Abstract
BACKGROUND: Apelin-13 (APLN) through apelin receptor (APJ) exerts peripheral vasodilatory and potent positive inotropic effects. We examined the effects of exogenous intravenous infusion of APLN on left ventricular (LV) systolic function in dogs with heart failure (HF, LV ejection fraction, EF~30%). METHODS AND RESULTS: Studies were performed in 7 dogs with microembolization-induced HF. Each dog received an intravenous infusion of low dose and high dose APLN followed by washout period. LV end-diastolic volume (EDV), end-systolic volume (ESV) and LV EF were measured at specified time points. APLN protein level was determined in plasma at all time points. mRNA and protein levels of APLN and APJ in LV tissue were also measured in 7 normal (NL) and 7 heart failure (HF) dogs. APLN reduced EDV only at the high dose, significantly reduced ESV and increased EF with both doses. In plasma of HF dogs, APLN levels were reduced significantly compared to NL dogs. APLN treatment in HF dogs significantly increased the plasma APLN levels at both low and high doses. Expression of APLN, but not of APJ, was reduced in LV tissue of HF dogs compared to NL. CONCLUSIONS: Exogenous administration of APLN improved LV systolic function in dogs with advanced HF.