153 Pressure Overload Greatly Promotes Neonatal Right Ventricular Cardiomyocyte Proliferation-A New Model for the Study of Heart Regeneration

ABSTRACT A 63-year-old woman was admitted with severe respiratory distress requiring mechanical ventilation and shock requiring vasopressor support. She was found to have COVID-19 pneumonia. Focused cardiac ultrasound performed for evaluation of shock was significant for right ventricular dilation and dysfunction with signs of right ventricular pressure overload. Given worsening shock and hypoxemia systemic thrombolysis was administered for presumed massive pulmonary embolism with remarkable improvement of hemodynamics and respiratory failure. In next 24 h patient’s neurologic status deteriorated to the point of unresponsiveness. Emergent computed tomography showed multiple ischemic infarcts concerning for embolic etiology. Focused cardiac ultrasound with agitated saline showed large right to left shunt due to a patent foramen ovale. This was confirmed by transesophageal echocardiogram, 5 months later. This case highlights strengths of focused cardiac ultrasound in critical care setting and in patients with COVID-19 when access to other imaging modalities can be limited.

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Regional shape, global function and mechanics in right ventricular volume and pressure overload conditions: a three-dimensional echocardiography study

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-020-02117-8 ◽

2021 ◽

Author(s):

Jurate Bidviene ◽

Denisa Muraru ◽

Francesco Maffessanti ◽

Egle Ereminiene ◽

Attila Kovács ◽

...

Keyword(s):

Right Ventricular ◽

Interventricular Septum ◽

Three Dimensional ◽

Pressure Overload ◽

Volume Overload ◽

Ventricular Volume ◽

Longitudinal Contraction ◽

Convex Shape ◽

Dimensional Echocardiography ◽

Three Dimensional Echocardiography

AbstractOur aim was to assess the regional right ventricular (RV) shape changes in pressure and volume overload conditions and their relations with RV function and mechanics. The end-diastolic and end-systolic RV endocardial surfaces were analyzed with three-dimensional echocardiography (3DE) in 33 patients with RV volume overload (rToF), 31 patients with RV pressure overload (PH), and 60 controls. The mean curvature of the RV inflow (RVIT) and outflow (RVOT) tracts, RV apex and body (both divided into free wall (FW) and septum) were measured. Zero curvature defined a flat surface, whereas positive or negative curvature indicated convexity or concavity, respectively. The longitudinal and radial RV wall motions were also obtained. rToF and PH patients had flatter FW (body and apex) and RVIT, more convex interventricular septum (body and apex) and RVOT than controls. rToF demonstrated a less bulging interventricular septum at end-systole than PH patients, resulting in a more convex shape of the RVFW (r = − 0.701, p < 0.0001), and worse RV longitudinal contraction (r = − 0.397, p = 0.02). PH patients showed flatter RVFW apex at end-systole compared to rToF (p < 0.01). In both groups, a flatter RVFW apex was associated with worse radial RV contraction (r = 0.362 in rToF, r = 0.482 in PH at end-diastole, and r = 0.555 in rToF, r = 0.379 in PH at end-systole, respectively). In PH group, the impairment of radial contraction was also related to flatter RVIT (r = 0.407) and more convex RVOT (r = − 0.525) at end-systole (p < 0.05). In conclusion, different loading conditions are associated to specific RV curvature changes, that are related to longitudinal and radial RV dysfunction.

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Delineating the molecular and histological events that govern right ventricular recovery using a novel mouse model of pulmonary artery de-banding

Cardiovascular Research ◽

10.1093/cvr/cvz310 ◽

2019 ◽

Vol 116 (10) ◽

pp. 1700-1709 ◽

Cited By ~ 2

Author(s):

Mario Boehm ◽

Xuefei Tian ◽

Yuqiang Mao ◽

Kenzo Ichimura ◽

Melanie J Dufva ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Mouse Model ◽

