Assessing systolic and diastolic reserves in male and female mice

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 pre clinical 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 influ-ence 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.