Echocardiographic Assessment of the Right Heart in Mice

Brittain, Evan L.; Penner, Niki; West, James; Hemnes, Anna R.

doi:10.3791/50912

Cited by 18 publications

(19 citation statements)

References 20 publications

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“…Transthoracic Doppler echocardiography is a noninvasive diagnostic tool for patients with suspected PAH, providing information not only about diagnosis but also about the causes or consequences of PAH . This method has been validated for estimating PAP in PAH patients and in rat and mouse models and is becoming increasingly more relevant in murine models of heart diseases . Using this echocardiography modality, and in accordance with the pulmonary vessel remodeling, we found a reduced PAAT:ET ratio in the pulmonary arteries of 3‐month‐old female PSGL‐1 −/− mice, suggesting that PSGL‐1 −/− mice are susceptible to PH at young age.…”

Section: Discussionmentioning

confidence: 54%

Spontaneous Pulmonary Hypertension Associated With Systemic Sclerosis in P‐Selectin Glycoprotein Ligand 1–Deficient Mice

Rafael

Fuente-Fernández

Morales‐Cano

et al. 2020

Arthritis & Rheumatology

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Objective Pulmonary arterial hypertension (PAH), one of the major complications of systemic sclerosis (SSc), is a rare disease with unknown etiopathogenesis and noncurative treatments. As mice deficient in P‐selectin glycoprotein ligand 1 (PSGL‐1) develop a spontaneous SSc‐like syndrome, we undertook this study to analyze whether they develop PAH and to examine the molecular mechanisms involved. Methods Doppler echocardiography was used to estimate pulmonary pressure, immunohistochemistry was used to assess vascular remodeling, and myography of dissected pulmonary artery rings was used to analyze vascular reactivity. Angiotensin II (Ang II) levels were quantified by enzyme‐linked immunosorbent assay, and Western blotting was used to measure Ang II type 1 receptor (AT1R), AT2R, endothelial cell nitric oxide synthase (eNOS), and phosphorylated eNOS expression in lung lysates. Flow cytometry allowed us to determine cytokine production by immune cells and NO production by endothelial cells. In all cases, there were 4–8 mice per experimental group. Results PSGL‐1−/− mice showed lung vessel wall remodeling and a reduced mean ± SD expression of pulmonary AT2R (expression ratio [relative to β‐actin] in female mice age >18 months: wild‐type mice 0.799 ± 0.508 versus knockout mice 0.346 ± 0.229). With aging, female PSGL‐1−/− mice had impaired up‐regulation of estrogen receptor α (ERα) and developed lung vascular endothelial dysfunction coinciding with an increase in mean ± SEM pulmonary Ang II levels (wild‐type 48.70 ± 5.13 pg/gm lung tissue versus knockout 78.02 ± 28.09 pg/gm lung tissue) and a decrease in eNOS phosphorylation, leading to reduced endothelial NO production. These events led to a reduction in the pulmonary artery acceleration time:ejection time ratio in 33% of aged female PSGL‐1−/− mice, indicating pulmonary hypertension. Importantly, we found expanded populations of interferon‐γ–producing PSGL‐1−/− T cells and B cells and a reduced presence of regulatory T cells. Conclusion The absence of PSGL‐1 induces a reduction in Treg cells, NO production, and ERα expression and causes an increase in Ang II in the lungs of female mice, favoring the development of PAH.

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Section: Discussionmentioning

confidence: 54%

Spontaneous Pulmonary Hypertension Associated With Systemic Sclerosis in P‐Selectin Glycoprotein Ligand 1–Deficient Mice

Rafael

Fuente-Fernández

Morales‐Cano

et al. 2020

Arthritis & Rheumatology

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“…Open-chest PV loops allow a quantification of RV function; for example, in the rat MCT model, losartan significantly reduced RV afterload, restored ventricular-arterial coupling and improved RV diastolic function 16 . Noninvasive parameters derived from echocardiography have been used to estimate stroke volume, cardiac output and an estimate of PA pressures 19,20 . In total, these different techniques allow an assessment of the hemodynamic severity of pulmonary vascular disease and the RV response.…”

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confidence: 99%

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

Rajagopal

2016

JoVE

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Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, with significant morbidity and mortality. Rodent models of PAH, in the mouse and the rat, are important for understanding the pathophysiology underlying this rare disease. Notably, different models of PAH may be associated with different degrees of pulmonary hypertension, RV hypertrophy and RV failure. Therefore, a complete hemodynamic characterization of mice and rats with PAH is critical in determining the effects of drugs or genetic modifications on the disease. Here we demonstrate standard procedures for assessment of right ventricular function and hemodynamics in both rat and mouse PAH models. Echocardiography is useful in determining RV function in rats, although obtaining standard views of the right ventricle is challenging in the awake mouse. Access for right heart catheterization is obtained by the internal jugular vein in closed-chest mice and rats. Pressures can be measured using polyethylene tubing with a fluid pressure transducer or a miniature micromanometer pressure catheter. Pressure-volume loop analysis can be performed in the open chest. After obtaining hemodynamics, the rodent is euthanized. The heart can be dissected to separate the RV free wall from the left ventricle (LV) and septum, allowing an assessment of RV hypertrophy using the Fulton index (RV/(LV+S)). Then samples can be harvested from the heart, lungs and other tissues as needed.

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“…In animal models, validation of echocardiography-derived parameters is possible via direct comparison with invasive measurements and morphological analysis. The feasibility of assessing RV function using echocardiography has been demonstrated in mice 12,13 and rats. 14,15 In mice, Doppler imaging has been used to assess RV function.…”

mentioning

confidence: 99%

Pressure Overload Creates Right Ventricular Diastolic Dysfunction in a Mouse Model: Assessment by Echocardiography

Egemnazarov

Schmidt

Crnković

et al. 2015

Journal of the American Society of Echocardiography

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Echocardiographic Assessment of the Right Heart in Mice

Cited by 18 publications

References 20 publications

Spontaneous Pulmonary Hypertension Associated With Systemic Sclerosis in P‐Selectin Glycoprotein Ligand 1–Deficient Mice

Spontaneous Pulmonary Hypertension Associated With Systemic Sclerosis in P‐Selectin Glycoprotein Ligand 1–Deficient Mice

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

Pressure Overload Creates Right Ventricular Diastolic Dysfunction in a Mouse Model: Assessment by Echocardiography

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