Q1: How quickly does HF develop in the ACF model, and what is its typical progression?

In the ACF model, the onset and progression of HF are remarkably predictable. Measurable signs of cardiac dysfunction and remodeling typically begin within 4 to 6 weeks post-fistula creation in rats, advancing to overt HF over several months, allowing for both acute and chronic intervention studies.

Q2: What is the primary difference between the ACF model and other common HF models, such as pressure overload models (e.g., TAC)?

The ACF model primarily induces HF through chronic volume overload, mimicking high-output HF, where the heart struggles with excessive blood return. In contrast, pressure overload models, like Transverse Aortic Constriction (TAC), simulate conditions where the heart faces increased resistance to blood ejection, leading to different forms of cardiac stress and remodeling.

Q3: Can the ACF model be used to study both left and right ventricular HF?

Absolutely. The ACF model induces a significant volume overload on both the left and right ventricles. This leads to biventricular hypertrophy and dysfunction, making it an excellent platform for investigating the interplay between left and right HF and the broader consequences of systemic volume stress.

Q4: Can you help with customized experimental designs, such as specific treatment regimens or combination therapies?

Our team excels at tailoring study designs to client-specific needs. Whether you require unique treatment regimens, combination therapies, or specialized endpoints, we work closely with you to develop and execute customized protocols that align precisely with your research objectives, ensuring optimal data generation.

Q5: How does Creative Biolabs ensure the reproducibility and quality of data generated from the ACF model?

Reproducibility is paramount at Creative Biolabs. We achieve this through standardized surgical procedures, strict adherence to established protocols, rigorous quality control checks on all measurements, and the use of experienced scientific personnel. Our data undergoes thorough statistical analysis to ensure robustness and reliability.

Q6: Are there any ethical considerations or specific regulatory requirements associated with using the ACF model?

All animal studies at Creative Biolabs adhere to the highest ethical standards and comply with all relevant national and international regulatory guidelines, including those set by institutional animal care and use committees (IACUC). Our animal facilities are fully accredited, ensuring humane and responsible animal research practices.

ACF induced Anterior Pressure Overload Heart Failure Modeling & Pharmacodynamics Service

Creative Biolabs stands at the forefront of this effort, providing a diverse array of well-established and meticulously characterized rodent HF models to accelerate your drug discovery and development programs.

Introduction

Heart failure (HF) continues to be a devastating global health challenge, marked by complex progression and significant mortality. Developing effective therapies necessitates robust and clinically relevant preclinical models that accurately replicate disease mechanisms and facilitate the rigorous evaluation of novel interventions.

ACF-Induced Anterior Pressure Overload HF Model

The aortocaval fistula (ACF) model represents a gold standard for investigating volume-overload HF and its associated pulmonary complications. It involves creating a direct shunt between the abdominal aorta and the inferior vena cava, inducing a predictable and progressive cardiac remodeling process.

A schematic description of the creation of ACF in rats, an experimental model of volume-overload CHF. (OA Literature) Fig.1 Schematic description of the creation of ACF in the volume-overload congestive HF (CHF) rat model.¹

Model Construction Steps

The construction of the ACF model is a precise surgical procedure designed to induce chronic volume overload:

01Preparation

Animals are anesthetized, and the abdominal cavity is carefully opened to expose the infrarenal abdominal aorta and inferior vena cava (IVC).

02Vessel Isolation and Clamping

Both the aorta and IVC are meticulously isolated, and a clamp is temporarily placed across both vessels distal to the renal arteries.

03Fistula Creation

An 18-gauge needle (or 16-gauge for accelerated CHF development) is introduced into the lateral wall of the aorta, then advanced medially to puncture through the aortic wall and into the adjacent wall of the IVC.

04Needle Withdrawal and Sealing

The needle is gently withdrawn, ensuring the creation of a patent fistula. The entry point in the aortic wall is then sealed using cyanoacrylate adhesive.

05Recovery

The abdominal wall is closed, and the animals are provided with appropriate pain management and care during recovery.

Strengths and Limitations

Strengths:

Physiological Mimicry: The model faithfully recapitulates key hemodynamic and pathophysiological hallmarks of volume-overload HF and its systemic complications, including pulmonary arterial hypertension (PAH).
Reproducibility & Predictability: When performed with refined surgical techniques, the ACF model consistently induces quantifiable signs of HF within a defined timeframe, allowing for precise experimental design.
Cost-Effectiveness: Utilizing rodent species makes the ACF model a more economical and higher-throughput alternative compared to larger animal models.
Diverse Pathological Study: Enables the comprehensive investigation of cardiac hypertrophy, ventricular dilation, myocardial fibrosis, systolic and diastolic dysfunction, neurohumoral activation, and pulmonary vascular remodeling.
Genetic Adaptability: Highly compatible with genetically modified mice, offering an unparalleled platform for dissecting molecular mechanisms and validating novel gene targets.

Limitations:

Surgical Skill Dependence: The successful creation of a reproducible fistula requires significant surgical expertise to minimize perioperative complications such as bleeding.
Variability in CHF Onset (Historical): Earlier methodologies (e.g., smaller needle gauges) sometimes led to inconsistent HF development; however, modified approaches have largely overcome this, ensuring predictable progression.
In Vitro-In Vivo Translation Challenges: While in vitro stretch models provide mechanistic insights, scaling up protein accumulation for analysis on in vitro stretch membranes can be challenging, requiring careful experimental design to link findings to in vivo outcomes.

