ESR spectral transition by arteriovenous cycle in nitric oxide hemoglobin of cytokine-treated rats

1994 ◽  
Vol 266 (5) ◽  
pp. C1400-C1405 ◽  
Author(s):  
H. Kosaka ◽  
Y. Sawai ◽  
H. Sakaguchi ◽  
E. Kumura ◽  
N. Harada ◽  
...  

Nitric oxide (NO) generation was induced in rats by Escherichia coli lipopolysaccharide (LPS) as detected by electron spin resonance (ESR) signals of NO hemoglobin (HbNO). However, there were inconsistencies in ESR spectral shape among them. We have therefore carried out a systematic study to clarify the in vivo spectral changes. First, the spectra of the alpha-NO heme species had the distinct three-line hyperfine structure in venous blood but not in arterial blood in all rats treated with tumor necrosis factor, interleukin-1, and/or LPS, and methemoglobin was not detected at the g = 6 (high-spin methemoglobin) region. Second, when the treated rats died, the three-line hyperfine structure was very distinct even in arterial blood. Third, even if HbNO was formed by injection of nitrite to rats, the three-line hyperfine structure of HbNO in venous blood was more marked than that in arterial blood, independent of the appearance of the methemoglobin signal. Fourth, an ex vivo study using whole blood demonstrated that the three-line hyperfine structure intensified lineally when O2 saturation of hemoglobin decreased but disappeared on reoxygenation of hemoglobin. These results directly demonstrate in vivo quaternary structural transition of the hemoglobin tetramer from the high-affinity state in the arterial cycle to the low-affinity state in the venous cycle. The transition makes the diverse ESR spectra of HbNO in vivo.

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 328
Author(s):  
Patrícia Dias ◽  
Jana Pourová ◽  
Marie Vopršalová ◽  
Iveta Nejmanová ◽  
Přemysl Mladěnka

Regular intake of polyphenol-rich food has been associated with a wide variety of beneficial health effects, including the prevention of cardiovascular diseases. However, the parent flavonoids have mostly low bioavailability and, hence, their metabolites have been hypothesized to be bioactive. One of these metabolites, 3-hydroxyphenylacetic acid (3-HPAA), formed by the gut microbiota, was previously reported to exert vasorelaxant effects ex vivo. The aim of this study was to shed more light on this effect in vivo, and to elucidate the mechanism of action. 3-HPAA gave rise to a dose-dependent decrease in arterial blood pressure when administered i.v. both as a bolus and infusion to spontaneously hypertensive rats. In contrast, no significant changes in heart rate were observed. In ex vivo experiments, where porcine hearts from a slaughterhouse were used to decrease the need for laboratory animals, 3-HPAA relaxed precontracted porcine coronary artery segments via a mechanism partially dependent on endothelium integrity. This relaxation was significantly impaired after endothelial nitric oxide synthase inhibition. In contrast, the blockade of SKCa or IKCa channels, or muscarinic receptors, did not affect 3-HPAA relaxation. Similarly, no effects of 3-HPAA on cyclooxygenase nor L-type calcium channels were observed. Thus, 3-HPAA decreases blood pressure in vivo via vessel relaxation, and this mechanism might be based on the release of nitric oxide by the endothelial layer.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dilmurodjon Eshmuminov ◽  
Dustin Becker ◽  
Max L. Hefti ◽  
Matteo Mueller ◽  
Catherine Hagedorn ◽  
...  

AbstractLong-term perfusion of liver grafts outside of the body may enable repair of poor-quality livers that are currently declined for transplantation, mitigating the global shortage of donor livers. In current ex vivo liver perfusion protocols, hyperoxic blood (arterial blood) is commonly delivered in the portal vein (PV). We perfused porcine livers for one week and investigated the effect of and mechanisms behind hyperoxia in the PV on hepatic arterial resistance. Applying PV hyperoxia in porcine livers (n = 5, arterial PV group), we observed an increased need for vasodilator Nitroprussiat (285 ± 162 ml/week) to maintain the reference hepatic artery flow of 0.25 l/min during ex vivo perfusion. With physiologic oxygenation (venous blood) in the PV the need for vasodilator could be reduced to 41 ± 34 ml/week (p = 0.011; n = 5, venous PV group). This phenomenon has not been reported previously, owing to the fact that such experiments are not feasible practically in vivo. We investigated the mechanism of the variation in HA resistance in response to blood oxygen saturation with a focus on the release of vasoactive substances, such as Endothelin 1 (ET-1) and nitric oxide (NO), at the protein and mRNA levels. However, no difference was found between groups for ET-1 and NO release. We propose direct oxygen sensing of endothelial cells and/or increased NO break down rate with hyperoxia as possible explanations for enhanced HA resistance.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Mona Soliman

