Abstract 15385: Acute Intravenous Infusion of Bendavia (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular Systolic Function in Dogs with Advanced Heart Failure

Background: Bendavia (MTP-131) is a novel mitochondria-targeting peptide that improves the efficiency of mitochondria electron transfer chain and improves mitochondria respiration and ATP synthesis. This study examined the acute effects of intravenous Bendavia on left ventricular (LV) systolic function in dogs with advanced heart failure (HF). Methods: Studies were performed in 12 anesthetized dogs with intracoronary microembolization-induced HF. Seven dogs, selected at random, received intravenous Bendavia at a dose of 0.05 mg/kg/hr for 2 hours and 5 dogs received a volume matched placebo control (normal saline) also administered over 2 hours. Hemodynamic and ventriculographic measurements were made at baseline, prior to drug administration, and at the end of 2 hours of drug or placebo infusion. Measurements included heart rate (HR), mean aortic pressure (mAoP), LV ejection fraction (EF), stroke volume (SV), cardiac output (CO), LV peak +dP/dt and systemic vascular resistance (SVR). Results: Data are shown in the table (mean ± SEM). Compared to baseline, saline infusion over 2 hours had no effect on HR, mAoP, EF, ESV, SV, peak +dP/dt and SVR. Infusion of Bendavia also had no effect on HR, mAoP or SVR but significantly increased EF, SV, CO and +dP/dt. Conclusions: In dogs with advanced HF, acute intravenous administration of Bendavia improved LV systolic function without increasing heart rate or decreasing systemic pressure and SVR. The improvement of LV function is likely the result of improved cardiac energetics. The findings support the continued development of Bendavia for the treatment of patients with acute HF syndromes.