Evaluation Platform

Creative Biolabs provides a comprehensive suite of advanced evaluation platforms to characterize disease progression and assess therapeutic efficacy in the ACF model. Our capabilities span:

Imaging: Echocardiography (LV/RV dimensions, ejection fraction, fractional shortening), Pressure-Volume (PV) loops (contractility, relaxation, preload, afterload).
Histopathology: H&E staining, Masson's Trichrome (fibrosis), Picrosirius Red (collagen quantification), immunofluorescence (cellular markers, inflammation, protein expression).
Molecular Analysis: qRT-PCR (gene expression of hypertrophy, fibrosis, inflammatory markers, ECM components like COLIA1/COLIA2, Notch pathway), Western Blotting (protein expression, phosphorylation states), ELISA (circulating biomarkers).
Biochemical Assays: Plasma BNP, ANP, inflammatory cytokines, renal function markers.
Behavioral Assessment: Activity monitoring, exercise tolerance tests (if applicable).

Applications

Disease Modeling: Accurately simulates chronic volume-overload HF, including cardiac hypertrophy, ventricular remodeling, systolic and diastolic dysfunction, associated PAH, and neurohumoral activation.
Therapeutic Efficacy Testing: Ideal for evaluating novel drug candidates, including anti-remodeling agents, hemodynamic modulators, anti-inflammatory compounds, organ-protective therapies, and various gene therapies.
Treatment Strategy Optimization: Facilitates the study of pharmacological interventions, genetic manipulations (gene silencing, overexpression), and the synergistic effects of combination therapies to refine therapeutic approaches.

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

Abdominal Aortic Stenosis induced Left HF 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

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

Deep Scientific Acumen: Years of specialized experience in cardiovascular biology and preclinical model development.
Customized Study Design: Tailored ACF model protocols and endpoints to precisely meet your specific research objectives.
Comprehensive Characterization: State-of-the-art phenotyping capabilities for robust and meaningful data generation.
Translational Expertise: Skillful interpretation of preclinical findings into actionable insights for human therapeutic development.
Quality and Compliance: Strict adherence to ethical guidelines and rigorous quality assurance protocols, ensuring reliable and compliant data.

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 provides comprehensive research services utilizing the ACF-induced HF model. We invite you to contact us to explore how our expertise can advance your cardiovascular research goals and accelerate your next breakthrough.

FAQs

Q1: How quickly does HF develop in the ACF model, and what is its typical progression?

A: In the ACF model, the onset and progression of HF are remarkably predictable. Measurable signs of cardiac dysfunction and remodeling typically begin within 4 to 6 weeks post-fistula creation in rats, advancing to overt HF over several months, allowing for both acute and chronic intervention studies.
Q2: What is the primary difference between the ACF model and other common HF models, such as pressure overload models (e.g., TAC)?

A: The ACF model primarily induces HF through chronic volume overload, mimicking high-output HF, where the heart struggles with excessive blood return. In contrast, pressure overload models, like Transverse Aortic Constriction (TAC), simulate conditions where the heart faces increased resistance to blood ejection, leading to different forms of cardiac stress and remodeling.
Q3: Can the ACF model be used to study both left and right ventricular HF?

A: Absolutely. The ACF model induces a significant volume overload on both the left and right ventricles. This leads to biventricular hypertrophy and dysfunction, making it an excellent platform for investigating the interplay between left and right HF and the broader consequences of systemic volume stress.
Q4: Can you help with customized experimental designs, such as specific treatment regimens or combination therapies?

A: Our team excels at tailoring study designs to client-specific needs. Whether you require unique treatment regimens, combination therapies, or specialized endpoints, we work closely with you to develop and execute customized protocols that align precisely with your research objectives, ensuring optimal data generation.
Q5: How does Creative Biolabs ensure the reproducibility and quality of data generated from the ACF model?

A: Reproducibility is paramount at Creative Biolabs. We achieve this through standardized surgical procedures, strict adherence to established protocols, rigorous quality control checks on all measurements, and the use of experienced scientific personnel. Our data undergoes thorough statistical analysis to ensure robustness and reliability.
Q6: Are there any ethical considerations or specific regulatory requirements associated with using the ACF model?

A: All animal studies at Creative Biolabs adhere to the highest ethical standards and comply with all relevant national and international regulatory guidelines, including those set by institutional animal care and use committees (IACUC). Our animal facilities are fully accredited, ensuring humane and responsible animal research practices.

Published Data

Fig.2 Characterization of the ACF animal model: right heart hypertrophy, collagen accumulation and PA fibrosis.²

In this study, the ACF rat model successfully induced chronic vascular volume overload, leading to PAH characterized by increased collagen accumulation in the pulmonary artery adventitial layer, mirroring observations in human PAH-CHD patients. The research further elucidated the role of cyclic mechanical stretch and Notch signaling in modulating this vascular remodeling, highlighting the model's capacity to reveal critical disease mechanisms and provide insights for preventing abnormal matrix protein synthesis in volume overload-induced PH.

References

Abassi, Zaid et al. "Aortocaval fistula in rat: a unique model of volume-overload congestive heart failure and cardiac hypertrophy." Journal of biomedicine & biotechnology vol. 2011 (2011): 729497. Distributed under Open Access license CC BY 3.0, without modification. https://doi.org/10.1155/2011/729497
Chang, Chi-Jen et al. "Remodeling Matrix Synthesis in a Rat Model of Aortocaval Fistula and the Cyclic Stretch: Impaction in Pulmonary Arterial Hypertension-Congenital Heart Disease." International journal of molecular sciences vol. 21,13 4676. 30 Jun. 2020. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/ijms21134676