Michael S. Sabbah

Effects of acute intravenous infusion of apelin on left ventricular function in dogs with advanced heart failure.

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.

LONG-TERM THERAPY WITH ROSUVASTATIN INCREASES PROTEIN EXPRESSION OF GROWTH FACTORS AND STEM CELL MARKERS IN LEFT VENTRICULAR MYOCARDIUM OF DOGS WITH MODERATE HEART FAILURE

Background: HMG-CoA reductase inhibitors or “statins” lower LDL and reduce mortality from coronary disease. Statins also possess other pleiotropic effects. We showed that therapy with rosuvastatin (RSV) in dogs with moderate heart failure (HF) prevents progressive LV dysfunction and dilation. This study examined the effects of RSV on protein expression of key stem cell (SC) markers cKit and Sca1 and vascular (VEGF) and fibroblast (FGF)growth factors in dogs with microembolization-induced HF.