Why should I choose the AAS model over other HF models?

The AAS model offers distinct advantages due to its physiological relevance, precisely mimicking chronic pressure overload seen in clinical hypertension and aortic stenosis. Unlike acute models, it allows for the study of gradual cardiac remodeling, providing a more translatable representation of human HF progression. Its high reproducibility and low mortality rate also ensure reliable and consistent data.

What key endpoints and parameters can be measured in the AAS model?

We provide comprehensive evaluation, including functional parameters like ejection fraction and fractional shortening via echocardiography, and detailed pressure-volume loop analysis for contractility. Molecular markers such as gene and protein expression, histological assessments for hypertrophy (HW/BW, H&E) and fibrosis (Masson's, Picrosirius), and biochemical indicators like cardiac troponin levels are routinely measured.

Can the severity of HF be controlled in the AAS model?

Absolutely. The degree of pressure overload can be precisely controlled by adjusting the size of the ligature used for aortic constriction, for example, using different gauge needles (e.g., 22G or 24G). This allows for the induction of varying severities of hypertrophy and HF, enabling researchers to explore dose-dependent effects of therapies or different disease stages.

Is the AAS model suitable for studying both HFpEF and HFrEF?

Yes, the AAS model is versatile enough to study both HFpEF and HFrEF, depending on the timing of assessment and the specific parameters evaluated. Early phases often present with diastolic dysfunction (HFpEF characteristics), while prolonged pressure overload can lead to systolic dysfunction (HFrEF).

Does Creative Biolabs offer custom study designs for specific research needs?

Yes, absolutely. We understand that each research project is unique. Our scientific team works closely with clients to develop highly customized study protocols. This includes tailoring the model's parameters, selection of specific endpoints, duration of the study, and integration of specialized assays to precisely address your research objectives and maximize data utility.

Abdominal Aortic Stenosis induced Left Heart Failure Modeling & Pharmacodynamics Service

At Creative Biolabs, our extensive expertise allows us to provide a diverse range of well-established HF models, meticulously designed to evaluate the efficacy of novel compounds and advance your research.

Introduction

Heart failure (HF) represents a complex and progressive syndrome where the heart struggles to pump sufficient blood for the body's needs. This debilitating condition significantly impacts patients' quality of life and imposes a substantial burden on global healthcare systems. Effective therapeutic development hinges on the availability of robust, clinically relevant preclinical models.

Abdominal Aortic Stenosis-Induced Left HF Model

The abdominal aortic stenosis (AAS) model is a highly regarded and versatile preclinical platform for investigating chronic pressure overload-induced left ventricular hypertrophy and subsequent HF. It offers a physiologically relevant approach to understanding the complex cascade of cardiac remodeling, closely mirroring human conditions such as aortic stenosis and systemic hypertension.

Model Construction Steps

The construction strategy for the AAS model centers on creating a sustained increase in left ventricular afterload through precise surgical constriction of the abdominal aorta. Our method ensures reproducibility and minimizes complications:

01Incision and Exposure

A small abdominal incision, typically around 1.5 cm, is made to gain access to the abdominal cavity.

02Aorta Localization

Our experienced surgeons meticulously locate the abdominal aorta. The splenic vein often serves as a key anatomical landmark for quick and accurate identification of the target vessel.

03Ligation

The aorta is then carefully ligated, typically with a non-absorbable material, at a strategic point approximately 0.5 cm above the renal arteries.

04Diameter Reduction

This ligation is performed to consistently reduce the aortic diameter to a specific extent, commonly around 0.7 mm, which ensures a precise and reproducible level of pressure overload on the left ventricle.

05Minimizing Manipulation

A key refinement in our technique involves minimizing manipulation of the surrounding gastrointestinal tract. This approach significantly reduces the risk of post-surgical complications such as intestinal obstruction, contributing to improved animal welfare and more consistent study outcomes.

