Background Elamipretide (MTP-131), a novel mitochondria-targeting peptide, was shown to reduce infarct size in animals with myocardial infarction and improve renal function in pigs with acute and chronic kidney injury. This study examined the effects of chronic therapy with elamipretide on left ventricular (LV) and mitochondrial (MITO) function in dogs with heart failure (HF). Methods and Results 14 dogs with microembolization-induced HF were randomized to 3 months monotherapy with subcutaneous injections of elamipretide (0.5 mg/kg once daily, HF+ELA, n=7) or saline (Control, HF-CON, n=7). LV ejection fraction (EF), plasma n-terminal pro-brain natriuretic peptide (nt-pro BNP), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) were measured before (pre-treatment) and 3 months after initiating therapy (post-treatment). MITO respiration, membrane potential (Δψm), maximum rate of ATP synthesis and ATP/ADP ratio were measured in isolated LV cardiomyocytes obtained at post-treatment. In HF-CON dogs, EF decreased at post-treatment compared to pre-treatment (29±1% vs. 31±2%); whereas in HF+ELA dogs, EF significantly increased at post-treatment compared to pre-treatment (36±2% vs. 30±2%, p<0.05). In HF-CON, nt-pro BNP increased by 88±120 pg/ml during follow-up but decreased significantly by 774±85 pg/ml in HF+ELA dogs (p<0.001). Treatment with elamipretide also normalized plasma TNF-α and CRP and restored MITO state-3 respiration, Δψm, rate of ATP synthesis and ATP/ADP ratio (ATP/ADP: 0.38±0.04 HF-CON vs. 1.16±0.15 HF+ELA, p<0.001). Conclusions Long-term therapy with elamipretide improves LV systolic function, normalizes plasma biomarkers and reverses MITO abnormalities in LV myocardium of dogs with advanced HF. The results support the development of elamipretide for the treatment of HF.

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose The American Society of Health-System Pharmacists (ASHP) and Pediatric Pharmacy Advocacy Group (PPAG) guidelines for providing pediatric pharmacy services in hospitals and health systems can be used to improve medication safety wherever pediatric patients receive care, including in the emergency department (ED). The purpose of this initiative was to improve compliance with these guidelines in a primarily adult ED. Methods This quality improvement initiative was conducted in a level 1 trauma center ED between October 2019 and March 2020. The ASHP-PPAG guidelines were used to create practice elements applicable to the ED. An initial compliance assessment defined elements as noncompliant, partially compliant, fully compliant, or not applicable. Investigators identified interventions to improve compliance for noncompliant or partially compliant elements and then reassessed compliance following implementation. Data were expressed using descriptive statistics. This initiative was exempt from institutional review board approval. Results Ninety-three ED practice elements were identified within the 9 standards of the ASHP-PPAG guidelines. At the initial compliance assessment, the majority (59.8%) of practice elements were fully compliant; however, various service gaps were identified in 8 of the standards, and 16 interventions were implemented to improve compliance. At the final compliance assessment, there was a 19.5% increase in full compliance. Barriers to achieving full compliance included technology restrictions, time constraints, financial limitations, and influences external to pharmacy. Conclusion This quality improvement initiative demonstrated that the ASHP-PPAG guidelines can be used to improve ED pediatric pharmacy services in a primarily adult institution. The initiative may serve as an example for other hospitals to improve compliance with the guidelines.