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Updated: May 20, 2025
Implantation of an Isoproterenol Mini-Pump to Induce Heart Failure in Mice
Published on: October 3, 2019
Co-administration of isoprenaline and phenylephrine induced a new HFrEF mouse model through activation of both SNS
Huimin Su1, Ming Liu2, Siteng Wang3
1Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Introduction:
The pathogenesis of human heart failure is diverse, and a large number of animal models have emerged to better understand the development of heart failure in humans. Among them, there are several methods of induction in mouse heart failure models, each with its advantages and disadvantages. The use of drug induced heart failure models has greatly facilitated basic research and reduced the disadvantages of time-consuming and labor-intensive surgical modeling.
Methods:
In our experiments, we used a combination of isoprenaline (ISO) and phenylephrine (PE) for modeling; we aimed to evaluate whether it is superior to conventional drug-induced models, especially those induced by isoprenaline alone. The ISO and PE were administered for 2 weeks by subcutaneous implantation with a micro-osmolar pump, and the mice were monitored dynamically for cardiac ultrasound and blood pressure.
Results:
RNA sequencing of myocardial tissues after execution of mice further clarified that hypertrophy, fibrosis genes, Sympathetic nervous system (SNS), and Renin-angiotensin-aldosterone system (RAAS) pathways were upregulated.
Discussion:
Therefore, we conclude that the ISO/PE-induced mouse heart failure model can activate both the SNS and RAAS, through the activation of both α-adrenergic receptor (α-AR) and β-adrenergic receptor (β-AR), which is more consistent with the development of human heart failure than the ISO-induced model and is expected to be a unique and representative heart failure modeling method.
Insights
A new mouse model using isoprenaline and phenylephrine (ISO/PE) effectively mimics human heart failure by activating sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) pathways.
Area of Science:
- Cardiovascular Research
- Animal Models of Disease
- Molecular Biology
Background:
- Human heart failure pathogenesis is complex, necessitating robust animal models.
- Drug-induced models offer advantages over surgical methods in time and labor.
- Isoprenaline (ISO)-induced models are common but may not fully recapitulate human disease.
Purpose of the Study:
- To evaluate a novel drug-induced mouse heart failure model using a combination of isoprenaline (ISO) and phenylephrine (PE).
- To compare the efficacy of the ISO/PE model against conventional ISO-alone models.
- To assess the model's ability to mimic key human heart failure pathways.
Main Methods:
- Mice were treated with ISO and PE via subcutaneous micro-osmolar pumps for two weeks.
- Cardiac ultrasound and blood pressure were monitored dynamically throughout the study.
- RNA sequencing was performed on myocardial tissues post-mortem.
Main Results:
- The ISO/PE model led to upregulation of hypertrophy and fibrosis-related genes.
- Key pathways including the Sympathetic Nervous System (SNS) and Renin-Angiotensin-Aldosterone System (RAAS) were activated.
- RNA sequencing confirmed significant molecular changes in myocardial tissues.
Conclusions:
- The ISO/PE mouse model activates both SNS and RAAS pathways via alpha- and beta-adrenergic receptors.
- This model more closely resembles human heart failure pathogenesis than ISO-alone models.
- The ISO/PE model represents a unique and representative method for heart failure research.
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