Animals:

Rat, Rabbit, Dog, NHPs

Strengths and Limitations

Strengths:

High Physiological Relevance: Faithfully replicates the gradual onset and progression of cardiac hypertrophy and HF seen in human conditions like hypertension and aortic stenosis.
Controllable Severity: Allows precise titration of pressure overload (e.g., using 22 G or 24 G needles) and monitoring of disease progression over defined durations (e.g., 4 weeks for hypertrophy, up to 12 weeks for HF).
Excellent Reproducibility: Features a low surgical mortality rate and a high success rate for consistent left ventricular hypertrophy induction, leading to reliable data.
Cost-Effectiveness: The relatively simple and refined surgical procedure contributes to its overall economic efficiency compared to more complex models.
Systemic Relevance: Can lead to multi-organ dysfunction, similar to human congestive HF, making it valuable for systemic drug discovery.

Limitations:

Surgical Skill Dependence: Optimal outcomes require highly experienced surgical teams to ensure precise constriction and minimize complications.
Progressive Nature: While a strength for chronic studies, the gradual progression might require longer study durations compared to acute injury models.
Species Specificity: Primarily validated in rodents (rats and mice), findings may require careful consideration when extrapolating to larger animal models or humans without further validation.

Evaluation Platform

Creative Biolabs offers a robust, multidisciplinary evaluation platform to characterize the AAS model and assess therapeutic interventions, providing a holistic view of cardiac health and disease progression.

Imaging Instruments and Tests: High-resolution echocardiography evaluates cardiac structure and function (e.g., ejection fraction, chamber dimensions). Invasive hemodynamics (pressure-volume loop analysis) measures contractility and relaxation, complemented by ECG for electrical activity.
Biochemical & Molecular Analysis: We conduct ELISA for circulating cardiac injury biomarkers (e.g., plasma troponin), and perform Western blotting/qPCR to profile gene/protein expression linked to hypertrophy, fibrosis, and inflammation.
Histopathological & Cellular Analysis: Comprehensive tissue processing involves H&E for hypertrophy, Masson's/Picrosirius Red for fibrosis quantification, and immunohistochemistry for remodeling markers. Heart weight-to-body weight ratio (HW/BW) is also assessed.
Behavioral Tests: Though less common for direct cardiac function, these can evaluate overall animal health and activity changes associated with severe HF.

Applications

Disease Simulation: Simulating systemic hypertension, aortic valve stenosis, and the progression from cardiac hypertrophy to chronic HF (HFpEF/HFrEF).
Pharmacological Evaluation: Rigorous evaluation of novel compounds, including anti-fibrotics, anti-inflammatories, metabolic modulators, and agents improving cardiac contractility or relaxation.
Advanced Therapies Assessment: Assessing cellular and gene therapies for their potential in cardiac regeneration and functional restoration.
Biomarker Discovery: Identifying and validating biomarkers for early diagnosis, prognosis, and therapeutic response.
Mechanistic Studies: Unraveling the intricate mechanisms underpinning cardiac maladaptive remodeling.

Related Heart Failure Models

AMI induced Left HF Model

PA Constriction induced Right HF Model

Ascending Aortic Arch Constriction induced Post-Pressure Overload Heart Failure Model

DOCA & Salt induced Left HF Model

Salt induced Left HF Model

Adriamycin induced Left HF Model

Isoproterenol induced Chronic Heart Failure Model

AngII induced Chronic Heart Failure Model

ACF induced Anterior Pressure Overload Heart Failure Model

HFD induced Heart Failure Model

HFHC Diet induced Heart Failure Model

5/6 Nephrectomy induced Heart Failure Model

Pulmonary Hypertension induced Right Heart Failure Model

Renal Artery Constriction induced Hypertensive Heart Failure Model

Doxorubicin induced Cardiomyopathy Model

Our Advantages

Decades of Expertise: Years of specialized experience in preclinical cardiovascular models, ensuring unparalleled scientific insight.
Refined Surgical Precision: Our skilled surgical team utilizes advanced techniques, including anatomical markers and minimal invasive approaches, for highly consistent and reproducible model generation with low mortality.
Comprehensive Phenotyping Capabilities: We offer a full spectrum of state-of-the-art functional, molecular, and histological assessments for robust data collection.
Customized Study Design: Flexible and tailored experimental protocols to meet your unique research objectives and deliver actionable insights.
Commitment to Quality: Adherence to the highest standards of animal welfare and scientific rigor, guaranteeing reliable and impactful results.

