Abstract 14354: Cardiorenal Actions of the Designer Natriuretic Peptide, Cenderitide, in a Severe Heart Failure Model Treated With Furosemide Bolus
BACKGROUND: Diuretic therapy can provide symptomatic improvement in congestive heart failure (HF) although diuretic resistance and renal dysfunction can occur. Cenderitide (or CD-NP, “CD”), now in clinical trials for acute HF, is a Mayo designed chimeric natriuretic peptide which, unlike the native natriuretic peptides (NPs) ANP, BNP and CNP, binds both to guanylyl cyclase (GC)-B and GC-A with greatest affinity for GC-B. CD was designed to mediate more venodilation than arterial dilation via GC-B and so result in less hypotension than BNP or ANP, but also possess natriuretic and diuretic properties via GC-A activation. We hypothesized that combining CD with furosemide (“F”) will increase natriuresis compared to F alone without causing excessive hypotension or renal dysfunction.
METHODS: HF was induced in 2 groups of dogs by tachypacing at 240 bpm. On day 11 of pacing an acute study was performed under general anesthesia. The renal artery was equipped with an electromagnetic flow probe. Inulin was infused to measure GFR. After equilibration a 30' baseline clearance (C1) was done. After that, one group (F+CD; n=3) received a F bolus (1 mg/kg) and a 105' CD infusion (100 ng/kg/min). After a 15' lead-in, three 30' clearances were done (C2, C3, C4). The other group (F; n=4) received the F bolus plus vehicle. Changes from baseline were compared between groups by unpaired t-test. Values are mean±SEM. *p<0.05 between groups.
RESULTS: F+CD compared to F resulted in greater increases in sodium excretion* in C4 (+330±50 vs +141±49 µEq/min) and this tended to be the case in C3 (p=0.07). Renal blood flow tended to be higher with F+CD in C4 (+58±15 vs +12±11 mL/min, p=0.058). Compared to F, F+CD reduced right atrial pressure (* for C2-C4), pulmonary artery pressure (C4*), and pulmonary vascular resistance (C4*) but did not result in systemic hypotension.
CONCLUSION: The combination of bolus furosemide+cenderitide significantly increased natriuresis as compared to furosemide alone. Also, compared to F alone, F+CD reduced right atrial pressure and pulmonary vascular resistance more, without inducing systemic hypotension. These promising findings suggest that adding cendiritide to furosemide may enhance renal response to diuretics with additional preload reduction in HF.
- © 2011 by American Heart Association, Inc.