Isoproterenol administration induced significant, dose- and frequency-dependent myocardial injury, impaired hemodynamic function, and elevated cardiac injury markers in adult male Wistar rats.
Different dosing regimens of isoproterenol in rats produce distinct severities of myocardial necrosis, offering reliable models for preclinical myocardial injury research.
Objective: Introduction: Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. Despite advances in therapeutic strategies, ischemic heart diseases, particularly acute myocardial infarction (MI), continue to pose a serious health burden. Aim: The present study aimed to assess the impact of varying doses and dosing regimens of isoproterenol on cardiac function, myocardial remodeling, and pathological alterations in adult male Wistar rats. Design and method: Adult male Wistar rats (n = 32) were randomly divided into four groups (n = 8 each): Sham, Isoproterenol single dose (ISO-1; 85 mg/kg, s.c.), Isoproterenol two doses (ISO-2; 85 mg/kg, s.c., administered 24 hours apart), and Isoproterenol high dose (ISO-HD; 150 mg/kg, s.c.). The 85 mg/kg and 150 mg/kg regimens were used to induce acute myocardial necrosis, while a single 85 mg/kg dose was employed to produce subacute myocardial injury. On day three, hemodynamic parameters were recorded, followed by blood and heart tissue collection for biochemical, morphological, and histopathological analyses. Data were analyzed using one-way ANOVA followed by Tukey–Kramer post hoc testing. Results: Isoproterenol administration resulted in significant myocardial injury in a dose- and frequency-dependent manner. Treated groups exhibited impaired hemodynamic function, elevated serum cardiac injury markers (CK-MB, LDH), increased lipid peroxidation (MDA), and reduced antioxidant defenses (GSH, SOD, CAT). Pro-inflammatory cytokines (TNF and IL-6) were significantly elevated, and histopathological examination revealed extensive myocardial degeneration and necrosis, which were more pronounced at higher doses. Conclusions: Varying doses and dosing schedules of isoproterenol produce distinct severities of myocardial necrosis. These models provide reliable experimental platforms for studying myocardial injury and evaluating the extent of cardiac damage in preclinical research.
Bhardwaj et al. (2026) studied Myocardial necrosis (n=32). Isoproterenol vs. Sham was evaluated on Hemodynamic parameters, biochemical markers, and histopathological alterations. Isoproterenol administration induced significant, dose- and frequency-dependent myocardial injury, impaired hemodynamic function, and elevated cardiac injury markers in adult male Wistar rats.