Vepoloxamer (VEPO), a rheologic agent, repairs damaged cell membranes, thus inhibiting unregulated Ca entry into cardiomyocytes. This study examined the effects of i.v. infusion of VEPO on LV function in dogs with coronary microembolization-induced heart failure (HF) (LV ejection fraction, EF ~ 30%).
Thirty-five HF dogs were studied. Study 1: 21 of 35 dogs were randomized to 2-h infusion of VEPO at dose of 450 mg/kg (n = 7) or VEPO at 225 mg/kg (n = 7) or normal saline (control, n = 7). Hemodynamics were measured at 2 h, 24 h, 1 week, and 2 weeks after infusion. Study 2: 14 HF dogs were randomized to 2-h infusions of VEPO (450 mg/kg, n = 7) or normal saline (control, n = 7). Each dog received 2 infusions of VEPO or saline (pulsed therapy) 3 weeks apart and hemodynamics measured at 24 h, and 1, 2, and 3 weeks after each infusion. In both studies, the change between pre-infusion measures and measures at other time points (treatment effect, Δ) was calculated.
Study 1: compared to pre-infusion, high dose VEPO increased LVEF by 11 ± 2% at 2 h, 8 ± 2% at 24 h (p < 0.05), 8 ± 2% at 1 week (p < 0.05), and 4 ± 2% at 2 weeks. LV EF also increased with low-dose VEPO but not with saline. Study 2: VEPO but not saline significantly increased LVEF by 6.0 ± 0.7% at 2 h (p < 0.05); 7.0 ± 0.7%% at 1 week (p < 0.05); 1.0 ± 0.6% at 3 weeks; 6.0 ± 1.3% at 4 weeks (p < 0.05); and 5.9 ± 1.3% at 6 weeks (p < 0.05).
Intravenous VEPO improves LV function for at least 1 week after infusion. The benefits can be extended with pulsed VEPO therapy. The results support development of VEPO for treating patients with acute on chronic HF.