Echocardiographic evaluation of cardiac reserve to detect subtle cardiac dysfunction in mice

Cardiac reserve is a sensitive tool for early detection of cardiac dysfunction. However, cardiac reserve assessment by catecholamine stress echocardiography in mice varied in the doses of β-adrenergic agonists and the time point for measurements, which may lead to inaccurate readouts. This study aims to establish a standardized protocol for assessing cardiac reserve in mice. C57BL/6J mice under isoflurane anesthesia were intraperitoneally injected with varying doses of isoproterenol (Iso), and subjected to echocardiographic measurements. Heart rate (HR), ejection fraction (EF), fractional shortening (FS), global longitudinal strain (GLS) and strain rate all reached peak values within 1–3 min after Iso injection at doses higher than 0.2 mg/kg. Compared with 0.1 mg/kg Iso, 0.2 mg/kg Iso resulted in higher HR, EF, FS and GLS, whereas doses higher than 0.2 mg/kg did not yield further increase. Cardiac response of female mice recapitulated main characteristics of those of male mice except that female mice displayed higher maximum HR and were more sensitive to higher doses of Iso. Furthermore, the advantages of present stress protocol over conventional baseline echocardiographic measurements were verified in comparisons of exercised vs. sedentary and aged vs. young mice for cardiac function evaluation. We developed a reproducible and sensitive approach to evaluate cardiac reserve by continuously monitoring cardiac function every minute for 3 min after 0.2 mg/kg Iso injection. This approach will enable detection of subtle cardiac dysfunction and accelerate innovative research in cardiac pathophysiology.