Inhaled nitric oxide does not alter endotoxin-induced nitric oxide synthase activity during rat lung perfusion

1995 ◽  
Vol 79 (4) ◽  
pp. 1088-1092 ◽  
Author(s):  
M. M. Kurrek ◽  
L. Castillo ◽  
K. D. Bloch ◽  
S. R. Tannenbaum ◽  
W. M. Zapol
Keyword(s):  
Nitric Oxide ◽  
Feedback Inhibition ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
No Synthase ◽  
Rat Lung ◽  
Ex Vivo Lung Perfusion ◽  
Inducible No Synthase ◽  
Isolated Lung

Nitric oxide (NO) has been demonstrated to decrease its own synthesis in tissue preparations. We tested the hypothesis that endogenous NO synthesis induced by lipopolysaccharides (LPS) would be decreased by exogenous NO during isolated lung perfusion. Rats were pretreated with either saline or LPS 48 h before lung harvest. Endogenous NO synthase activity was measured as conversion of L-[14C]-arginine to L-[14C]citrulline during 90 min of perfusion. NO (100 ppm) was added to the ventilating gas during perfusion of lungs from one group of control or LPS-treated rats. A second group of control or LPS-treated rats was exposed chronically to 100 ppm NO for the 48 h before lung harvest, in addition to receiving 100 ppm NO added to the ventilating gas during lung perfusion. We conclude that conversion of L-[14C]arginine to L-[14C]citrulline was minimal in control lungs and increased in response to LPS pretreatment. NO added to the ventilating gas for the 90 min of ex vivo perfusion did not alter the rate of L-[14C]citrulline production. In vivo exposure to 100 ppm NO for 48 h did not alter the induction of inducible NO synthase activity as measured during ex vivo lung perfusion. This indicates that inhaled NO does not exert negative-feedback inhibition on inducible NO synthase in the ex vivo rat lung.

scholarly journals Isolated Lung Perfusion in the Management of Acute Respiratory Distress Syndrome

2020 ◽  
Vol 21 (18) ◽  
pp. 6820
Author(s):  
Nathan Haywood ◽  
Matthew R. Byler ◽  
Aimee Zhang ◽  
Mark E. Roeser ◽  
Irving L. Kron ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Ex Vivo Lung Perfusion ◽  
Isolated Lung Perfusion ◽  
Isolated Lung

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality, and current management has a dramatic impact on healthcare resource utilization. While our understanding of this disease has improved, the majority of treatment strategies remain supportive in nature and are associated with continued poor outcomes. There is a dramatic need for the development and breakthrough of new methods for the treatment of ARDS. Isolated machine lung perfusion is a promising surgical platform that has been associated with the rehabilitation of injured lungs and the induction of molecular and cellular changes in the lung, including upregulation of anti-inflammatory and regenerative pathways. Initially implemented in an ex vivo fashion to evaluate marginal donor lungs prior to transplantation, recent investigations of isolated lung perfusion have shifted in vivo and are focused on the management of ARDS. This review presents current tenants of ARDS management and isolated lung perfusion, with a focus on how ex vivo lung perfusion (EVLP) has paved the way for current investigations utilizing in vivo lung perfusion (IVLP) in the treatment of severe ARDS.

Comparison of the hemodynamic effects of nitric oxide and endothelium-dependent vasodilators in intact lungs

1990 ◽  
Vol 68 (2) ◽  
pp. 735-747 ◽  
Author(s):  
S. L. Archer ◽  
K. Rist ◽  
D. P. Nelson ◽  
E. G. DeMaster ◽  
N. Cowan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Pulmonary Hypertension ◽  
Feedback Inhibition ◽  
Pressor Response ◽  
Pulmonary Vasculature ◽  
Hemodynamic Effects ◽  
Isolated Lung