Resuscitation following hemorrhagic shock result in myocardial contractile dysfunction and injury. We examined the protective effects of non-selective inhibitor of nitric oxide synthase N(G)-nitro-L-arginine methylester (L-NAME) on myocardial contractile function in the isolated perfused hearts, after ex vivo as well as in vivo treatment with L-NAME and resuscitation following one hour of hemorrhagic shock.Male Sprague Dawley rats (300-350 gm) were assigned to 2 sets of experimental protocols: ex vivo and in vivo treatment and resuscitation. Each set has 3 experimental groups (n= 6 per group): normotensive (N), hemorrhagic shock and resuscitation (HS-R) and hemorrhagic shock rats treated with L-NAME and resuscitated (HS- L-NAME-R). Rats were hemorrhaged over 60 min to reach a mean arterial blood pressure of 40 mmHg. In the ex vivo group, hearts were harvested and ex vivo treated and resuscitated by perfused in the Langendorff System. In the L-NAME treated group, L-NAME was added for the first 5 min . Cardiac function was measured Left ventricular generated pressure and +dP/dt were calculated. In the in vivo group, rats were treated with L-NAME intra-arterially after 60 min hemorrhagic shock. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30 min to restore normo-tension. Inhibition of nitric oxide synthase using L-NAME before resuscitation in ex vivo treated and resuscitated isolated hearts and in in vivo treated and resuscitated rats following hemorrhagic shock improved myocardial contractile function. Left ventricular generated pressure and + dP/dt max was significantly higher in L-NAME treated rats compared to the untreated group.Treatment with L-NAME improved left ventricular generated pressure following hemorrhagic shock in the ex vivo as well as the in vivo treated and resuscitated rats. The results indicate that L-NAME protects the myocardium against dysfunction by inhibiting NOS.


Sensors ◽  
2021 ◽  
Vol 21 (11) ◽  
pp. 3827
Author(s):  
Gemma Urbanos ◽  
Alberto Martín ◽  
Guillermo Vázquez ◽  
Marta Villanueva ◽  
Manuel Villa ◽  
...  

Hyperspectral imaging techniques (HSI) do not require contact with patients and are non-ionizing as well as non-invasive. As a consequence, they have been extensively applied in the medical field. HSI is being combined with machine learning (ML) processes to obtain models to assist in diagnosis. In particular, the combination of these techniques has proven to be a reliable aid in the differentiation of healthy and tumor tissue during brain tumor surgery. ML algorithms such as support vector machine (SVM), random forest (RF) and convolutional neural networks (CNN) are used to make predictions and provide in-vivo visualizations that may assist neurosurgeons in being more precise, hence reducing damages to healthy tissue. In this work, thirteen in-vivo hyperspectral images from twelve different patients with high-grade gliomas (grade III and IV) have been selected to train SVM, RF and CNN classifiers. Five different classes have been defined during the experiments: healthy tissue, tumor, venous blood vessel, arterial blood vessel and dura mater. Overall accuracy (OACC) results vary from 60% to 95% depending on the training conditions. Finally, as far as the contribution of each band to the OACC is concerned, the results obtained in this work are 3.81 times greater than those reported in the literature.


Author(s):  
A. A. Iakupova ◽  
S. R. Abdulkhakov ◽  
R. K. Zalyalov ◽  
A. G. Safin ◽  
R. A. Abdulkhakov

Aim. A literature review of intestinal permeability assessment techniques.Key points. The intestinal barrier is a functional entity separating the intestinal lumen and internal body, and intestinal permeability is a measure of the barrier functionality. The intestinal barrier integrity and permeability assays differ by the application setting (in vivo or ex vivo), subject (human or animal), marker molecules used to assess permeability (ions, various size carbohydrates, macromolecules, antigens, bacterial products and bacteria), biomaterial for the marker concentration assays (peripheral blood, portal venous blood, urine, stool). Despite a great variety of methods for assessing intestinal permeability, their clinical application requires further studies due to a lack of standardisation, the complexity of selected techniques and occasional limited reliability of results.Conclusion. Further investigation and improvement of intestinal permeability assays is required. The assay and result standardisation will facilitate practice in functional and organic intestinal diseases, as well as allergies, diabetes mellitus, non-alcoholic fatty liver disease and some other illnesses.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
T. Secher ◽  
F. Rodrigues Coelho ◽  
N. Noulin ◽  
A. Lino dos Santos Franco ◽  
V. Quesniaux ◽  
...  

