Name: Comprehensive Echocardiographic Assessment of Right Ventricle Function in a Rat Model of Pulmonary Arterial Hypertension (Video) | JoVE Journal
Uploaded: 2023-01-20T13:45:00.000+00:00
Duration: 7 min 38 s
Description: Learn echocardiographic assessment of right ventricular function in a rat model of pulmonary arterial hypertension. This protocol details imaging techniques to evaluate cardiac morphology and systolic performance using Monocrotaline-induced rats.

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5 minutes

This work was supported by NHLBI K01 HL155241 and AHA CDA849387 awarded to the author P.C.R.

<ol><li>Galie, N., McLaughlin, V. V., Rubin, L. J., Simonneau, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((An+overview+of+the+6th+World+Symposium+on+Pulmonary+Hypertension%5BTitle%5D)+AND+%22European+Respiratory+Journal%22%5BJournal%5D)">An overview of the 6th World Symposium on Pulmonary Hypertension.</a> European Respiratory Journal. 53 (1), 1802148(2019).</li>
<li>Tyagi, S., Batra, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Novel+therapeutic+approaches+of+pulmonary+arterial+hypertension%5BTitle%5D)+AND+%22International+Journal+of+Angiology%22%5BJournal%5D)">Novel therapeutic approaches of pulmonary arterial hypertension.</a> International Journal of Angiology. 28 (2), 112-117 (2019).</li>
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<li>Zolty, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Novel+experimental+therapies+for+treatment+of+pulmonary+arterial+hypertension%5BTitle%5D)+AND+%22Journal+of+Experimental+Pharmacology%22%5BJournal%5D)">Novel experimental therapies for treatment of pulmonary arterial hypertension.</a> Journal of Experimental Pharmacology. 13, 817-857 (2021).</li>
<li>Jasmin, J. F., Lucas, M., Cernacek, P., Dupuis, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effectiveness+of+a+nonselective+ET%28A%2FB%29+and+a+selective+ET%28A%29+antagonist+in+rats+with+monocrotaline-induced+pulmonary+hypertension%5BTitle%5D)+AND+%22Circulation%22%5BJournal%5D)">Effectiveness of a nonselective ET(A/B) and a selective ET(A) antagonist in rats with monocrotaline-induced pulmonary hypertension.</a> Circulation. 103 (2), 314-318 (2001).</li>
<li>Stenmark, K. R., Meyrick, B., Galie, N., Mooi, W. J., McMurtry, I. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Animal+models+of+pulmonary+arterial+hypertension%3A+the+hope+for+etiological+discovery+and+pharmacological+cure%5BTitle%5D)+AND+%22American+Journal+of+Physiology+Lung+Cellular+and+Molecular+Physiology%22%5BJournal%5D)">Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure.</a> American Journal of Physiology Lung Cellular and Molecular Physiology. 297 (6), 1013-1032 (2009).</li>
<li>Muresian, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+clinical+anatomy+of+the+right+ventricle%5BTitle%5D)+AND+%22Clinical+Anatomy%22%5BJournal%5D)">The clinical anatomy of the right ventricle.</a> Clinical Anatomy. 29 (3), 380-398 (2016).</li>
<li>Rudski, L. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Guidelines+for+the+echocardiographic+assessment+of+the+right+heart+in+adults%3A+a+report+from+the+American+Society+of+Echocardiography+endorsed+by+the+European+Association+of+Echocardiography%2C+a+registered+branch+of+the+European+Society+of+Cardiology%2C+and+the+Canadian+Society+of+Echocardiography%5BTitle%5D)+AND+%22Journal+of+the+American+Society+of+Echocardiography%22%5BJournal%5D)">Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography.</a> Journal of the American Society of Echocardiography. 23 (7), 685-713 (2010).</li>
<li>Jones, N., Burns, A. T., Prior, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Echocardiographic+assessment+of+the+right+ventricle-state+of+the+art%5BTitle%5D)+AND+%22Heart+Lung+and+Circulation%22%5BJournal%5D)">Echocardiographic assessment of the right ventricle-state of the art.</a> Heart Lung and Circulation. 28 (9), 1339-1350 (2019).</li>
<li>Spyropoulos, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Echocardiographic+markers+of+pulmonary+hemodynamics+and+right+ventricular+hypertrophy+in+rat+models+of+pulmonary+hypertension%5BTitle%5D)+AND+%22Pulmonary+Circulation%22%5BJournal%5D)">Echocardiographic markers of pulmonary hemodynamics and right ventricular hypertrophy in rat models of pulmonary hypertension.</a> Pulmonary Circulation. 10 (2), 2045894020910976(2020).</li>
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<li>Kimura, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Evaluation+of+right+ventricle+by+speckle+tracking+and+conventional+echocardiography+in+rats+with+right+ventricular+heart+failure%5BTitle%5D)+AND+%22International+Heart+Journal%22%5BJournal%5D)">Evaluation of right ventricle by speckle tracking and conventional echocardiography in rats with right ventricular heart failure.</a> International Heart Journal. 56 (3), 349-353 (2015).</li>
<li>Cheng, H. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Assessment+of+right+ventricular+structure+and+function+in+mouse+model+of+pulmonary+artery+constriction+by+transthoracic+echocardiography%5BTitle%5D)+AND+%22Journal+of+Visualized+Experiments%22%5BJournal%5D)">Assessment of right ventricular structure and function in mouse model of pulmonary artery constriction by transthoracic echocardiography.</a> Journal of Visualized Experiments. 84, e51041(2014).</li>
<li>Mazurek, J. A., Vaidya, A., Mathai, S. C., Roberts, J. D., Forfia, P. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Follow-up+tricuspid+annular+plane+systolic+excursion+predicts+survival+in+pulmonary+arterial+hypertension%5BTitle%5D)+AND+%22Pulmonary+Circulation%22%5BJournal%5D)">Follow-up tricuspid annular plane systolic excursion predicts survival in pulmonary arterial hypertension.</a> Pulmonary Circulation. 7 (2), 361-371 (2017).</li>
<li>Grapsa, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Echocardiographic+and+hemodynamic+predictors+of+survival+in+precapillary+pulmonary+hypertension%3A+seven-year+follow-up%5BTitle%5D)+AND+%22Circulation%3A+Cardiovascular+Imaging%22%5BJournal%5D)">Echocardiographic and hemodynamic predictors of survival in precapillary pulmonary hypertension: seven-year follow-up.</a> Circulation: Cardiovascular Imaging. 8 (6), 002107(2015).</li>
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</ol>