The effects of endothelium-dependent vasodilation on pulmonary vascular hemodynamics were evaluated in a variety of in vivo and in vitro models to determine 1) the comparability of the hemodynamic effects of acetylcholine (ACh), bradykinin (BK), nitric oxide (NO), and 8-bromo-guanosine 3′,5′-cyclic monophosphate (cGMP), 2) whether methylene blue is a useful inhibitor of endothelium-dependent relaxing factor (EDRF) activity in vivo, and 3) the effect of monocrotaline-induced pulmonary hypertension on the responsiveness of the pulmonary vasculature to ACh. In isolated rat lungs, which were preconstricted with hypoxia, ACh, BK, NO, and 8-bromo-cGMP caused pulmonary vasodilation, which was not inhibited by maximum tolerable doses of methylene blue. Methylene blue did not inhibit EDRF activity in any model, despite causing increased pulmonary vascular tone and responsiveness to various constrictor agents. There were significant differences in the hemodynamic characteristics of ACh, BK, and NO. In the isolated lung, BK and NO caused transient decreases of hypoxic vasoconstriction, whereas ACh caused more prolonged vasodilation. Pretreatment of these lungs with NO did not significantly inhibit ACh-induced vasodilation but caused BK to produce vasoconstriction. Tachyphylaxis, which was agonist specific, developed with repeated administration of ACh or BK but not NO. Tachyphylaxis probably resulted from inhibition of the endothelium-dependent vasodilation pathway proximal to NO synthesis, because it could be overcome by exogenous NO. Pretreatment with 8-bromo-cGMP decreased hypoxic pulmonary vasoconstriction and, even when the hypoxic pressor response had largely recovered, subsequent doses of ACh and NO failed to cause vasodilation, although BK produced vasoconstriction. These findings are compatible with the existence of feedback inhibition of the endothelium-dependent relaxation by elevation of cGMP levels. Responsiveness to ACh was retained in lungs with severe monocrotaline-induced pulmonary hypertension. Many of these findings would not have been predicted based on in vitro studies and illustrate the importance for expanding studies of EDRF to in vivo and ex vivo models.

Monitoring of endogenous nitric oxide exhaled by pig lungs during ex-vivo lung perfusion

2021 ◽  
Vol 15 (2) ◽  
pp. 027103
Author(s):  
Thibaut Chollier ◽  
Lucile Richard ◽  
Daniele Romanini ◽  
Angélique Brouta ◽  
Jean-Luc Martin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Ex Vivo Lung Perfusion ◽  
Endogenous Nitric Oxide

scholarly journals Nitric Oxide Measurements during Endotoxemia

2001 ◽  
Vol 47 (6) ◽  
pp. 1068-1074 ◽  
Author(s):  
Viktor Brovkovych ◽  
Lawrence W Dobrucki ◽  
Svitlana Brovkovych ◽  
Iwona Dobrucki ◽  
Leszek Kalinowski ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Total Concentration ◽  
Pulmonary Arteries ◽  
No Synthase ◽  
No Production ◽  
Subsequent Increase ◽  
Pathological Conditions ◽  
Inducible No Synthase

Abstract Background: Excessive continuous NO release from inducible NO synthase over prolonged periods under pathological conditions, such as endotoxemia, contributes significantly to circulatory failure, hypotension, and septic shock. This NO production during endotoxemia is accompanied by superoxide release, which contributes to the fast decay of NO. Therefore, the amount of NO that diffuses to target sites may be much lower than the total amount released under pathological conditions. Methods: We performed in vivo and ex vivo measurements of NO (electrochemical) and ex vivo in situ measurements of superoxide, peroxynitrite (chemiluminescence), and nitrite and nitrate (ultraviolet-visible spectroscopy). We determined the effect of lipopolysaccharide administration (20 mg/kg) on diffusible NO, total NO (diffusible plus consumed in chemical reactions), and superoxide and peroxynitrite release in the pulmonary arteries of rats. Results: An increase in diffusible NO generated by constitutive NO synthase was observed immediately after administration of lipopolysaccharide, reaching a plateau (145 ± 18 nmol/L) after 540 ± 25 s. The plateau was followed by a decrease in NO concentration and its subsequent gradual increase after 45 min because of NO production by inducible NO synthase. The concentration of superoxide increased from 16 ± 2 nmol/L to 30 ± 3 nmol/L after 1 h and reached a plateau of 41 ± 4 nmol/L after 6 h. In contrast to the periodic changes in the concentration of diffusible NO, the total concentration of NO measured as a sum of nitrite and nitrate increased steadily during the entire period of endotoxemia, from 2.8 ± 0.2 μmol/L to 10 ± 1.8 μmol/L. Conclusions: The direct measurement of NO concentrations in the rat pulmonary artery demonstrates dynamic changes throughout endotoxemia, which are related to the production of superoxide and the subsequent increase in peroxynitrite. Monitoring endotoxemia with total nitrate plus nitrite is not sensitive to these fluctuations in NO concentration.

scholarly journals Increased Arginase Expression and Decreased Nitric Oxide in Pig Donor Lungs after Normothermic Ex Vivo Lung Perfusion

