Surgically Induced Cardiac Volume Overload by Aortic Regurgitation in Mouse
August 30th, 2022
This protocol presents a practical guide on the surgery for creation of aortic regurgitation (AR) in the mouse. Assessment of the AR mouse by echocardiography and invasive hemodynamic measurement recapitulates its clinically relevant characteristics of volume overload-induced eccentric hypertrophy, suggesting its promising application in the study of cardiac hypertrophy.
Overview
This protocol outlines a surgical method for creating aortic regurgitation in mice, which serves as a reliable model for studying volume overload-induced cardiac hypertrophy. Through echocardiographic assessments and invasive hemodynamic measurements, the study reveals significant changes in heart structure and function, offering insights into the mechanisms of volume overload cardiomyopathy.
Key Study Components
Research Area
- Cardiac hypertrophy
- Aortic regurgitation models
- Surgical techniques in animal studies
Background
- Importance of understanding volume overload in cardiac health
- Current limitations of existing methodologies
- Need for reliable experimental models
Methods Used
- Surgical creation of aortic regurgitation in mice
- Echocardiography for functional assessment
- Invasive hemodynamic measurements
Main Results
- Successful creation of aortic regurgitation leading to volume overload
- Identified cardiac structure changes such as left ventricular dilation
- Demonstrated reduced left ventricular ejection fraction and altered hemodynamic parameters
Conclusions
- This study establishes a robust model for exploring the pathological features of volume overload cardiomyopathy.
- Findings contribute to the understanding of hypertrophy mechanisms and potential therapeutic targets.
Frequently Asked Questions
Executive Industry Relevance
Reliable mouse models of aortic regurgitation (AR) are essential for dissecting the molecular mechanisms and therapeutic targets of volume overload cardiomyopathy in early discovery. This surgically induced AR model enables precise interrogation of cardiac remodeling and dysfunction, supporting predictive confidence in target validation and translational research. The approach addresses a critical gap in preclinical cardiovascular modeling, enhancing portfolio decision-making for heart failure and hypertrophy programs.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables mechanistic de-risking by distinguishing volume overload from pressure overload cardiac hypertrophy.
- Supports functional target validation through quantitative echocardiographic and hemodynamic endpoints.
- Facilitates hypothesis-driven studies on molecular pathways underlying cardiac remodeling.
Screening & Assay Development
- Provides a reproducible in vivo system for evaluating candidate interventions targeting volume overload pathology.
- Delivers standardized, quantitative readouts for left ventricular function and structure.
- Enables assay development for downstream biomarker and efficacy studies.
Translational & Preclinical Research
- Aligns preclinical findings with clinically relevant cardiac phenotypes, supporting translational biomarker strategies.
- Maintains continuity from mechanistic discovery to preclinical validation of therapeutic hypotheses.
- Informs risk-adjusted advancement of cardiovascular assets based on robust in vivo data.
Pipeline & Workflow Integration
This AR mouse model integrates into the discovery-to-preclinical continuum, bridging early mechanistic studies with translational validation for volume overload cardiomyopathy.
- Discovery Biology: Supports null hypothesis testing and pathway clarification for cardiac remodeling mechanisms.
- Screening: Provides reproducible, quantitative endpoints for functional and structural cardiac assessment.
- Analytics: Enables statistical comparison of intervention effects using echocardiographic and hemodynamic data.
- Translational Research: Connects preclinical cardiac phenotypes to clinical disease features for biomarker alignment.
- Enterprise Reuse: Establishes a standardized platform for comparative studies and cross-program evaluation.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in cardiac target validation.
- Operational Value: Delivers reproducible, scalable, and standardized in vivo modeling for cardiovascular research.
- Strategic Value: Improves go/no-go decisions and capital allocation by providing robust preclinical evidence.
- Portfolio Impact: Enables risk-adjusted prioritization of cardiovascular discovery and development programs.
Implementation Considerations
- Requires expertise in high-resolution echocardiography and microsurgical techniques.
- Demands access to specialized imaging and hemodynamic instrumentation.
- Necessitates cross-team standardization for reproducibility and data comparability.
- Adaptation may be needed for different mouse strains or comorbid models.
- Perioperative mortality and technical complexity must be managed for consistent outcomes.
Biopharma FAQs
Chapters in this video
0:00
Introduction
1:10
Preparation for Ultrasound Imaging (Mandatory) and Invasive Hemodynamic Measurement (Optional)
1:42
Preparation of Surgical Devices and Isolation of the RCCA
2:21
Catheterization Through the RCCA and Ascending Aorta Under Ultrasound Guidance
3:44
Puncture of the Aortic Valves under Ultrasound Guidance
4:48
Withdrawal of the Plastic Catheter, Metal Wire, and Perioperative Care
5:19
Assessment of Aortic Valve Perforation, Cardiac Morphology, and Function using Echocardiography and Invasive Hemodynamic Measurement
6:11
Results
7:45
Conclusion
