Abstract 13672: High Frequency Echocardiography and Speckle Tracking Based Strain Analysis Revealed Delayed Functional Recovery After Myocardial Cryoinjury in Adult Zebrafish

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Selina Hein ◽  
Lorenz Lehmann ◽  
Hugo A Katus ◽  
David Hassel

Zebrafish is a widespread used model in cardiovascular research, and recently adult zebrafish, as a more human relevant model compared to larval stages, became particularly valuable to study heart regeneration. While cardiac performance in larval stages can be easily assessed using transillumination microscopy, methods to reliably assess cardiac function in adult zebrafish are largely missing. Here, we developed the first standardized protocol to reliably assess cardiac function in adult zebrafish using high frequency echocardiography and speckle-tracking algorithms. Respecting distinct anatomic characteristics in zebrafish, we defined three examination planes according to standards in human echocardiography. Further, by combining conventional echocardiographic measurements with modern speckle tracking based strain analysis we are able to measure myocardial performance in extremely high spatial and temporal resolution. Thereby we were able to attain high quality B-Mode imaging and PW-Doppler signals allowing distinct detection of changes in chronotropy, inotropy and, for the first time in adult zebrafish, in dromotropy in response to treatment with Atenolol and Isoproterenol. Additionally, we employed zebrafish that underwent cardiac cryoinjury to longitudinally follow functional cardiac regeneration. High-resolution speckle-tracking strain analysis allowed us to demarcate injured myocardial regions and demonstrate that functional healing extends beyond 30-45 days post injury (dpi) as previously implied by conventional methodologies. Specifically, we found delayed restitution of cardiac displacement and re-synchronization of injured and non-injured myocardium beyond 60 dpi until 120 dpi. In summary, our protocol enables highly reproducible and high throughput measurements of cardiac performance in adult zebrafish in a high spatio-temporal resolution. Thereby, our protocol represents a valuable novel tool for functional cardiac assessment and to detect changes in cardiac function in response to gene mutation or myocardial injury and might lead to further insights into cardiac physiology and disease.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Tonya Coulthard ◽  
Jun Wu

Introduction: Ultrasound (US) is a standard for the assessment of cardiovascular function. Pre-clinically, this is due the modality’s translational potential, its high temporal resolution and the absence of infrastructure. Recent advancements in novel high-performance compact MRI has made cardiac MRI a more accessible technique for assessing a variety of pathologies in murine models of CVD while reducing the complexity and costs traditionally associated with superconducting MRI systems. These developments may allow compact MRI to overcome some of the limitations of US meanwhile producing viable solutions for quantification along with new capabilities for cardiovascular biomarker assessment. Hypothesis: This study explores the relative capabilities of novel compact high-performance MRI compared to HFU for phenotypic analysis of mouse models of CVD. Methods: Four normal and one induced myocardial infarct C57BL/6 mice were imaged using both US and MRI. MI mice were prepared by ligation of the left anterior descending artery. In order to assess the ability of each modality to qualitatively and quantitatively characterize cardiac function, CINE loops of long axis and short axis slices were acquired with both systems and analyzed offline. In addition to traditional measures of cardiac function, strain analysis was performed using the HARP method for compact MRI and using speckle tracking for US. Finally, a cardiac MRI method for mapping and measuring infarct extent using gadolinium (Gd) contrast agents is described. Results and Conclusions: Although compact MRI has lower temporal resolution, when compared with US, it still provides many advantages in pre-clinical CVD imaging. In particular, because MRI signal is not attenuated by dense tissue or air, compact MRI can successfully generate artefact-free imaging of pathologies difficult or impossible to image with US, such as clearly visualizing and quantifying endo and epicardial borders. It also provides a whole body image and a “whole heart” image, making pre-clinical CV imaging easier for biologists and helping to reduce inter-operator variability. Finally, high sensitivity to Gd-based contrast agent with compact MRI enable new applications such as infarct quantification.


Author(s):  
S.I. Buryakova, M.V. Medvedev

The article deals with the physiology of the heart and methods to assess fetal cardiac function. The leadingedge technique to assess the myocardial deformation properties by speckle tracking echocardiography in prenatal period is presented.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Saikrishna Ananthapadmanabhan ◽  
Giau Vo ◽  
Tuan Nguyen ◽  
Hany Dimitri ◽  
James Otton