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 300 ◽  
Author(s):  
Farshad Tavasoli ◽  
Mingyao Liu ◽  
Tiago Machuca ◽  
Riccardo Bonato ◽  
David R. Grant ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Transplantation ◽  
Lung Tissue ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Metabolizing Enzymes ◽  
Ex Vivo Lung Perfusion ◽  
Tissue Homogenates ◽  
Oxide Synthase ◽  
Nos Isoforms

An established pig lung transplantation model was used to study the effects of cold ischemia time, normothermic acellular ex vivo lung perfusion (EVLP) and reperfusion after lung transplantation on l-arginine/NO metabolism in lung tissue. Lung tissue homogenates were analyzed for NO metabolite (NOx) concentrations by chemiluminescent NO-analyzer technique, and l-arginine, l-ornithine, l-citrulline and asymmetric dimethylarginine (ADMA) quantified using liquid chromatography-mass spectrometry (LC-MS/MS). The expression of arginase and nitric oxide synthase (NOS) isoforms in lung was measured by real-time polymerase chain reaction. EVLP preservation resulted in a significant decrease in concentrations of NOx and l-citrulline, both products of NOS, at the end of EVLP and after reperfusion following transplantation, compared to control, respectively. The ratio of l-ornithine over l-citrulline, a marker of the balance between l-arginine metabolizing enzymes, was increased in the EVLP group prior to reperfusion. The expression of both arginase isoforms was increased from baseline 1 h post reperfusion in EVLP but not in the no-EVLP group. These data suggest that EVLP results in a shift of the l-arginine balance towards arginase, leading to NO deficiency in the lung. The arginase/NOS balance may, therefore, represent a therapeutic target to improve lung quality during EVLP and, subsequently, transplant outcomes.

scholarly journals The Establishment of an Ex Vivo Lung Perfusion in a Rat Lung Transplantation Model

2016 ◽  
Vol 35 (4) ◽  
pp. S179-S180
Author(s):  
A. Ohsumi ◽  
T. Kanou ◽  
T.K. Waddell ◽  
M. Liu ◽  
S. Keshavjee ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Rat Lung ◽  
Ex Vivo Lung Perfusion ◽  
Transplantation Model

In vivo lipopolysaccharide pretreatment inhibits cGMP release from the isolated-perfused rat lung

1995 ◽  
Vol 269 (5) ◽  
pp. L618-L624 ◽  
Author(s):  
M. M. Kurrek ◽  
W. M. Zapol ◽  
A. Holzmann ◽  
G. Filippov ◽  
M. Winkler ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Superoxide Dismutase ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
Rat Lung ◽  
Signal Transduction System ◽  
Endothelial No Synthase ◽  
Cgmp Signal

Administration of bacterial lipopolysaccharide (LPS) to rats stimulates synthesis of nitric oxide (NO), a free radical molecule that activates soluble guanylate cyclase, thereby increasing intracellular guanosine 3',5'-cyclic monophosphate (cGMP) concentration and inducing systemic vasodilatation. To investigate the effect of endotoxemia on the pulmonary NO/cGMP signal transduction system, we measured the release of cGMP by isolated-perfused lungs of rats that received an intraperitoneal injection of LPS (1 mg/kg) or saline 2 days earlier. Over 90 min, 1.4 +/- 0.78 and 0.079 +/- 0.016 nmol cGMP accumulated in pulmonary perfusates of saline- and LPS-treated rats, respectively (P < 0.05). Despite addition to the perfusate of Zaprinast, superoxide dismutase, or A23187, markedly less cGMP was released from the lungs of rats exposed to LPS than from the lungs of control rats. In contrast, after ventilation with 100 parts per million NO gas, cGMP accumulating in the perfusate of the lungs of both groups of rats was markedly increased, and the quantity of cGMP released from the lungs of LPS-treated rats was similar to that released by control rat lungs (2.8 +/- 0.57 vs. 3.3 +/- 0.88 nmol, P = NS). With the use of immunoblot techniques, equal concentrations of constitutive endothelial NO synthase were detected in the lungs of rats treated with saline or LPS. These results demonstrate that the NO/cGMP signal transduction system is abnormal in the lungs of rats exposed to LPS, at least in part, at the level of endothelial NO synthase activation.

SAFETY OF CONTINUOUS 12h DELIVERY OF ANTIMICROBIAL DOSES OF INHALED NITRIC OXIDE DURING EX VIVO LUNG PERFUSION

2020 ◽  
Author(s):  
Vinicius S. Michaelsen ◽  
Rafaela VP. Ribeiro ◽  
Aadil Ali ◽  
Aizhou Wang ◽  
Anajara Gazzalle ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Inhaled Nitric Oxide ◽  
Ex Vivo Lung Perfusion
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