Abstract 12198: Effect of Repeat Intravenous Infusion of Vepoloxamer (Purified Sodium-Free Poloxamer 188) on Left Ventricular Systolic Function in Dogs With Advanced Heart Failure
Introduction: Ca2+ overload occurs in heart failure (HF) leading to cardiomyocyte dysfunction and death. Vepoloxamer (VEPO), purified sodium-free poloxamer 188, is a rheologic agent that, in HF, has been suggested to improve microvascular blood flow and repair damaged cell membranes, possibly inhibiting unregulated Ca2+ entry into cardiomyocytes. We examined the effects of repeat acute i.v. infusion of VEPO on LV function in dogs with microembolization-induced HF (LV ejection fraction, EF~30%).
Methods: 14 HF dogs were randomized to 2 hours infusions of VEPO (450 mg/kg, n=7) or v/v normal saline (control, n=7). Each dog received 2 infusions of VEPO or saline 3 weeks apart. Dogs were followed for an additional 3 weeks after the 2nd infusion (total follow-up 6 weeks). LV end-diastolic (EDV) and end-systolic (ESV) volumes, EF, and plasma n-terminal-pro brain natriuretic peptide (nt-pro BNP) were measured at baseline, at end infusion 1st infusion, and at 24 hours, 1, 2 and 3 weeks thereafter and then again at 24 hours, 1, 2 and 3 weeks after the 2nd infusion. The change between baseline and other time points (treatment effect, Δ) was calculated.
Results: Data are shown in the table. Saline had no effect on any measures. Compared to saline control, VEPO reduced ESV and nt-pro BNP and increased EF without affecting EDV, heart rate or aortic pressure. The benefits were sustained for up to at least 2 weeks after the 1st VEPO dose and up to 3 weeks after the 2nd dose.
Conclusions: Therapy with multiple intravenous 2 hours infusions of VEPO, pulsed at 3 week intervals, elicit progressively sustained improvement in LV systolic function evident for at least 6 weeks. The results support development of MST-188 for the treatment of acute HF and potentially for continued therapy post-hospital discharge.
Author Disclosures: H.N. Sabbah: Consultant/Advisory Board; Modest; Stealth Biotherapeutics, Inc., Mast Therapeutics, Inc.. Research Grant; Significant; Stealth Biotherapeutics, Inc., Mast Therapeutics, Inc.. M. Wang: None. K. Zhang: None. R.C. Gupta: None. M. Emanuele: Employment; Significant; Mast Therapeutics, Inc..
- © 2015 by American Heart Association, Inc.