Abstract Body: Objective: To determine whether ARA290 can prevent or delay age-related declines in cardiac function and structure in the TG^AC8 heart failure model.
Methods: The study consists of 9 TG^{AC8 +} mice that were randomly assigned to treatment group (n=5) or non-treatment saline group (n=4). Both groups received intraperitoneal injections of ARA290 (100 μg/kg) or saline tri-weekly. Monthly echocardiographic assessment of heart systolic function prior to, and monthly during 7 months of treatment was performed starting at 10 months of age. Two Way ANOVA was used to analyze the data.
Results: At baseline, 10 months of age, prospective treatment and non-treatment group did not exhibit any statistically significant difference in their measure of ejection fraction (EF), fractional shortening (FS), and stroke volume (SV) (P > 0.05).
ARA290 treatment preserved EF, FS, and SV, (compared to a progressive, time dependent deterioration of these systolic functions in the saline treated group). Significant interaction terms for EF (P < 0.04), FS (P < 0.03), and SV (P < 0.02), and time indicated that the ARA290 effect depended upon treatment time.
Conclusion:
The prevention of the decline in heart systolic functional by ARA290 suggests that this small peptide derivative of EPO has therapeutic potential as a novel intervention to retard declines in cardiac function that accompany chronic heart diseases.