Abstract 15421: Acute Intravenous Infusion of Human Stresscopin (JNJ-39588146) Improves Left Ventricular Systolic Performance in Dogs with Advanced Heart Failure
Background: JNJ-39588146/human Stresscopin (STC) is a newly identified peptide member of the corticotropin-releasing factor (CRF) family that binds selectively and with high affinity to the CRF type 2 receptor (CRFR2). This study examined the acute effects of intravenous administration of STC on left ventricular (LV) systolic function in dogs with advanced heart failure (HF).
Methods: Studies were performed in 6 anesthetized dogs with intracoronary microembolization-induced HF. LV pressure-volume (P-V) loops were generated using a Millar Instruments MPVS Ultra system in conjunction with a pressure-conductance catheter positioned within the LV cavity. Loops were recorded during transient balloon occlusion of the inferior Vena Cava and used to assess the slope of the LV end-systolic pressure volume relationship (ESPVR) and LV end-diastolic pressure-volume relationship (EDPVR). Hemodynamic, ventriculographic and PV-loop measurements were made before and 2 hours into intravenously administration of STC at a dose of 4.3ng/kg/min.
Results: Compared to baseline, administration of STC significantly increased LV ejection fraction, cardiac output and the slope of the ESPVR while only modestly decreasing the slope of the EDPVR. These improvements in LV systolic function occurred without a significant increase of heart rate (HR) or a decrease of mean aortic blood pressure (mAoP) and without eliciting de-novo ventricular arrhythmias.
Conclusions: In dogs with advanced HF, acute intravenous administration of STC increased LV contractile performance significantly without changing HR, or mAoP and without eliciting de-novo ventricular arrhythmias. These findings support the continued development of STC for the treatment of patients with acute HF syndromes.
- © 2012 by American Heart Association, Inc.