Abstract Background Cardiac magnetic resonance feature tracking (CMR-FT) and speckle tracking echocardiography (STE) are well-established strain imaging modalities. Multilayer strain measurement permits independent assessment of endocardial and epicardial strain. This novel and layer specific approach to evaluating myocardial deformation parameters may provide greater insight into cardiac contractility when compared to whole-layer strain analysis. The aim of this study is to validate CMR-FT as a tool for multilayer strain analysis by providing a direct comparison between multilayer global longitudinal strain (GLS) values between CMR-FT and STE. Methods We studied 100 patients who had an acute myocardial infarction (AMI), who underwent CMR imaging and echocardiogram at baseline and follow-up (48 ± 13 days). Dedicated tissue tracking software was used to analyse single- and multi-layer GLS values for CMR-FT and STE. Results Correlation coefficients for CMR-FT and STE were 0.685, 0.687, and 0.660 for endocardial, epicardial, and whole-layer GLS respectively (all p < 0.001). Bland Altman analysis showed good inter-modality agreement with minimal bias. The absolute limits of agreement in our study were 6.4, 5.9, and 5.5 for endocardial, whole-layer, and epicardial GLS respectively. Absolute biases were 1.79, 0.80, and 0.98 respectively. Intraclass correlation coefficient (ICC) values showed moderate agreement with values of 0.626, 0.632, and 0.671 respectively (all p < 0.001). Conclusion There is good inter-modality agreement between CMR-FT and STE for whole-layer, endocardial, and epicardial GLS, and although values should not be used interchangeably our study demonstrates that CMR-FT is a viable imaging modality for multilayer strain


2019 ◽  
Vol 6 (2) ◽  
pp. 16 ◽  
Author(s):  
Suneeta Narumanchi ◽  
Karri Kalervo ◽  
Sanni Perttunen ◽  
Hong Wang ◽  
Katariina Immonen ◽  
...  

The let-7c family of micro-RNAs (miRNAs) is expressed during embryonic development and plays an important role in cell differentiation. We have investigated the role of let-7c in heart regeneration after injury in adult zebrafish. let-7c antagomir or scramble injections were given at one day after cryoinjury (1 dpi). Tissue samples were collected at 7 dpi, 14 dpi and 28 dpi and cardiac function was assessed before cryoinjury, 1 dpi, 7 dpi, 14 dpi and 28 dpi. Inhibition of let-7c increased the rate of fibrinolysis, increased the number of proliferating cell nuclear antigen (PCNA) positive cardiomyocytes at 7 dpi and increased the expression of the epicardial marker raldh2 at 7 dpi. Additionally, cardiac function measured with echocardiography recovered slightly more rapidly after inhibition of let-7c. These results reveal a beneficial role of let-7c inhibition in adult zebrafish heart regeneration.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Christopher J Traynham ◽  
Ancai Yuan ◽  
Erhe Gao ◽  
Walter Koch

In the next 35 years, the global population of individuals above 60 years of age will double to approximately 2 billion. In the aged population, cardiovascular diseases are known to occur at a higher prevalence ultimately leading to increased mortality. G protein-coupled receptors (GPCRs) have been identified as vital regulators of cardiac function. GPCR kinases (GRKs) are important in cardiac GPCR regulation through desensitization of these receptors. GRK2 is highly expressed in the heart, and has been widely characterized due to its upregulation in heart failure. Studies from our lab have shown that elevated GRK2 levels in ischemia-reperfusion (I/R) injury result in a pro-death phenotype. Interestingly, cardio-protection can be inferred via S-nitrosylation of GRK2 at cysteine 340. Further, we have generated a knock-in GRK2 340S mouse, in which cysteine 340 was mutated to block dynamic GRK2 S-nitrosylation. GRK2 340S mice are more susceptible to I/R injury. Given that GRK2 340S mice are more susceptible to oxidative stress, and there is a nitroso-redox imbalance in senescence, it is possible that these mice are more likely to exhibit decreased cardiac performance as they age. Therefore, we hypothesize that with age GRK2 340S knockin mice will develop an overall worsened cardiac phenotype compared to control wild-type (WT) mice. To test this hypothesis, 340S and WT mice were aged for a year, and cardiac function was evaluated via echocardiography. Aged 340S mice exhibited significantly decreased ejection fraction and fraction shortening relative to aged WT controls. Prior to tissue harvesting, in-vivo hemodynamics was conducted via Millar catheterization. At baseline, aged 340S mice exhibited increased systolic blood pressure compared to aged WT mice. At the conclusion of this protocol, mice were sacrificed and heart weight (HW), body weight (BW), and tibia length (TL) measured to evaluate cardiac hypertrophy. Aged 340S mice exhibited significantly increased HW/BW and HW/TL ratios, indicative of cardiac hypertrophy, relative to aged WT controls. Taken together, these data suggest that with age, loss of the cardio protection inferred by S-nitrosylation of GRK2 at leads to decreased cardiac performance, and an overall worsened cardiac phenotype.


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