Abstract 17638: Systemic Cardiovascular Effects of Intravenous Urocortin 2 and Urocortin 3 in Patients with Heart Failure and Healthy Volunteers

Abstract

Introduction: Urocortin 2 (UCN 2) and urocortin 3 (UCN 3) are endogenous peptide hormones with an emerging role in the pathophysiology and treatment of heart failure. For the first time, we examined the systemic cardiovascular effects of both UCN 2 and UCN 3 in healthy volunteers and patients with heart failure. Methods: Seven healthy volunteers (Group A) and nine patients with stable chronic heart failure (Group B, New York Heart Association class II and III, left ventricular ejection fraction <35%) on optimal medical therapy underwent non-invasive oscillometric sphygmomanometry and impedance cardiography during incremental intravenous infusions of sodium nitroprusside (0.15/0.5/1.5 μg/kg/min), UCN 2 (0.16/0.48/1.6 μg/min), UCN 3 (5/15/50 μg/min) and saline placebo in a randomised double blind two-way cross over study. Results: Other than diastolic blood pressure (78 vs 72 mmHg for Group A and B respectively, p<0.05), haemodynamic variables were similar at baseline of each infusion and were unchanged by saline placebo infusion (p>0.05 for all). SNP, UCN2 and UCN 3 infusions increased heart rate and cardiac index, and reduced systolic and diastolic blood pressure and peripheral vascular resistance index (PVRI) in both healthy volunteers and patients with heart failure (p<0.05 for all; see Figure 1). There were no significant differences in the changes in cardiac index or PVRI between healthy volunteers and patients with heart failure during either UCN 2 or UCN 3 infusions (p>0.05). Conclusion: Intravenous UCN 2 and especially UCN 3 increase cardiac output and reduce peripheral vascular resistance. This favourable haemodynamic profile suggests that UCN 2 and UCN 3 hold exciting therapeutic potential for the treatment of acute heart failure.