Abstract
Aim: Heart Failure with preserved Ejection Fraction (HFpEF) is characterized by diastolic dysfunction and reduced cardiac output, but its pathophysiology remains poorly understood. Animal models of HFpEF are challenging due to difficulties in assessing the degree of heart failure in small animals. This study aimed at inducing HFpEF in a mouse model to probe preload-dependency. Methods: Increased body mass and arterial hypertension were induced in mice using a Western diet and NO synthase inhibition. Preload dependence was tested ex vivo. Results: Mice with obesity and hypertension exhibited reduced cardiac output, indicating a failing heart. Increased left ventricular filling pressure during diastole suggested reduced compliance. Notably, the ejection fraction was preserved, suggesting the development of HFpEF. Spontaneous physical activity at night was reduced in HFpEF mice, indicating exercise intolerance; however, the cardiac connective tissue content was comparable between HFpEF and control mice. The HFpEF mice showed increased vulnerability to reduced preload ex vivo, indicating that elevated left ventricular filling pressure compensated for the rigid left ventricle, preventing a critical decrease in cardiac output. Conclusion: This animal model successfully developed mild HFpEF with a reduced pump function that was dependent on a high preload. A model of mild HFpEF may serve as a valuable tool for studying disease progression and interventions aimed at delaying or reversing symptom advancement, considering the slow development of HFpEF in patients.
Originalsprog | Engelsk |
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Artikelnummer | e14099 |
Tidsskrift | Acta Physiologica |
Vol/bind | 240 |
Udgave nummer | 3 |
Antal sider | 15 |
ISSN | 1748-1708 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:Financial support was provided by the Independent Research Fund Denmark, DFF grant ID: 10.46540/2034‐00073B (to Dr Thomsen). Telemetry recordings were performed by the Telemetry Unit for Cardiovascular Phenotyping at the University of Copenhagen, supported by the Novo Nordisk Foundation (grant agreement number NNF18OC0032728 to Dr Thomsen). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Publisher Copyright:
© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.