Inhaled bacterial lipopolysaccharides (LPSs) induce an acute tumour necrosis factor-alpha (TNF-α-) dependent inflammatory response in the murine airways mediated by Toll-like receptor 4 (TLR4) via the myeloid differentiation MyD88 adaptor protein pathway. However, the contractile response of the bronchial smooth muscle and the role of endogenous TNFα in this process have been elusive. We determined the in vivo respiratory pattern of C57BL/6 mice after intranasal LPS administration with or without the presence of increasing doses of methacholine (MCh). We found that LPS administration altered the basal and MCh-evoked respiratory pattern that peaked at 90 min and decreased thereafter in the next 48 h, reaching basal levels 7 days later. We investigated in controlled ex vivo condition the isometric contraction of isolated tracheal rings in response to MCh cholinergic stimulation. We observed that preincubation of the tracheal rings with LPS for 90 min enhanced the subsequent MCh-induced contractile response (hyperreactivity), which was prevented by prior neutralization of TNFα with a specific antibody. Furthermore, hyperreactivity induced by LPS depended on an intact epithelium, whereas hyperreactivity induced by TNFα was well maintained in the absence of epithelium. Finally, the enhanced contractile response to MCh induced by LPS when compared with control mice was not observed in tracheal rings from TLR4- or TNF- or TNF-receptor-deficient mice. We conclude that bacterial endotoxin-mediated hyperreactivity of isolated tracheal rings to MCh depends upon TLR4 integrity that signals the activation of epithelium, which release endogenous TNFα.


1990 ◽  
Vol 183 (6) ◽  
pp. 2245-2246 ◽  
Author(s):  
F.Q. Cunha ◽  
R.A. Ribeiro ◽  
L.H. Faccioli ◽  
G.E.P. Souza ◽  
S.H. Ferreira

1995 ◽  
Vol 181 (6) ◽  
pp. 2237-2247 ◽  
Author(s):  
J A Roake ◽  
A S Rao ◽  
P J Morris ◽  
C P Larsen ◽  
D F Hankins ◽  
...  

Dendritic cells (DC) in nonlymphoid organs can internalize and process foreign antigens before migrating to secondary lymphoid tissues to initiate primary immune responses. However, there is little information on which stimuli promote migration of DC from the tissues. Systemic administration of lipopolysaccharide (LPS), which induces in vivo production of cytokines, led to a reduction in the numbers of major histocompatibility complex class II-positive (Ia+) leukocytes in mouse hearts and kidneys: > 95% of DC were depleted 1-3 d after injection of 50 micrograms LPS. Several lines of evidence indicated that this response was due to migration of DC rather than loss of Ia expression or cytotoxic effects. In skin of treated mice, the number of Ia+ epidermal Langerhans' cells (LC) was reduced, and "cords" of Ia+ leukocytes became evident in the dermis. The latter cells expressed little NLDC145 and may have originated from recruited or resident DC progenitors. Systemic administration of recombinant tumor necrosis factor (rhTNF)-alpha resulted in a decrease in numbers of Ia+ cells in heart and kidney and of epidermal LC, and it also induced dermal cords. Administration of a rh-interleukin (IL)-1 resulted in a decrease in Ia+ cells only in renal medulla, appeared to activate a subset of epidermal LC, and induced dermal cords. Similar microgram doses of rhIL-2 had no obvious effect. Treatment with a neutralizing anti-TNF antiserum before LPS administration inhibited the depletion of LC from skin but not from heart or kidney. Therefore, TNF-alpha and IL-1 alpha may promote DC migration from nonlymphoid tissues and may have differential effects on different DC populations, but it is unclear whether they act on DC directly or indirectly (e.g., via other cytokines).


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