A new side effect of inhaled nitric oxide in neonates and infants with pulmonary hypertension: Functional impairment of the neutrophil respiratory burst

Gessler, Peter; Nebe, Thomas; Birle, Alexandra; Mueller, W; Kachel, W.

doi:10.1007/bf01712246

Cited by 43 publications

(18 citation statements)

References 34 publications

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“…This confirms and extends the results of several studies using in vitro methods of NO exposure to examine the effect of NO on neutrophils from adult animals [5][6][7][8]. Additionally, the data suggest that the depressive effect of NO on stimulated neutrophil CD18 expression is prevented by concurrent exposure to hyperoxia.…”

Section: Discussionsupporting

confidence: 77%

“…Antioxidant enzymes have shown beneficial effects against hyperoxiainduced lung injury. Although the dose of NO used in this study is relatively high, higher doses than 50 ppm are still occasionally used in humans [8]. Also, use of nitric oxide as treatment for severe BPD has been described with treatment durations as long as three months [38].…”

Section: Discussionmentioning

confidence: 99%

“…NO also is reported to decrease neutrophil superoxide anion (O 2 ) production and perhaps bactericidal capacity [7,8]. During the development of lung injury from hyperoxia, neutrophil accumulation in the lung parenchyma is a recognized early event [4,9].…”

mentioning

confidence: 99%

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Independent and Combined Effects of Prolonged Inhaled Nitric Oxide and Oxygen on Lung Inflammation in Newborn Piglets

et al. 1999

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Clinical use of nitric oxide (NO) is usually in conjunction with high oxygen concentrations, the effects of which may include lung neutrophil accumulation, apoptosis and upregulation of antioxidant enzyme activity. To define the effects of NO on neutrophils from young piglets and its relationship to lung neutrophil dynamics during hyperoxia we exposed thirty piglets to room air (RA), RA+NO (50 ppm NO), O₂ (FiO₂≥0.96) or O₂+NO for 5 days. Ten additional animals breathed RA+NO or O₂+NO, then recovered in RA for 3 days before sacrifice. Neutrophil CD18 and intracellular oxidant production were measured by flow cytometry. Lung apoptosis were assessed by TUNEL assay. Lung myeloperoxidase, SOD and catalase were measured biochemically. When compared to RA group, there was significant reduction in neutrophil CD18 and intracellular oxidant production in the RA+NO group, but lung MPO was unchanged. The O₂ and O₂+NO groups did not differ in CD18 expression or in intracellular oxidant production, but had significant increase in lung myeloperoxidase compared to the RA group. Apoptosis increased significantly only in the O₂+NO group. The O₂ group showed significantly increased lung SOD and catalase activity compared to the RA group, whereas the RA+NO and O₂+NO groups did not. We conclude that inhaled NO at 50 ppm decreases neutrophil CD18 expression as well as intracellular oxidant production. However, this effect does not impact lung neutrophil accumulation during concurrent hyperoxia. The combination of NO and O₂ exposure produces an increase in lung apoptosis. Finally, NO may prevent upregulation of SOD and catalase activity during hyperoxia, potentially increasing injury.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

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Independent and Combined Effects of Prolonged Inhaled Nitric Oxide and Oxygen on Lung Inflammation in Newborn Piglets

et al. 1999

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“…This contention is based on work by a number of laboratories reporting a subtle but prolonged nonadhesive, inhibitory effect of inhaled NO on neutrophils; 5 h after NO inhalation in swine caused neutrophil superoxide production to be reduced (35), an effect also reported in neonates that inhaled NO for 24-72 h (36). These effects were seen after prolonged incubation times, suggesting that NO was having a protracted inhibitory effect upon leukocytes.…”

Section: Discussionmentioning

confidence: 99%

Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds.

