult zebrafish reveals delayed recovery of heart function after myocardial cryoinjury.

Advanced echocardiography in adult zebrafish reveals delayed recovery of heart function after myocardial cryoinjury.
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DOI:
10.1371/journal.pone.0122665
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Hassel D
Hassel D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hein SJ;Lehmann LH;Kossack M;Juergensen L;Fuchs D;Katus HA;Hassel D

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半透明的斑马鱼幼虫代表了一个成熟的模型来分析心脏发育和人类心脏病的遗传学。最近,成年斑马鱼被用于评估心脏再生机制,并受益于最近的基因组编辑技术,包括TALEN和CRISPR,成年斑马鱼正在成为一种有价值的体内模型,用于评估新的疾病基因,并特异性验证引起疾病的突变及其潜在的病理机制。然而,对成年斑马鱼的心脏形态和功能进行敏感和无创评估的方法仍然有限。我们在这里提出了一个标准化的检查方案,通过先进的传统超声心动图和现代斑点跟踪分析来广泛评估成年斑马鱼的心脏性能。这允许准确检测心脏性能的变化,并进一步在高时空分辨率下对区域心肌运动和变形进行高灵敏度评估。结合常规超声心动图测量心肌冷冻损伤后的径向和纵向速度、位移、应变、应变率和心肌壁延迟率,可以无创地确定损伤尺寸,并在心脏再生过程中纵向跟踪功能恢复。我们发现冷冻损伤心脏的功能恢复发生在三个不同的阶段。重要的是,冷冻损伤后的再生过程远远超过了室室切除后的45天,心肌功能的重建可达损伤后180天(dpi)。这里评估的成像模式允许敏感的心脏表型,并有助于进一步建立成年斑马鱼在幼虫发育阶段之后作为有价值的心脏病模型。
Translucent zebrafish larvae represent an established model to analyze genetics of cardiac development and human cardiac disease. More recently adult zebrafish are utilized to evaluate mechanisms of cardiac regeneration and by benefiting from recent genome editing technologies, including TALEN and CRISPR, adult zebrafish are emerging as a valuable in vivo model to evaluate novel disease genes and specifically validate disease causing mutations and their underlying pathomechanisms. However, methods to sensitively and non-invasively assess cardiac morphology and performance in adult zebrafish are still limited. We here present a standardized examination protocol to broadly assess cardiac performance in adult zebrafish by advancing conventional echocardiography with modern speckle-tracking analyses. This allows accurate detection of changes in cardiac performance and further enables highly sensitive assessment of regional myocardial motion and deformation in high spatio-temporal resolution. Combining conventional echocardiography measurements with radial and longitudinal velocity, displacement, strain, strain rate and myocardial wall delay rates after myocardial cryoinjury permitted to non-invasively determine injury dimensions and to longitudinally follow functional recovery during cardiac regeneration. We show that functional recovery of cryoinjured hearts occurs in three distinct phases. Importantly, the regeneration process after cryoinjury extends far beyond the proposed 45 days described for ventricular resection with reconstitution of myocardial performance up to 180 days post-injury (dpi). The imaging modalities evaluated here allow sensitive cardiac phenotyping and contribute to further establish adult zebrafish as valuable cardiac disease model beyond the larval developmental stage.
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