Inhaled Nitric Oxide neither Alters Oxidative Stress Parameters nor Induces Lung Inflammation in Premature Lambs with Moderate Hyaline Membrane Disease

Abstract

The purpose of this investigation was to examine whether inhaled nitric oxide (NO) may alter oxidative stress parameters and induce lung inflammation in moderate hyaline membrane disease (HMD). Eighteen moderately premature lambs (130 days gestation, term = 147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n = 8) from the onset of ventilation or used as control (n = 10). Except inhaled NO, treatments were intentionally similar to those applied in clinical situations. The main studied parameters were oxidative stress index measurements on lung parenchyma and in circulating blood, lung parenchyma microscopic examination and bronchoalveolar lavage cell count. We found that 20 ppm of inhaled NO for 5 h did not change significantly either malondialdehyde and total antioxidant status levels in circulating blood, or malondialdehyde, reduced glutathione, glutathione peroxidase and glutathione reductase in lung parenchyma. Amino-imino-propene bond generation, which are lipoperoxidation markers, was similar in both groups. Furthermore, no significant changes in the number of inflammatory cells in lung lavage products and in lung parenchyma microscopic examination could be found. Therefore, these data do not support the hypothesis that short-term NO inhalation increases oxidative stress and lung inflammation in an experimental model of moderate HMD.

Inhaled nitric oxide therapy in premature newborns

“…In lambs delivered at 130 days gestation and mechanically ventilated for 5 hours with INO, there was no evidence of lung oxidative stress injury (lung malondialdehyde, reduced glutathione, glutathione reductase) compared to controls [16]. This finding is consistent with other studies on the role of INO in reducing oxidant stress [17][18][19].…”

Inhaled nitric oxide combined with prostacyclin and adrenomedullin in acute respiratory failure with pulmonary hypertension in piglets

“…11 The mechanism of action of ADM is not completely understood, but it probably depends only partially on NO pathway. 12,13 Moreover, previous studies demonstrated that iNO can promote [13][14][15][16][17] or attenuate [18][19][20] inflammatory and oxidative lung injuries, and affect surfactant function; [21][22][23] PGI 2 can contribute to decrease inflammatory processes 24 and oxidative cell damage; 25 and, finally, ADM can act as both pro-inflammatory and anti-inflammatory agent, [26][27] and decrease the oxidative cell stress. 28 Based on the above observations, we hypothesized that PH treatment with combined inhalation of both iNO plus PGI 2 , and iNO plus ADM might be more effective in lowering PAP and improving oxygenation than iNO alone.…”

Inhaled Nitric Oxide for the Treatment of Preterm Infants with Respiratory Distress Syndrome

“…Finding the optimal time for beginning iNO therapy is of the utmost importance since this factor might limit the duration of mechanical ventilation and oxygen therapy, which increase the risk of BPD promoting pulmonary inflammation [28][29][30][31][32] and oxidative damage [33][34][35][36] . In other words, the earlier the iNO therapy is started, when the lungs are less injured, the more effective BPD prevention might be.…”

“…Moreover, iNO treatment was associated with greater dynamic lung compliance, and decreased expiratory resistance. It is likely, therefore, that the beneficial effects of iNO on pulmonary function in this model of chronic lung disease reflect primarily nonsurfactant actions, such as anti-inflammatory [27][28][29][30][31] and antioxidant actions [32][33][34][35] . These results are in agreement with the observation that iNO increases lung compliance and tidal volume, and decreases airway resistance, without affecting surfactant surface activity in an animal model of acute lung injury [56] .…”

“…Moreover, BPD has been described as an arrest of lung development characterized by a reduced number of enlarged alveoli and intra-acinar arteries [23][24][25][26][27] . From this point of view, iNO might favor the prevention of BPD by preserving lung growth through several mechanisms: (1) attenuating pulmonary inflammation through reducing neutrophil accumulation in the lung and decreasing alveolar capillary permeability [28][29][30][31][32] , (2) protecting lung tissues against oxidative injuries [33][34][35][36] and (3) regulating pulmonary angiogenesis [37,38] , as demonstrated by McCurnin et al [39] in a baboon model of BPD.…”