Key result
Mice with induced mild HFpEF exhibited increased vulnerability to reduced preload ex vivo, indicating that elevated left ventricular filling pressure compensated for a rigid left ventricle.
Why the study?
HFpEF pathophysiology remains poorly understood, and animal models are challenging due to difficulties in assessing heart failure severity in small animals.
A mouse model of mild HFpEF induced by Western diet and NO synthase inhibition demonstrates preload dependence, providing a valuable tool for studying early disease progression.
New mouse HFpEF model aids preload research; leaves open clinical translation and validation.
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.
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Jacobsen et al. (2024) studied Heart Failure with preserved Ejection Fraction (HFpEF). Western diet and NO synthase inhibition vs. Control mice was evaluated on Preload dependence ex vivo. Mice with induced mild HFpEF exhibited increased vulnerability to reduced preload ex vivo, indicating that elevated left ventricular filling pressure compensated for a rigid left ventricle.
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