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Updated: Aug 19, 2025
Author Spotlight: Investigating HR-Dependent Cardiac Function in Mouse Models Through a Novel Atrial-Pacing Approach
Published on: July 21, 2023
Assessing systolic and diastolic reserves in male and female mice
B Coyle-Asbil1,2, E J B Holjak1,2, J P Marrow1,2
1Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Insights
Assessing cardiac reserve in mice is challenging. This study found current methods fail to measure diastolic reserve in vivo and highlights sex differences in systolic reserve assessment.
Area of Science:
- Cardiovascular Physiology
- Preclinical Research Models
- Sex Differences in Health
Background:
- Cardiac reserve, a key health and prognostic indicator, is well-established clinically but lacks standardization in preclinical models.
- While cardiac reserve includes both systolic (contractile) and diastolic (relaxation) components, diastolic reserve receives less research focus.
- Standardized methods for assessing cardiac reserve, particularly diastolic reserve, in preclinical settings are needed.
Purpose of the Study:
- To determine the most effective techniques (echocardiography, invasive hemodynamics, Langendorff) for assessing systolic and diastolic reserves in preclinical models.
- To investigate the impact of sex on the assessment of systolic and diastolic reserves.
- To identify reliable parameters for evaluating cardiac reserve components in mice.
Main Methods:
- Healthy adult male and female CD-1 mice were utilized.
- Dobutamine was administered to induce physiological stress.
- Echocardiography, invasive hemodynamics, and Langendorff techniques were employed to assess cardiac function.
- Systolic and diastolic reserves were evaluated using various established parameters.
Main Results:
- Systolic reserve can be reliably assessed using all tested techniques (echocardiography, invasive hemodynamics, Langendorff) in vivo and in vitro.
- Current in vivo indices are insufficient for accurately measuring diastolic reserve in healthy adult mice.
- Sex significantly influences the dose-response of echocardiography parameters (e.g., fractional shortening, ejection fraction) used for systolic reserve assessment.
Conclusions:
- Established in vivo methods are inadequate for assessing diastolic cardiac reserve in healthy adult mice.
- Systolic reserve assessment is feasible across multiple techniques, but sex-specific responses must be considered.
- This study provides crucial insights into sex differences in cardiac reserve assessment and establishes a foundation for improved preclinical methodologies.
Abstract:
Cardiac reserve is a widely used health indicator and prognostic tool. Although it is well established how to assess cardiac reserve clinically, in preclinical models, it is more challenging lacking standardization. Furthermore, although cardiac reserve incorporates both systolic (i.e., contractile reserve) and diastolic (i.e., relaxation reserve) components of the cardiac cycle, less focus has been placed on diastolic reserve. The aim of our study was to determine which technique (i.e., echocardiography, invasive hemodynamic, and Langendorff) and corresponding parameters can be used to assess the systolic and diastolic reserves in preclinical models. Healthy adult male and female CD-1 mice were administered dobutamine and evaluated by echocardiography and invasive hemodynamic, or Langendorff to establish systolic and diastolic reserves. Here, we show that systolic reserve can be assessed using all techniques in vivo and in vitro. Yet, the current indices available are ineffective at capturing diastolic reserve of healthy mice in vivo. When assessing systolic reserve, sex affects the dose response of several commonly used echocardiography parameters [i.e., fractional shortening (FS), ejection fraction (EF)]. Taken together, this study improves our understanding of how sex impacts the interpretation assessment of cardiac reserve and establishes for the first time that in healthy adult mice, the diastolic reserve cannot be assessed by currently established methods in vivo.NEW & NOTEWORTHY Cardiac reserve is a globally used health indicator and prognostic tool that is used by clinicians and preclinical scientists. In physiology, we have a long-standing appreciation of how to assess systolic reserve but lack insight into sex differences and have no frame of reference for measuring diastolic reserve to certainty across cardiac techniques or the influence of sex. Here, we show that the primary means for assessing diastolic reserve is incorrect. Furthermore, we provided proof and clarity on how to correctly measure systolic and diastolic reserve capacities. We also highlight the imperative of sex differences to the measures of both systolic and diastolic reserves using several techniques (i.e., echocardiography, invasive hemodynamics, and Langendorff) in mice.
