ArticlePloS one2025
Heart failure induced by isoproterenol: A comparison of two doses and two delivery methods in C57BL/6J mice.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cardiorenal Associations in Preclinical Modeling: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- P2X7-NEK7-NLRP3 Axis Drives Cardiac Inflammation and Fibrosis in Isoproterenol-Induced Cardiac Remodeling in Mice.Acta physiologica (Oxford, England) · 2026Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heart failure (HF) modeling requires standardized protocols to ensure translational relevance. Despite the widespread use of isoproterenol (ISO)-a β-adrenergic agonist-in HF modeling, methodological inconsistencies in dosing and administration routes limit reproducibility. This study evaluated the effects of subcutaneous (SC) and intraperitoneal (IP) administration of ISO at two literature-established doses (5 and 60 mg/kg/day for 14 days) on cardiac remodeling in C57BL/6J mice, aiming to identify the optimal protocol for HF modeling. Using a factorial design, male C57BL/6J mice aged 6-8 weeks were divided into six cohorts: (1) SC saline control, (2) IP saline control, (3) SC 5 mg/kg ISO, (4) IP 5 mg/kg ISO, (5) SC 60 mg/kg ISO, and (6) IP 60 mg/kg ISO, with daily administration for 14 days. High-dose ISO (60 mg/kg/day) induced a 25% mortality rate in both SC and IP cohorts, yet IP administration exhibited marked inter-individual variability, undermining model reliability. Echocardiography revealed SC 5 mg/kg group induced stable systolic dysfunction accompanied by left ventricular dilation, while maintaining 100% survival. This cohort also displayed significantly elevated hypertrophy indices. Histopathological quantification suggested that SC 60 mg/kg induced extensive fibrosis. All ISO-treated groups showed upregulated myocardial hypertrophy markers and approximately 2-fold elevation in serum NT-proBNP levels. In summary, SC 5 mg/kg/day regimen not only ensures reliable phenotype induction but also reduces animal attrition, offering a robust platform for investigating CHF mechanisms and accelerating therapeutic development.
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