Ein schrittmachergesteuertes Verfahren zur Beurteilung herzfrequenzabhängiger diastolischer Funktionen in murinen Herzinsuffizienzmodellen

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.

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