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

Podsumowanie

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

Streszczenie

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 in preclinical rodent models, making it difficult to carry out a uniform assessment of RV 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 naïve and MCT-induced PAH rats.

Wprowadzenie

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 monophosph....

Protokół

All experiments in this protocol were performed following the animal care guidelines of the University of Illinois at Chicago, Chicago Institutional Animal Care and Use Committee. Male Sprague Dawley (SD) rats weighed between 0.200-0.240 kg at the time of MCT injection; however, the protocol described in this article can be used with a wider body weight range. The animals were obtained from a commercial source (see Table of Materials).

1. Study design

1. Animals
   1. Obtain male SD rats and allow them to acclimate for 4-7 days. Group-house the rats by the experimental group in clean cages an....

Wyniki

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

Dyskusje

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 remodeling^4,14. This study describes a detailed protocol that allows for the successful characterization of RV structure and function.

The complex structural geometry and .......

Materiały

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