The authors have nothing to disclose.

Echocardiographic evaluation of the RV is a valuable discovery tool for the screening of the effectiveness of novel treatments in animal models of PAH. In-depth characterization of the RV structure and function is necessary as novel targets in treating PAH address RV remodeling4,14. This study describes a detailed protocol that allows for the successful characterization of RV structure and function.
The complex structural geometry and ...

PAH is a progressive disease defined as a mean pulmonary arterial pressure at rest of greater than 20 mmHg1. Pathological changes in PAH include pulmonary artery (PA) remodeling, vasoconstriction, inflammation, and fibroblast activation and proliferation. These pathological changes lead to increased pulmonary vascular resistance and, consequently, right ventricular remodeling, hypertrophy, and failure2. PAH is a complex disease that involves crosstalk between several signaling pathways. The currently approved drugs for treating PAH mostly target vasodilator pathways, including the nitric oxide-cyclic guanosine monophosphate pathway, prostacyclin pathway, and endothelin pathway. Therapeutics targeting these pathways have been used as both monotherapies and in combination therapies3,4. Despite the advances in treatment for PAH in the last decade, findings from the US-based REVEAL registry show a poor 5 year survival rate for newly diagnosed patients5. More recently, emerging therapeutic modalities have focused on disease-modifying agents that can impact the multifactorial pathophysiology of the vascular remodeling occurring in PAH in the hope of disrupting the disease6.
Animal models of PAH are invaluable tools in assessing the efficacy of new drug treatments. The MCT-induced PAH rat model is a widely used animal model characterized by remodeling of the pulmonary arterial vessels, which in turn leads to increased pulmonary vascular resistance and right ventricular hypertrophy and dysfunction7,8. To assess the efficacy of new treatments, researchers normally focus on the terminal assessment of RV pressure without considering the longitudinal evaluation of PA pressure, RV morphology, and RV function. The use of noninvasive and non-terminal imaging techniques is crucial for a comprehensive examination of disease progression in animal models. Transthoracic echocardiography remains the standard approach to evaluating heart morphology and function in animal models due to its low cost and ease of use compared to other imaging modalities, such as magnetic resonance imaging. However, echocardiographic evaluation of the RV can be challenging due to the RV positioning beneath the sternum shadow, its well-developed trabeculation, and its anatomical shape, all of which make it difficult to delineate the endocardial border9,10,11.
This article aims to describe a comprehensive protocol to evaluate RV dimensions, areas and volumes, and systolic and diastolic function in naive and MCT-induced PAH in Sprague Dawley (SD) rats. Additionally, this protocol details a method to assess echocardiographic dimensions in the normal and dilated right atrium.

