Effects of anesthetic agents on the evaluation of systolic and diastolic function in mice

Aim: This study aimed to optimize non-invasive echocardiographic evaluation of myocardial function in a mouse model of diastolic heart failure, emphasizing the methodological challenges in assessing diastolic and left atrial (LA) function. Recognizing that clinical human studies frequently assess cardiac performance in non-sedated subjects, this investigation compared systolic and diastolic functional outcomes in mice subjected to heart failure with preserved ejection fraction (HFpEF) using two anesthetic agents: Avertin (mild sedation) and isoflurane (deep sedation). Additionally, we present a histological and echocardiographic correlation of the LA changes in established HFpEF mouse model. Results: Mice received angiotensin II and phenylephrine (AngII/PE) infusions for 28 days, followed by comprehensive echocardiographic and histologic analysis, including advanced diastology and LA assessment. AngII/PE treatment produced a reproducible HFpEF phenotype, with multiorgan involvement. Cardiac function measurements revealed significantly greater declines in both systolic and diastolic function in isoflurane-sedated mice, while mice sedated with Avertin primarily exhibited worsening diastolic metrics. LA histology corroborated imaging findings, showing profound wall thinning, reduced cellularity, and fibrotic conversion by day 28, changes tightly linked to deteriorating diastolic performance. Conclusion: The study highlights the limitations of deep sedation in accurately reflecting physiological cardiac function and underscores the importance of standardized mild-sedation protocols for translational murine heart failure research. Unlike the ventricular thickening and cardiomyocyte hypertrophy typically seen with diastolic dysfunction, LA remodeling was characterized by myocardial thinning and fibrosis, suggesting a distinct and opposite to LV pathogenic process. These findings support prioritizing minimally sedated echocardiographic assessment for better translational relevance.