S-Nitroso Human Serum Albumin Versus Inhaled Nitric Oxide for the Treatment of Pulmonary Hypertension in a Chronic Right Ventricle Volume Overload Model.

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 \u3bcmol/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 \ub10.2 to 0.5 \ub10.3 and 0.4 \ub10.2 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 \ub10.15 to 0.98 \ub10.21; P< 0.005 and from 0.35 \ub10.16 to 0.45 \ub10.18; P< 0.1 respectively) withsignificant increase in left ventricular stroke volume (58 \ub17 vs 18 \ub1 9 %; P< 0.003).S-NO-HSA compared to iNO improved right ventricle phosphocreatine content (27.08 \ub111.35 vs. 8.41 \ub11.80 nmol/mg protein;P<0.001) and myocardial energy charge (0.85 \ub10.03 vs. 0.78 \ub10.03; 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

Cardioprotective Effects of S-Nitroso Human Serum Albumin (S-NO-HSA) during Cardioplegic Arrest and Cold Storage in a Working Heart Heterotopic Transplant Model

Cardioprotective Effects of S-Nitroso Human Serum Albumin (S-NO-HSA) during Cardioplegic Arrest and Cold Storage in a Working Heart Heterotopic Transplant Mode

S-Nitroso Human Serum Albumin Versus Inhaled Nitric Oxide for the treatment of pulmonary hypertension in a chronic right ventricle volume overload model.

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

Pharmacologically induced hypothermia with cannabinoid receptor agonist WIN55,212-2 vs mild therapeutic hypothermia in a rat model of cardiac arrest with extracorporeal life support.

To compare the hemodynamic, cardioprotective and metabolic effects of cannabinoid receptor agonist WIN55,212-2 with mild therapeutic hypothermia and normothermic control on post-resuscitation myocardial function in a rat model of extracorporeal life support (ECLS)

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.

Background 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. Methods 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 \u3bcmol/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. Results S-NO-HSA, compared with HSA infusion, reduced RV afterload expressed by effective pulmonary arterial elastance (Ea; 0.49 \ub1 0.3 vs 1.2 \ub1 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 \ub1 0.17 to 0.94 \ub1 0.21; p = 0.005), but not HSA infusion, leading to positive effect on ventricular interdependence with increased left ventricular stroke volume (56% \ub1 4% vs 19% \ub1 5%; p = 0.0013). S-NO-HSA, compared with HSA, treatment improved adenosine 5\u2032-triphosphate (13.9 \ub1 1.1 vs 7.0 \ub1 1.8 \u3bcmol/g protein) and phosphocreatine (5.9 \ub1 3.3 vs 1.9 \ub1 0.6 \u3bcmol/g protein; p = 0.01) RV content and decreased the tissue oxidized glutathione/reduced glutathione ratio (p = 0.001). Conclusions 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

Dual modulation of no production in the heart during ischaemia/reperfusion injury and inflammation

Nitric oxide (NO) homeostasis maintained by neuronal/endothelial NO synthase (n/eNOS) contributes to regulate cardiac function under physiological conditions. At the early stages of ischaemia, NO homeostasis is disturbed due to Ca2+-dependent e/nNOS activation. In endothelial cells, successive drop in NO concentration may occur due to both uncoupling of eNOS and/or successive inhibition of nNOS catalytic activity mediated by arachidonic acid-induced tyrosine phosphorylation of this enzyme. The reduced NO bioavailability triggers nuclear factor-\u3baB activation followed by the induction of inducible NOS (iNOS) expression. In cardiomyocytes ischaemia also triggers the induction of iNOS expression during reperfusion. The massive amounts of NO which are subsequently produced following iNOS induction may exert on cardiomyocytes and the other cell types of cells of the heart, such as endothelial and smooth muscle cells, macrophages and neutrophils, opposing effects, either beneficial or toxic. The balance between these two double faceted actions may contribute to the final clinical outcomes, determining the degree of functional adaptation of the heart to ischaemia/reperfusion injury. In the light of this new vision on the critical role played by the cross-talk between n/eNOS and iNOS, we have reason to believe that new pharmacological measurements or experimental interventions, such as ischaemic preconditioning, aimed at counteracting the drop in NO levels beyond the normal range of NO homeostasis during early reperfusion can represent an efficient strategy to reduce the extent of functional impairment and cardiac damage in the heart exposed to ischaemia/reperfusion injury

Effects of polarizing microplegia vs standard high-potassium depolarizing microplegia on intracellular metabolism, pro-survival kinases, and apoptosis in humans.

Potassium-enriched depolarizing arrest (DA) is still the worldwide accepted method for myocardial protection. Despite animal models have demonstrated superior protection with no-potassium polarizing arrest (PA), and clinical studies reported lower perioperative myocardial enzymatic release, intra-cellular effects of PA vs DA in human myocardial specimens are still ill-defined

Tissue-based map of the human proteome

Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes.We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body

Tissue-based map of the human proteome

Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes.We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body