Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Rungatscher, A; Hallström, S; Linardi, D; Milani, E; Gasser, H; Podesser, BK; Scarabelli, TM; Luciani, GB; Faggian, G.
S-nitroso human serum albumin attenuates pulmonary hypertension, improves right ventricular-arterial coupling, and reduces oxidative stress in a chronic right ventricle volume overload model.
J Heart Lung Transplant. 2015; 34(3):479-488
Doi: 10.1016/j.healun.2014.09.041
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Hallström Seth
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- Abstract:
- This study examined the acute effect of intravenous S-nitroso human serum albumin (S-NO-HSA) infusion on overall hemodynamics and oxidative stress in a chronic left-to-right shunt-induced pulmonary arterial hypertension model with right ventricle (RV) failure. An aortocaval fistula (pulmonary-to-systemic blood flow ratio [Qp/Qs] > 2.0) was surgically created in 50 male Wistar rats. After 10 weeks, they were randomly treated with S-NO-HSA (n = 20) or human serum albumin (HSA; n = 25) infusion (0.5 µmol/kg/h) for 60 minutes. A sham group (n = 10) received S-NO-HSA. RV contractility, RV-vascular coupling, and ventricular interdependence were assessed in vivo at different pre-loads by biventricular conductance catheters. Heart and lung biopsy specimens were obtained for determination of high-energy phosphates, oxidative stress (oxidized glutathione/reduced glutathione), and endothelial nitric oxide synthase protein expression. S-NO-HSA, compared with HSA infusion, reduced RV afterload expressed by effective pulmonary arterial elastance (Ea; 0.49 ± 0.3 vs 1.2 ± 0.2 mm Hg/ml; p = 0.0005) and improved RV diastolic function (slope of end-diastolic pressure-volume relationship) as well as contractility indicated by slope of end-systolic pressure-volume relationship (Ees). Therefore an increase in efficiency of ventricular-vascular coupling (Ees/Ea) occurred after S-NO-HSA (0.35 ± 0.17 to 0.94 ± 0.21; p = 0.005), but not HSA infusion, leading to positive effect on ventricular interdependence with increased left ventricular stroke volume (56% ± 4% vs 19% ± 5%; p = 0.0013). S-NO-HSA, compared with HSA, treatment improved adenosine 5'-triphosphate (13.9 ± 1.1 vs 7.0 ± 1.8 µmol/g protein) and phosphocreatine (5.9 ± 3.3 vs 1.9 ± 0.6 µmol/g protein; p = 0.01) RV content and decreased the tissue oxidized glutathione/reduced glutathione ratio (p = 0.001). S-NO-HSA reduces pulmonary hypertension and improves RV systolic and diastolic function and RV-arterial coupling, with a positive effect on ventricular interdependence by increasing energetic reserve and reducing oxidative stress. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Blotting, Western -
- Chronic Disease -
- Disease Models, Animal -
- Heart Ventricles - metabolism
- Heart Ventricles - physiopathology
- Humans -
- Hypertension, Pulmonary - complications
- Hypertension, Pulmonary - metabolism
- Hypertension, Pulmonary - physiopathology
- Male -
- Nitroso Compounds - blood
- Oxidative Stress -
- Rats -
- Rats, Wistar -
- Serum Albumin -
- Serum Albumin, Human -
- Ventricular Dysfunction, Right - etiology
- Ventricular Dysfunction, Right - metabolism
- Ventricular Dysfunction, Right - physiopathology
- Ventricular Function, Right -
- Find related publications in this database (Keywords)
- pulmonary hypertension
- right ventricle
- pressure-volume
- ventricular-arterial coupling
- oxidative stress
- high-energy phosphates
- S-nitroso human serum albumin
- animal model