<table><tbody><tr><td>0.9% sodium cloride injection USP</td><td>Baxter</td><td>2B1324</td><td></td></tr><tr><td>Braided cotton rolls</td><td>4MD Medical Solutions</td><td>RIHD201205</td><td></td></tr><tr><td>Depilating agent</td><td>Wallgreens</td><td>Nair Hair Remover&amp;nbsp;</td><td></td></tr><tr><td>Electrode gel</td><td>Parker Laboratories&amp;nbsp;</td><td>15-60</td><td></td></tr><tr><td>High frequency ultrasound image system and imaging station</td><td>FUJIFILM VisualSonics, Inc.</td><td>Vevo 2100</td><td></td></tr><tr><td>Isoflurane</td><td>MedVet</td><td>RXISO-250</td><td></td></tr><tr><td>Male sprague Dawley rats</td><td>Charles River Laboratories</td><td>CD 001</td><td>CD IGS Rats (Crl:CD(SD))</td></tr><tr><td>Monocrotaline (MCT)</td><td>Sigma-Aldrich</td><td>C2401</td><td></td></tr><tr><td>Rectal temperature probe &amp;nbsp;</td><td>Physitemp&amp;nbsp;</td><td>RET-3</td><td></td></tr><tr><td>Sealed induction chambers</td><td>Scivena Scientific</td><td>RES644&amp;nbsp;</td><td>3 L size</td></tr><tr><td>Solid-state array ultrasound transducer</td><td>FUJIFILM VisualSonics, Inc.</td><td>Vevo MicroScan transducer MS250S</td><td></td></tr><tr><td>Stainless steel digital calipers</td><td>VWR Digital Calipers</td><td>62379-531</td><td></td></tr><tr><td>Ultrasound gel&amp;nbsp;</td><td>Parker Laboratories&amp;nbsp;</td><td>11-08</td><td></td></tr><tr><td>Vevo Lab software</td><td>FUJIFILM VisualSonics, Inc.</td><td></td><td>Verison 5.5.1</td></tr></tbody></table>

comprehensive echocardiographic assessment of right ventricle function in a rat model of pulmonary arterial hypertension

Comprehensive Echocardiographic Assessment of Right Ventricle Function in a Rat Model of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease caused by vasoconstriction and remodeling of the small arteries in the lungs. This remodeling leads to increased pulmonary vascular resistance, worsened right ventricular function, and premature death. Currently approved therapies for PAH largely target pulmonary vasodilator pathways; however, recent emerging therapeutic modalities are focused on other novel pathways involved in the pathogenesis of the disease, including right ventricle (RV) remodeling. Imaging techniques that allow longitudinal assessment of novel therapeutics are very useful for determining the efficacy of new drugs in preclinical studies. Noninvasive trans-thoracic echocardiography remains the standard approach to evaluating heart function and is widely used in rodent models. However, echocardiographic evaluation of the RV can be challenging due to its anatomical position and structure. In addition, standardized guidelines are lacking for echocardiography&#160;in preclinical rodent models, making it difficult to carry out a uniform assessment of RV&#160;function across studies in different laboratories. In preclinical studies, the monocrotaline (MCT) injury model in rats is widely used to evaluate drug efficacy for treating PAH. This protocol describes the echocardiographic evaluation of the RV in na&#239;ve and MCT-induced PAH rats.