Pulmonary Artery ◽

Right Ventricular ◽

Exercise Capacity ◽

Pressure Overload ◽

Left Ventricular ◽

Sequence Of Events ◽

Reverse Remodelling ◽

Rv Function

Abstract Aims The temporal sequence of events underlying functional right ventricular (RV) recovery after improvement of pulmonary hypertension-associated pressure overload is unknown. We sought to establish a novel mouse model of gradual RV recovery from pressure overload and use it to delineate RV reverse-remodelling events. Methods and results Surgical pulmonary artery banding (PAB) around a 26-G needle induced RV dysfunction with increased RV pressures, reduced exercise capacity and caused liver congestion, hypertrophic, fibrotic, and vascular myocardial remodelling within 5 weeks of chronic RV pressure overload in mice. Gradual reduction of the afterload burden through PA band absorption (de-PAB)—after RV dysfunction and structural remodelling were established—initiated recovery of RV function (cardiac output and exercise capacity) along with rapid normalization in RV hypertrophy (RV/left ventricular + S and cardiomyocyte area) and RV pressures (right ventricular systolic pressure). RV fibrotic (collagen, elastic fibres, and vimentin+ fibroblasts) and vascular (capillary density) remodelling were equally reversible; however, reversal occurred at a later timepoint after de-PAB, when RV function was already completely restored. Microarray gene expression (ClariomS, Thermo Fisher Scientific, Waltham, MA, USA) along with gene ontology analyses in RV tissues revealed growth factors, immune modulators, and apoptosis mediators as major cellular components underlying functional RV recovery. Conclusion We established a novel gradual de-PAB mouse model and used it to demonstrate that established pulmonary hypertension-associated RV dysfunction is fully reversible. Mechanistically, we link functional RV improvement to hypertrophic normalization that precedes fibrotic and vascular reverse-remodelling events.

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The impact of glucocorticoids on Neuregulin-1/ERBB2 signaling in cardiomyocyte proliferation and heart regeneration

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2019.11.070 ◽

2020 ◽

Vol 140 ◽

pp. 30

Author(s):

Nicola Pianca ◽

Francesca Pontis ◽

Alla Aharonov ◽

Chiara Bongiovanni ◽

Martina Mazzeschi ◽

...

Keyword(s):

Heart Regeneration ◽

Cardiomyocyte Proliferation ◽

Neuregulin 1 ◽

The Impact ◽

Erbb2 Signaling

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A Systematic Exposition of Methods used for Quantification of Heart Regeneration after Apex Resection in Zebrafish

Cells ◽

10.3390/cells9030548 ◽

2020 ◽

Vol 9 (3) ◽

pp. 548 ◽

Cited By ~ 1

Author(s):

Helene Juul Belling ◽

Wolfgang Hofmeister ◽

Ditte Caroline Andersen

Keyword(s):

Human Heart ◽

Quantitative Methods ◽

Heart Function ◽

Heart Regeneration ◽

Cardiomyocyte Proliferation ◽

Ability To Regenerate ◽

Specific Proteins ◽

Heart Injury ◽

Whole Heart ◽

Study Designs

Myocardial infarction (MI) is a worldwide condition that affects millions of people. This is mainly caused by the adult human heart lacking the ability to regenerate upon injury, whereas zebrafish have the capacity through cardiomyocyte proliferation to fully regenerate the heart following injury such as apex resection (AR). But a systematic overview of the methods used to evidence heart regrowth and regeneration in the zebrafish is lacking. Herein, we conducted a systematical search in Embase and Pubmed for studies on heart regeneration in the zebrafish following injury and identified 47 AR studies meeting the inclusion criteria. Overall, three different methods were used to assess heart regeneration in zebrafish AR hearts. 45 out of 47 studies performed qualitative (37) and quantitative (8) histology, whereas immunohistochemistry for various cell cycle markers combined with cardiomyocyte specific proteins was used in 34 out of 47 studies to determine cardiomyocyte proliferation qualitatively (6 studies) or quantitatively (28 studies). For both methods, analysis was based on selected heart sections and not the whole heart, which may bias interpretations. Likewise, interstudy comparison of reported cardiomyocyte proliferation indexes seems complicated by distinct study designs and reporting manners. Finally, six studies performed functional analysis to determine heart function, a hallmark of human heart injury after MI. In conclusion, our data implies that future studies should consider more quantitative methods eventually taking the 3D of the zebrafish heart into consideration when evidencing myocardial regrowth after AR. Furthermore, standardized guidelines for reporting cardiomyocyte proliferation and sham surgery details may be considered to enable inter study comparisons and robustly determine the effect of given genes on the process of heart regeneration.

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