Abstract 16763: Mechanical Circulatory Support Promotes Myocardial Nitric Oxide Signaling in Heart Failure Patients
Introduction: The integrity of the cardiovascular system is dependent on the continuous generation of nitric oxide (NO). Reduction in NO bioavailability is central to the development of cardiovascular disorders and patients with heart failure (HF) exhibit blunted endothelium-dependent flow-mediated dilation in indicating diminished NO release. We have previously reported that patients with heart failure have marked reductions in circulating NO metabolites and that NO-based therapies significantly reverse left ventricular (LV) dysfunction in preclinical animal models of HF.
Methods: Plasma and left ventricular (LV) tissue were collected in HF patients (n=10) at the time of left ventricular assist device (LVAD) implantation. Plasma and LV tissue were again collected in the same 10 patients at the time of cardiac transplantation. Plasma and cardiac nitrite concentrations were determined by ion chromatography methods and nitrosylated protein (RXNO) levels were measured by chemiluminescence detection. Cyclic guanosine 5’-monophosphate (cGMP) was analyzed using radioimmunoassay technique.
Results: Results: Following LVAD implantation, RXNO (NO-bound protein) levels were significantly elevated in both circulation and in the LV (10.2 nM vs. 33.3 nM, p < 0.05). Downstream NO signaling activates soluble guanylyl cyclase to form cGMP. Interestingly, LV cGMP levels were significantly augmented post-LVAD implantation (p<0.01). In contrast, plasma and cardiac nitrite (NO2) levels remained unchanged.
Conclusions: These data strongly suggest that cardiovascular remodeling accompanying LVAD implantation promotes endothelial nitric oxide synthase (eNOS) function and increases NO bioavailability and signaling.
Author Disclosures: D.J. Polhemus: None. Y. Tao: None. S.C. Koenig: None. S.D. Prabhu: Research Grant; Significant; NIH and VA grants. D. Lefer: None.
- © 2014 by American Heart Association, Inc.