Abstract 20867: Prolonged Treatment With S-Nitroso Human Serum Albumin Compared to Inhaled Nitric Oxide is More Effective and Prevents Inflammatory and Oxidative Effects in Experimental Pulmonary Arterial Hypertension
Introduction: Inhaled nitric oxide (iNO) is approved for use in persistent pulmonary hypertension of the newborn but its toxicological effects including lung inflammation and oxidative damage are well known. We have previously reported that intravenous S-NO-HSA has superior hemodynamic effects than iNO in pulmonary hypertension.
Hypothesis: The present study aimed to compare the chronic overall hemodynamic, inflammatory and oxidative stress effects of intravenous S-NO-HSA infusion and iNO in a chronic left-to-right shunt-induced pulmonary arterial hypertension model.
Methods and Results: Rats with chronic exposure to left-to-right shunt by surgical creation of aorto-caval fistula (Qp/Qs> 2.0) developed pulmonary arterial hypertension. After 20 weeks they were randomly treated with iNO (20 ppm; n=30) or S-NO-HSA (0.2 μmol/kg/h; n=30) for 24 hours. Both S-NO-HSA and iNO led to a significant reduction in right ventricular afterload expressed by effective pulmonary arterial elastance (Ea) (from 1.4 ±0.2 to 0.6 ±0.2 and 0.4 ±0.1 respectively; P< 0.001). Only S-NO-HSA significantly improved right ventricle diastolic function (slope of end-diastolic pressure-volume relation) and contractility indicated by end-systolic elastance (Ees). Therefore significant increase in the efficiency of ventricular-vascular coupling (Ees/Ea) occurred after S-NO-HSA but not iNO treatment. S-NO-HSA compared to iNO improved right ventricle phosphocreatine content and myocardial energy charge. Nitrotyrosine (marker of peroxynitrite-mediated reactions), TNF- α, IL-1, expression of nitric oxide synthases 2 and apoptosis were increased in right ventricle and lung tissue in rats treated with iNO but not S-NO-HSA. Furthemore lung wet/dry ratio was higher in iNO treated rats with higher degree of perivascular inflammation.
Conclusions: Prolonged treatment with S-NO-HSA is more effective than iNO in pulmonary hypertension with improvement in right ventricle diastolic and systolic function, right ventricular-arterial coupling as well as positive effect on energetic myocardial reserve. Moreover S-NO-HSA does not produce inflammatory and oxidative effects caused by iNO.
Author Disclosures: A. Rungatscher: None. S. Hallström: None. D. Linardi: None. C. Rossmann: None. N. Ahmed: None. F. Merigo: None. G. Luciani: None. G. Faggian: None.
- © 2016 by American Heart Association, Inc.