Abstract 13335: Impaired B-type Natriuretic Peptide Effets on Neutrophil Burst in Heart Failure Patients
Purpose: The cardiac natriuretic peptide system is activated in heart failure (HF); however, B-type natriuretic peptide (BNP)-based restoration of homeostasis is inadequate. The equivocal clinical benefit associated with administration of a recombinant BNP, nesiritide, raises the possibility of BNP resistance in HF patients. We therefore tested the hypothesis that BNP effect on neutrophil burst is impaired in patients with HF.
Methods: HF patients admitted to hospital were studied both at acute presentation and after 3 weeks’ therapy. Neutrophils were isolated with a Ficoll gradient technique followed by lysis of red blood cells and resuspend in Hank’s Balanced Salt Solution with purity of >95% and viability of >98%. Neutrophils were pre-incubated with BNP (1nM and 1uM); superoxide (O2-) generation in response to N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) (1uM) and phorbol 12-myristate 13-acetate (PMA) (100nM) was quantitated by EPR spectroscopy.
Results: BNP (1uM) inhibited both fMLP- and PMA-associated O2- production in normal subjects (n=20) by [29±5%] and [38±7%] respectively ([[Unable to Display Character: ★]]P<0.0001 for both; Figure A); This effect does not vary with age. In acute HF patients, there was significant attenuation of BNP effects vs normal subjects for both PMA- and fMLP-induced O2- release ([[Unable to Display Character: ★]][[Unable to Display Character: ★]]p<0.05; Figure B&C). At three weeks’ follow-up of HF patients, BNP effect on neutrophil O2- release does not consistently improve (Figure D). The mediation of this effect by O2- release was confirmed via its total inhibition by diphenyleneiodonium.
Conclusions: 1. BNP acts as a suppressor of O2- release from neutrophils.
2. This effect is lost in patients with acute heart failure, thus confirming resistance to this action of BNP.
3. It remains uncertain whether successful treatment of HF restores tissue response to BNP.
- © 2013 by American Heart Association, Inc.