{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:23:19Z","timestamp":1788877399186,"version":"build-2803163510"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anhui Engineering Technology Research Center of Biochemical Pharmaceutical Foundation","award":["2023SYKFD06"],"award-info":[{"award-number":["2023SYKFD06"]}]},{"name":"the Key Projects of Outstanding Young Talents Support Program in Universities of Anhui Province","award":["YQZD2024029"],"award-info":[{"award-number":["YQZD2024029"]}]},{"name":"Bengbu Medical University 2024 Graduate Student Research and Innovation Program Funding Established Projects","award":["Byycx24065"],"award-info":[{"award-number":["Byycx24065"]}]},{"name":"Bengbu Medical University Student Innovation and Entrepreneurship Training Program Project","award":["bydc2024011"],"award-info":[{"award-number":["bydc2024011"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Heart failure (HF) modeling requires standardized protocols to ensure translational relevance. Despite the widespread use of isoproterenol (ISO)\u2014a \u03b2-adrenergic agonist\u2014in 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\u20138 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.<\/jats:p>","DOI":"10.1371\/journal.pone.0334880","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T18:22:53Z","timestamp":1762194173000},"page":"e0334880","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Heart failure induced by isoproterenol: A comparison of two doses and two delivery methods in C57BL\/6J 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