BACKGROUNDThe study aimed to compare the acute overall hemodynamic and oxidative stress effects of intravenous S-NO-human serumalbumin (S-NO-HSA) infusion and inhaled nitric oxide (iNO) in a chronic left-to-right shunt-induced pulmonary arterialhypertension model.METHODS AND RESULTSMale Wistar rats underwent surgical creation of aorto-caval fistula (Qp/Qs> 2.0). After 10 weeks they were randomly treatedwith 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 atdifferent preloads by biventricular conductance catheters prior and after 60 minutes treatment. Heart and lung biopsies wereobtained to determine oxidative stress by oxidized to reduced glutathione (GSSG/GSH) ratio and high-energy phosphatescontent.Both S-NO-HSA and iNO led to a significant reduction in right ventricular afterload expressed by effective pulmonary arterialelastance (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 rightventricle 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 butnot 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) withsignificant 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 andright 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 rightventricular-arterial coupling with a positive effect on ventricular interdependence. This results in superior energetic reserve ofthe heart, despite similar reduction of lung and right ventricular oxidative stress.
S-Nitroso Human Serum Albumin Versus Inhaled Nitric Oxide for the Treatment of Pulmonary Hypertension in a Chronic Right Ventricle Volume Overload Model.
RUNGATSCHER, Alessio;LUCIANI, GIOVANNI BATTISTA;FAGGIAN, Giuseppe
2013-01-01
Abstract
BACKGROUNDThe study aimed to compare the acute overall hemodynamic and oxidative stress effects of intravenous S-NO-human serumalbumin (S-NO-HSA) infusion and inhaled nitric oxide (iNO) in a chronic left-to-right shunt-induced pulmonary arterialhypertension model.METHODS AND RESULTSMale Wistar rats underwent surgical creation of aorto-caval fistula (Qp/Qs> 2.0). After 10 weeks they were randomly treatedwith 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 atdifferent preloads by biventricular conductance catheters prior and after 60 minutes treatment. Heart and lung biopsies wereobtained to determine oxidative stress by oxidized to reduced glutathione (GSSG/GSH) ratio and high-energy phosphatescontent.Both S-NO-HSA and iNO led to a significant reduction in right ventricular afterload expressed by effective pulmonary arterialelastance (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 rightventricle 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 butnot 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) withsignificant 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 andright 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 rightventricular-arterial coupling with a positive effect on ventricular interdependence. This results in superior energetic reserve ofthe heart, despite similar reduction of lung and right ventricular oxidative stress.
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