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Author Spotlight: Investigating HR-Dependent Cardiac Function in Mouse Models Through a Novel Atrial-Pacing Approach
Published on: July 21, 2023
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A pacing-controlled protocol for frequency-diastolic relations distinguishes diastolic dysfunction specific to a
Genri Numata1,2, Eiki Takimoto1,3, Taro Kariya4
1Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, Japan.
American Journal of Physiology. Heart and Circulatory Physiology
|August 12, 2022
Summary
A new pacing-controlled pressure-volume loop protocol effectively detects diastolic dysfunction in mouse models of heart failure with preserved ejection fraction (HFpEF). This method reveals impairments not apparent under resting conditions, advancing HFpEF research.
Area of Science:
- Cardiovascular Physiology
- Animal Models of Disease
- Diastolic Dysfunction Research
Background:
- Heart failure with preserved ejection fraction (HFpEF) is a growing global health concern, characterized by diastolic dysfunction and reduced exercise capacity.
- A significant challenge in HFpEF research is the lack of reliable methods to detect diastolic dysfunction in mouse models.
- Existing methods may fail to identify diastolic abnormalities under resting conditions, necessitating dynamic assessment.
Purpose of the Study:
- To develop and validate a pacing-controlled pressure-volume (PV) loop protocol for assessing diastolic function in mice at various heart rates.
- To determine if this protocol can specifically detect diastolic dysfunction in a murine model of HFpEF.
- To compare the protocol's efficacy in HFpEF, pressure-overload (PO) models, and control mice.
Main Methods:
- Developed a heart rate (HR) manipulation strategy using ivabradine to slow HR below 400 beats/min.
- Employed atrial pacing via an esophageal catheter to incrementally increase HR from 400 to 700 beats/min.
- Acquired and analyzed PV loop data to assess diastolic parameters including relaxation time constant (Tau) and end-diastolic pressure-volume relationship (EDPVR).
Main Results:
- No diastolic abnormalities were detected in HFpEF or PO models at baseline without pacing.
- The pacing-controlled protocol revealed significant diastolic impairment specific to the HFpEF model, with worsened Tau and EDPVR at higher HRs.
- Peak positive dP/dt (a measure of systolic function) was reduced in HFpEF mice only at the highest paced HR (700 beats/min).
Conclusions:
- A pacing-controlled PV loop protocol is a feasible and potent method for detecting diastolic dysfunction in mouse models of HFpEF.
- This technique uncovers diastolic impairments that are masked under resting conditions, offering new insights into HFpEF pathophysiology.
- The protocol enables precise characterization of diastolic function across a range of physiological heart rates in experimental models.
