Effect of injection of different doses of isoproterenol on the hearts of mice

Abstract

Background Heart failure (HF) is one of the diseases that seriously threaten human health today and its mechanisms are very complex. Our study aims to confirm the optimal dose ISO-induced chronic heart failure mice model for better study of HF-related mechanisms and treatments in the future. Methods C57BL/6 mice were used to establish mice model of chronic heart failure. We injected isoproterenol subcutaneously in a dose gradient of 250 mg/kg, 200 mg/kg, 150 mg/kg, 100 mg/kg and 50 mg/kg. Echocardiography and ELISA were performed to figure out the occurrence of HF. We also supplemented the echocardiographic changes in mice over 30 days. Results Except group S and group E, echocardiographic abnormalities were found in other groups, suggesting a decrease in cardiac function. Except group S, myofibrolysis were found in the hearts of mice in other groups. Brain natriuretic peptide was significantly increased in groups B and D, and C-reactive protein was significantly increased in each group. Conclusion Our research finally found that the HFrEF mice model created by injection at a dose of 100 mg/kg for 7 days was the most suitable and a relatively stable chronic heart failure model could be obtained by placing it for 21 days.

AKAP12 Upregulation Associates With PDE8A to Accelerate Cardiac Dysfunction

“…In the WT groups, we noticed that the Ejection Fraction % (EF%) and Fractional Shortening % (FS%) showed divergent responses after 14 days of treatment with 60 mg/kg per day of ISO; where some mice exhibited an increase in EF% and FS% while others experienced a decrease, aligning with prior findings with variable ISO doses. 22–24 However, all male and female AKAP12 OX mice demonstrated reduced EF% and FS% after the 14-day treatment period (Figure 7A, 7B, 7E, and 7F).…”

“…In the WT groups, we noticed that the Ejection Fraction % (EF%) and Fractional Shortening % (FS%) showed divergent responses after 14 days of treatment with 60 mg/kg per day of ISO; where some mice exhibited an increase in EF% and FS% while others experienced a decrease, aligning with prior findings with variable ISO doses. [22][23][24] However, all male and female AKAP12 OX mice demonstrated reduced EF% and FS% after the 14-day treatment period (Figure 7A, 7B, 7E, and 7F). Precisely, both male and female AKAP12 OX mice had significantly lower EF% (42.97±5.78% and 43.89±3.61%) as compared with WT littermates post-ISO treatment (65.22±4.07% and 57.39±3.95%; P=9.9×10 −3 and P=3.5×10 −2 ), respectively.…”

Transcriptional changes during isoproterenol-induced cardiac fibrosis in mice

“…Isoproterenol is a well-studied β-adrenergic agonist that activates the β1 adrenergic receptors in the heart, leading to cardiac hypertrophy, which progresses gradually toward fibrosis and heart failure ( Park et al, 2018 ; He et al, 2019 ). A moderate dose of isoproterenol (4–60 mg/kg/day) can induce cardiac hypertrophy and fibrosis ( Oudit et al, 2003 ; Park et al, 2018 ; Grant et al, 2020 ; Pan et al, 2022 ) in 7–15 days; the TAC model takes approximately 4–8 weeks to develop fibrosis ( Li et al, 2022 ). Although TAC is an excellent model that very closely mimics pathological conditions like aortic stenosis, isoproterenol serves as an alternative and quick method to develop fibrosis.…”