In this study, MCT-treated rats were used as a model of PAH. Echocardiographic analysis was performed on Study Day 23 post-MCT administration, and all measurements and calculations represented averages from three consecutive cycles. Echocardiographic parameters obtained from control (vehicle: deionized water) and MCT-treated (60 mg/kg) rats are shown in Table 1.
Representative images of the PLAX view in control and MCT-treated rats are shown in Figure 1A</...

The present protocol describes the echocardiographic characterization of right ventricular morphology and function in a rat model of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease caused by vasoconstriction and remodeling of the small arteries in the lungs. This ...

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This article provides a protocol for the echocardiographic assessment of right ventricular size and pulmonary hypertension in mice.  Applications include phenotype determination and serial assessment in transgenic and toxin-induced mouse models of cardiomyopathy and pulmonary vascular disease.

Echocardiographic Assessment of the Right Heart in Mice

Right ventricle (RV) dysfunction is critical to the pathogenesis of cardiovascular disease, yet limited methodologies are available for its evaluation. Recent advances in ultrasound imaging provide a noninvasive and accurate option for longitudinal RV study. Herein, we detail a step-by-step echocardiographic method using a murine model of RV pressure overload.

Assessment of Right Ventricular Structure and Function in Mouse Model of Pulmonary Artery Constriction by Transthoracic Echocardiography

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Right Ventricular (RV) dysfunction were induced in piglets by progressive obstruction of the pulmonary arteries. Consequences were remarkably similar to those observed in CTEPH patients. This animal model would be a very useful tool for pathophysiology and therapeutic experiments on CTEPH and RV failure.

Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet

Pulmonary arterial hypertension (PAH) is a disease of pulmonary arterioles that leads to their obliteration and the development of right ventricular failure. Rodent models of PAH are critical in understanding the pathophysiology of PAH. Here we demonstrate hemodynamic characterization, with right heart catheterization and echocardiography, in the mouse and rat.

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

This protocol describes a surgical procedure to create a model for flow-induced pulmonary arterial hypertension (PAH) in rats and the procedures to analyze the principle hemodynamic and histological end-points in this model.

Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension

Here, we provide a useful approach for studying the mechanism of right ventricular failure. A more convenient and efficient approach to pulmonary artery constriction is established using surgical instruments made inhouse. In addition, methods to evaluate the quality of this approach by echocardiography and catheterization are provided.

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice

Here, we present a protocol to perform an invasive hemodynamic assessment of the right ventricle and pulmonary artery in mice using an open-chest surgery approach.

Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice

A non-invasive protocol for transthoracic echocardiography assessment of cardiac anatomy and function for adult rats is presented in the current study. The heart valves, all four cardiac chambers and the ascending aorta, aortic arch and descending aorta are studied in detail.

Echocardiographic Assessment of Cardiac Anatomy and Function in Adult Rats

Here, the method of inducing pulmonary arterial hypertension associated with pulmonary fibrosis (PF-PH) rat model by injecting bleomycin into the airway is introduced. We also provide a step-by-step approach to validate this animal model.

Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis

The presentation of detailed methods for the evaluation of right ventricle function will enhance the quality and reliability of pulmonary hypertension research, offering a robust framework for future studies and enhancing reproducibility across different laboratories.

Evaluation of Right Ventricular Function in Experimental Models of Pulmonary Arterial Hypertension

Learn echocardiographic assessment of right ventricular function in a rat model of pulmonary arterial hypertension. This protocol details imaging techniques to evaluate cardiac morphology and systolic performance using Monocrotaline-induced rats.

Comprehensive Echocardiographic Assessment of Right Ventricle Function in a Rat Model of Pulmonary Arterial Hypertension

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