Fox-Robichaud

Payne²,

Hasan³

et al. 1998

J. Clin. Invest.

214

135

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Inhaled nitric oxide (NO) is being used more and more in intensive care units as a modality to improve the outcome of patients with pulmonary complications. Our objective was to demonstrate that inhaled NO could impact upon a distally inflamed microvasculature-improving perfusion, leukocyte adhesive interactions, and endothelial dysfunction. Using intravital microscopy to visualize ischemia/reperfusion of postcapillary venules, we were able to demonstrate that the reduction in perfusion, the dramatic increase in leukocyte rolling, adhesion, and emigration, and the endothelial dysfunction could all be significantly abrogated with 80 ppm, but not 20 ppm inhaled NO. Perfusing whole blood directly over an inert P-selectin and CD18 ligand substratum incorporated in a flow chamber recruited the same number of rolling and adhering leukocytes from NO-ventilated and non-NO-ventilated animals, suggesting that inhaled NO was not directly affecting leukocytes. To demonstrate that inhaled NO was actually reaching the peripheral microvasculature in vivo, we applied a NO synthase inhibitor locally to the feline mesentery and demonstrated that the vasoconstriction, as well as leukocyte recruitment, were essentially abolished by inhaled NO, suggesting that a NOdepleted peripheral microvasculature could be replenished with inhaled NO in vivo. Finally, inhaled NO at the same concentration that was effective in ischemia/reperfusion did not affect vascular alterations, leukocyte recruitment, and endothelial dysfunction associated with endotoxemia in the feline mesentery. In conclusion, our data for the first time demonstrate a role for inhaled NO as a therapeutic delivery system to the peripheral microvasculature, showing tremendous efficacy as an antiadhesive, antivasoconstrictive, and antipermeabilizing molecule in NO-depleted tissues, but not normal microvessels or vessels that have an abundance of NO (LPS-treated). The notion that blood borne molecules have NO carrying capacity is conceptually consistent with our observations. ( J. Clin. Invest. 1998. 101:2497-2505.)

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“…The oxidative burst can be altered, enhanced, or decreased by a number of substances and medical drugs such as antibiotics [36,54,55], nitric oxide [14], amphotericin B, lipid emulsions [29], and anesthetics [12,17]. It has been found that the oxidative burst is impaired during sepsis [13,32,47,53].…”

Section: Introductionmentioning

confidence: 98%

Oxidative burst measurement in patients treated with cytostatics: influence of G-CSF and role as a prognostic factor

Volk¹,

Kleine²,

Buthmann³

et al. 2000

Annals of Hematology

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The ability to generate reactive oxygen species, the so-called oxidative burst, is essential for neutrophils to kill infectious micro-organisms. Flow cytometry was used to study oxidative burst prior to, during, and after cytostatic therapy. Seven patients were treated according to the DexaBEAM regimen with 12 cycles monitored. Four patients were treated according to the B-NHL regimen in which nine cycles were monitored. Ten healthy volunteers were chosen as a control group without any treatment. Neutrophils were collected from heparinized peripheral blood and were stimulated by phorbol-12-myristate-13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP), and Escherichia coli. The oxidative burst was estimated by the amount of nonfluorescent dihydrorhodamine 123 converted to green fluorescent rhodamine 123. Measurements were done daily. The FMLP-induced burst was enhanced in patients before therapy as compared with the control group, whereas PMA-induced burst was decreased slightly. E. coli-, FMLP-, and PMA-induced oxidative burst decreased in both groups during cytostatic therapy. E. coli-induced burst increased again within 2 days of G-CSF treatment in vivo. FMLP-induced burst increased in the B-NHL group but decreased in the DexaBEAM group. In patients who have recovered from leukopenia the oxidative burst is still partly suppressed. PMA-induced oxidative burst measured at the start of therapy correlates with infectious complications. Thus, PMA-induced burst may be used as a simple method for evaluating the individual risk of infections during therapy. The results demonstrate the modulating effect of cytostatic drugs on the oxidative burst and may explain why some patients suffer from severe bacterial infections although the total number of granulocytes is normal.

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A new side effect of inhaled nitric oxide in neonates and infants with pulmonary hypertension: Functional impairment of the neutrophil respiratory burst

Cited by 43 publications

References 34 publications

Independent and Combined Effects of Prolonged Inhaled Nitric Oxide and Oxygen on Lung Inflammation in Newborn Piglets

Independent and Combined Effects of Prolonged Inhaled Nitric Oxide and Oxygen on Lung Inflammation in Newborn Piglets

Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds.

Oxidative burst measurement in patients treated with cytostatics: influence of G-CSF and role as a prognostic factor

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