Work with Us

Inquiry Stage

Summarize the project requirements and fill in the information collection form.
Sign a CDA from both parties to further communicate information, such as targets.
Select an animal model, discuss experimental design, and determine assay parameters.
Project costing and project schedule forecasting.

Project Start

We provide a detailed project plan, including the required sample quantities, methods, and protocols.
Both parties confirm the project details and start the project.
Confirm the timeline of the project.

Project Progress

We provide periodic results and information on the animal's condition.
We will work together to make project adjustments as necessary.

Project Completion

We provide a comprehensive project report promptly.
We arrange transportation for the produced samples.
We provide a discussion of the project results and help to arrange the next steps.

After-Sales Support

Data storage and archiving.

Contact Us

Creative Biolabs is dedicated to providing robust and reliable preclinical solutions that propel cardiovascular research forward. Our AAS-induced left HF model, combined with our comprehensive evaluation platforms and seasoned expertise, offers an exceptional foundation for your studies. Contact us today to discuss how we can partner to achieve your research goals.

FAQs

Q1: Why should I choose the AAS model over other HF models?

A: The AAS model offers distinct advantages due to its physiological relevance, precisely mimicking chronic pressure overload seen in clinical hypertension and aortic stenosis. Unlike acute models, it allows for the study of gradual cardiac remodeling, providing a more translatable representation of human HF progression. Its high reproducibility and low mortality rate also ensure reliable and consistent data.
Q2: What key endpoints and parameters can be measured in the AAS model?

A: We provide comprehensive evaluation, including functional parameters like ejection fraction and fractional shortening via echocardiography, and detailed pressure-volume loop analysis for contractility. Molecular markers such as gene and protein expression, histological assessments for hypertrophy (HW/BW, H&E) and fibrosis (Masson's, Picrosirius), and biochemical indicators like cardiac troponin levels are routinely measured.
Q3: Can the severity of HF be controlled in the AAS model?

A: Absolutely. The degree of pressure overload can be precisely controlled by adjusting the size of the ligature used for aortic constriction, for example, using different gauge needles (e.g., 22G or 24G). This allows for the induction of varying severities of hypertrophy and HF, enabling researchers to explore dose-dependent effects of therapies or different disease stages.
Q4: Is the AAS model suitable for studying both HFpEF and HFrEF?

A: Yes, the AAS model is versatile enough to study both HFpEF and HFrEF, depending on the timing of assessment and the specific parameters evaluated. Early phases often present with diastolic dysfunction (HFpEF characteristics), while prolonged pressure overload can lead to systolic dysfunction (HFrEF).
Q5: Does Creative Biolabs offer custom study designs for specific research needs?

A: Yes, absolutely. We understand that each research project is unique. Our scientific team works closely with clients to develop highly customized study protocols. This includes tailoring the model's parameters, selection of specific endpoints, duration of the study, and integration of specialized assays to precisely address your research objectives and maximize data utility.

Published Data

Echocardiogram results of the abdominal aortic contraction-induced HF model in rats. (OA Literature) Fig.2 Post-operation analysis of the abdominal aortic contraction-induced HF model.¹

In this study, a stable and reproducible rat HF model was successfully established. The study confirmed successful modeling at 10 weeks post-operation, evidenced by significant changes in echocardiographic parameters, increased cardiac and left ventricular mass indices, characteristic cardiac pathological staining, and elevated serum brain natriuretic peptide (BNP) levels, affirming its utility for comprehensive HF research.

Reference

Dai, Wang Sheng et al. "A Heart Failure Model Established by Pressure Overload Caused by Abdominal Aortic Contraction in Rat." Disease markers vol. 2022 4412228. 12 Oct. 2022. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.1155/2022/4412228