Abstract 17487: S-Nitroso Human Serum Albumin (S-NO-HSA) Attenuates Pulmonary Hypertension, Improves Right Ventricular-Arterial Coupling and Reduces Oxidative Stress in a Chronic Right Ventricle Volume Overload Model

Abstract

BACKGROUND The study was aimed to examine the acute overall hemodynamic and oxidative stress effects to intravenous S-NO-HSA infusion in a model of chronic left-to-right shunt-induced pulmonary arterial hypertension and right ventricle failure. METHODS AND RESULTS Fifty male Wistar rats underwent surgical creation of aorto-caval fistula (Qp/Qs> 2.0) After 10 weeks they were randomly treated with S-NO-HSA (0.5 υmol/kg/h) (n. 20) or human serum albumin (HSA) (n. 25) infusion for 60 minutes. Right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence were assessed in vivo ad different preloads by biventricular conductance catheters prior and after 60 minutes infusion. Heart and lung biopsies were obtained to determine oxidative stress by reduced to oxidized glutathione (GSH/GSSG) ratio and high energy phosphates content. S-NO-HSA compared to HSA infusion resulted in a significant reduction in right ventricular afterload expressed by effective pulmonary arterial elastance (Ea) (0.49 +/- 0.3 versus 1.2 +/- 0.2 mmHg/ml; P = 0.0005). S-NO-HSA significantly improve right ventricular diastolic function (slope of end-diastolic pressure-volume relations) but not contractility (slope of preload recruitable stroke work), whereas a significant increase in the efficiency of ventricular-vascular coupling (ratio of end-systolic to pulmonary arterial elastances: Ees/Ea) occurred after S-NO-HSA but not HSA infusion (from 0.35 +/- 0.17 to 0.94 +/- 0.21; P = 0.005 and from 0.37 +/- 0.11 to 0.43 +/- 0.19; P = 0.1 respectively) with significant increase in left ventricular stroke volume (56 +/- 4 vs 9 +/- 5 %; P = 0.0013). S-NO-HSA compared to HSA treatment significantly improved ATP and PCr right ventricle myocardial content (13.9 +/- 1.1 vs. 7.0 +/- 1.8 and 5.9 +/- 3.3 vs. 1.9 +/- 0.6 micromol/g protein; P = 0.01) and increase tissue GSH/GSSG ratio (P = 0.001). CONCLUSIONS: S-NO-HSA reduces pulmonary hypertension and improves right ventricular diastolic function and right ventricular-arterial coupling with a positive effect on ventricular interdependence. This results in an increased energetic reserve of the heart and reduction of oxidative stress.