A Pacing-Controlled Procedure for the Assessment of Heart Rate-Dependent Diastolic Functions in Murine Heart Failure Models
July 21st, 2023
The present protocol describes obtaining the pressure-volume relationship through transesophageal pacing, which serves as a valuable tool in evaluating diastolic function in mouse models of heart failure.
The heart rate-related relationship is important for determining cardiac characteristics, particularly, in HFpEF. This protocol aims to assess heart rate-dependent cardiac function. Any experimental models, available modalities for assessing heart rate-related cardiac function, are limited to treadmill exercise testing.
The treadmill test, however, is influenced by variables such as body weight. To overcome these limitations, we have developed around atrial-pacing protocol to detect subtle, yet significant changes in the later performance that are linked to heart rate. Our protocol offers a variable tool for identifying cardiac dysfunction, manifested by heart rate changes.
It also presents a number approach to studying diastolic dysfunction in mirroring heart failure models, particularly in HFpEF.
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Overview
This study presents a protocol for assessing the pressure-volume relationship through transesophageal pacing in mouse models of heart failure, particularly focusing on the diastolic function. The protocol is designed to detect subtle changes in heart performance related to heart rate.
Key Study Components
Research Area
- Cardiac function assessment
- Heart failure models
- Diastolic dysfunction evaluation
Background
- Heart rate influence on cardiac characteristics
- Limitations of treadmill exercise testing
- Need for improved assessment methods for heart function
Methods Used
- Atrial pacing protocol
- Mouse models of heart failure
- Transesophageal pacing technology
Main Results
- Successfully identified cardiac dysfunction linked to heart rate changes
- Demonstrated subtle performance changes in heart function
- Validated the approach for studying diastolic dysfunction
Conclusions
- The protocol effectively evaluates diastolic function in heart failure models
- Offers a novel approach to studying heart rate-dependent cardiac functions
Frequently Asked Questions
Executive Industry Relevance
Heart failure with preserved ejection fraction (HFpEF) presents a major translational challenge due to the complexity of diastolic dysfunction and the limitations of conventional preclinical assessment tools. This pacing-controlled protocol enables precise, heart rate-dependent evaluation of diastolic function in murine models, directly addressing the need for mechanistic de-risking and predictive confidence in early cardiovascular drug discovery. By isolating cardiac performance from confounding variables, the method strengthens target validation and informs risk-adjusted portfolio decisions.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables interrogation of heart rate-dependent diastolic dysfunction in disease-relevant murine models.
- Supports mechanistic de-risking by isolating cardiac-specific effects from systemic influences.
- Improves predictive confidence for target validation in HFpEF research pipelines.
Screening & Assay Development
- Facilitates preparation of validated cardiac function assays for downstream compound screening.
- Delivers reproducible, quantitative pressure-volume loop outputs across controlled heart rate increments.
- Enables standardization of diastolic function assessment, supporting scalable screening workflows.
Translational & Preclinical Research
- Aligns preclinical cardiac phenotyping with human HFpEF pathophysiology by focusing on diastolic impairment.
- Provides continuity from early discovery through preclinical validation of cardiac targets.
- Supports risk-adjusted advancement decisions by quantifying heart rate-dependent dysfunction.
Pipeline & Workflow Integration
This protocol integrates into the discovery-to-preclinical continuum by enabling robust, quantitative assessment of diastolic function in murine HFpEF models.
- Discovery Biology: Supports hypothesis testing and mechanistic clarification of heart rate-dependent cardiac dysfunction.
- Screening: Provides assay-ready, reproducible pressure-volume loop data for compound evaluation.
- Analytics: Generates quantitative outputs such as Tau and EDPVR for comparative analysis across experimental conditions.
- Translational Research: Bridges preclinical findings with clinical HFpEF endpoints by modeling diastolic impairment under controlled pacing.
- Enterprise Reuse: Establishes a reusable platform for cardiac function assessment in diverse heart failure models.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in cardiac target validation.
- Operational Value: Enhances standardization, reproducibility, and scalability of diastolic function assays.
- Strategic Value: Informs go/no-go decisions and improves capital efficiency by de-risking early cardiac programs.
- Portfolio Impact: Enables risk-adjusted prioritization and advancement of cardiovascular assets.
Implementation Considerations
- Requires expertise in murine cardiac surgery and pressure-volume loop analysis.
- Demands specialized instrumentation for atrial pacing and conductance catheterization.
- Necessitates cross-team standardization of data acquisition and analysis protocols.
- Adaptation may be needed for different heart failure models or pacing parameters.
- Potential limitations include anesthesia effects and technical variability in catheter placement.
Biopharma FAQs
Chapters in this video
0:00
Introduction
1:15
Instrument and Animal Preparation for Catheterization in a Murine Heart Failure Model
2:35
Surgical Procedure for Left Ventricular Catheterization (Open Chest Approach) in a Murine Heart Failure Model
3:37
Determining the End‐Systolic and End‐Diastolic Pressure‐Volume Relationships in a Murine Heart Failure Model and Transesophageal Pacing
6:42
Saline Calibration and Aortic Flow Calibration in a Murine Heart Failure Model
