Journal Article

Heart failure induced by isoproterenol: A comparison of two doses and two delivery methods in C57BL/6J mice

Zhang, Mengxiao, Yang, Rong, Yu, Aonan, Yang, Peng, Ye, Yuqing, Huang, Shaojie, Wang, Yaojiang, Zhu, Chunxiao

2025

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adrenergic beta-Agonists - administration & dosage / Animals / Cardiac function / Cardiomyocytes / Congestive heart failure / Disease Models, Animal / Dosage / Dose-Response Relationship, Drug / Drug dosages / Echocardiography / Factorial design / Fibrosis / Heart failure / Heart Failure - chemically induced / Heart Failure - diagnostic imaging / Heart Failure - pathology / Heart Failure - physiopathology / Hypertrophy / Injections, Intraperitoneal / Injections, Subcutaneous / IP (Internet Protocol) / Isoproterenol / Isoproterenol - administration & dosage / Isoproterenol - adverse effects / Male / Mice / Mice, Inbred C57BL / Modelling / Mortality / Natriuretic Peptide, Brain - blood / Peptides / Phenotypes / Rodents / Statistical significance / Survival analysis / Sympathomimetics / Ventricular Remodeling - drug effects