Abstract 18923: S-Nitroso Human Serum Albumin versus Inhaled Nitric Oxide for the Treatment of Pulmonary Hypertension in a Chronic Right Ventricle Volume Overload Model

Abstract

Background: The study aimed to compare the acute overall hemodynamic and oxidative stress effects of intravenous S-NO-human serum albumin (S-NO-HSA) infusion and inhaled nitric oxide (iNO) in a chronic left-to-right shunt-induced pulmonary arterial hypertension model. Methods and Results: Male Wistar rats underwent surgical creation of aorto-caval fistula (Qp/Qs> 2.0). After 10 weeks they were randomly treated with human serum albumin (HSA) (controls; n. 25), S-NO-HSA (0.5 μmol/kg/h; n. 30) or iNO (20 ppm; n. 35) for 60 minutes. Right ventricular contractility, right ventricular-vascular coupling and ventricular interdependence were assessed in vivo at different preloads by biventricular conductance catheters prior and after 60 minutes treatment. Heart and lung biopsies were obtained to determine oxidative stress by oxidized to reduced glutathione (GSSG/GSH) ratio and high-energy phosphates content. Both S-NO-HSA and iNO led to a significant reduction in right ventricular afterload expressed by effective pulmonary arterial elastance (Ea) (from 1.3 ±0.2 to 0.5 ±0.3 and 0.4 ±0.2 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 a significant increase in the efficiency of ventricular-vascular coupling (Ees/Ea) occurred after S-NO-HSA but not iNO treatment (from 0.33 ±0.15 to 0.98 ±0.21; P< 0.005 and from 0.35 ±0.16 to 0.45 ±0.18; P< 0.1 respectively) with significant increase in left ventricular stroke volume (58 ±7 vs 18 ± 9 %; P< 0.003). S-NO-HSA compared to iNO improved right ventricle phosphocreatine content (27.08 ±11.35 vs. 8.41 ±1.80 nmol/mg protein; P<0.001) and myocardial energy charge (0.85 ±0.03 vs. 0.78 ±0.03; P<0.01). Both S-NO-HSA and iNO decreased lung and right ventricular GSSG/GSH ratio (P<0.001). CONCLUSIONS: S-NO-HSA is more effective than iNO in treating pulmonary hypertension, improving right ventricle diastolic function and right ventricular-arterial coupling with a positive effect on ventricular interdependence. This results in superior energetic reserve of the heart, despite similar reduction of lung and right ventricular oxidative stress.