Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.

Frostell, Claes; Fratacci, Marie-Dominique; Wain, John C.; Jones, Rosemary; Zapol, Warren M.

doi:10.1161/01.cir.83.6.2038

Cited by 1,039 publications

(455 citation statements)

References 35 publications

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“…Although the mechanism of this effect is unclear, it is conceivable that inhalation with NO-gasiinhibits the formation of NO, and hence NO2-, by alveolar macrophages and polymorphonuclear leucocytes. The finding that NO inhalation alone did not prevent the rise in plasma NO2-between 120 and 180 min may well be due to the fact that inhalation with NO-gas for several hours may itself result in an accumulation of NO2-in the plasma (Forstell et al, 1991). NO-gas inhalation therapy, but not infusion of L-NMMA prevented the high mortality caused by endotoxaemia in the pig.…”

Section: Mortalitymentioning

confidence: 91%

Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock

Klemm¹,

Thiemermann

Winklmaier³

et al. 1995

British J Pharmacology

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1 The present investigation compares the effects of intravenous infusion of the NO synthase inhibitor NG-monomethyl-L-argiine (L-NMMA) with that of an inhalation with NO gas in a porcine model of endotoxin (lipopolysaccharide, LPS) shock. In addition, the effects of the combination of these two treatments were also investigated. 2 Male pigs were anaesthetized and instrumented for the measurement of haemodynamic parameters. Blood samples were withdrawn at different time intervals for determination of blood gases, pH, and plasma levels of nitrite/nitrate and tumour necrosis factor. 3 Endotoxin infusion (15 tLg kg-' h-' for 3 h) caused a progressive fall in mean arterial blood pressure (MABP) and cardiac output (CO) and a biphasic increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistence (PVR). A continuous infusion of L-NMMA (0.1 mg kg' min-') significantly attenuated the fall in MABP, but did not affect MPAP, CO and PVR. NO-inhalation (50 p.p.m.) did not affect MABP, but significantly blunted the biphasic increase in MPAP and PVR and significantly delayed the fall in CO. The combination of L-NMMA infusion (0.1 mg kg-' min-') with NO-inhalation (50 p.p.m.) completely prevented the fall in MABP, significantly improved CO, and attenuated the biphasic increase in MPAP and PVR. 4 %Endotoxin also caused a decline in Pao2 and a rise of Paco2. Infusion of L-NMMA neither affected the fall in Pao2 nor the increase in Paco2. In contrast, inhalation with NO gas alone as well as the combined administration of L-NMMA infusion and NO-inhalation completely prevented the fall in Pao2 and significantly protected against the increase in Paco2. 5 Infusion of endotoxin for 180 min resulted in a mortality of 58%, which was not affected by L-NMMA (63%). In contrast, treatment of LPS-animals with either NO-inhalation alone or NOinhalation plus L-NMMA completely prevented mortality. 6 This investigation demonstrates that treatment with NO-inhalation, in order to prevent the dramatic increase in MPAP, PVR and the alterations in peripheral blood gases combined with systemic L-NMMA to improve systemic MABP and thus organ perfusion, may be a new therapeutic regimen in the treatment of septic shock.

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Section: Mortalitymentioning

confidence: 91%

Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock

Klemm¹,

Thiemermann

Winklmaier³

et al. 1995

British J Pharmacology

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“…Inhaled nitric oxide (iNO; INOmax ® , INO Therapeutics, Hampton, NJ, USA) selectively dilates the pulmonary vasculature, rapidly diffuses across the alveolar-capillary membrane, and binds to hemoglobin with minimal systemic effects [1,2]. In pivotal studies of late preterm and term neonates with hypoxic respiratory failure (HRF) and pulmonary hypertension (PH), iNO therapy has been shown to improve oxygenation and reduce the need for extracorporeal membrane oxygenation [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of inhaled nitric oxide in neonates with hypoxic respiratory failure and pulmonary hypertension: the Japanese experience

Suzuki

Togari

Potenziano

et al. 2018

Journal of Perinatal Medicine

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Objective: To analyze data from a registry of Japanese neonates with hypoxic respiratory failure associated with pulmonary hypertension (PH) to compare the effectiveness of inhaled nitric oxide (iNO) in neonates born <34 weeks vs. ≥34 weeks gestational age (GA). Materials and methods: iNO was administered according to approved Japanese product labeling. Study data were collected before iNO administration and at predefined intervals until discontinuation. Results: A total of 1,114 neonates were included (n = 431, <34 weeks GA; n = 675, ≥34 weeks GA; n = 8, missing age data). Mean decrease from baseline oxygenation index (OI) was similar in both age groups. OI reduction was more pronounced in the <34 weeks subgroups with baseline OI ≥25. Survival rates were similar in the <34 weeks GA and ≥34 weeks GA groups stratified by baseline OI (OI < 15, 89% vs. 93%; 15 ≤ OI < 25, 85% vs. 91%; 25 ≤ OI ≤ 40, 73% vs. 79%; OI > 40, 64% vs. 66%). Conclusion: iNO improved oxygenation in preterm neonates as effectively as in late preterm and term neonates, without negative impact on survival. If clinically significant PH is present, as measured by pulse oximetry or echocardiography, a therapeutic trial of iNO might be indicated for preterm neonates.

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“…1,2,5,6 Inhaled nitric oxide (iNO) has been shown to be an effective treatment for PPHN. [7][8][9][10] Several randomized clinical trials have shown that iNO significantly improves oxygenation and decreases the need of ECMO or incidence of death in near-term infants with hypoxic respiratory failure. [11][12][13] However, their response to iNO is not ideal and ranges between 50 and 60%.…”

Section: Introductionmentioning

confidence: 99%

Randomized controlled trial of early compared with delayed use of inhaled nitric oxide in newborns with a moderate respiratory failure and pulmonary hypertension

et al. 2009

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Objective: To evaluate whether early treatment with inhaled nitric oxide (iNO) will prevent newborns with moderate respiratory failure from developing severe hypoxemic respiratory failure (oxygenation index (OI)X40).Study Design: A total of 56 newborns with moderate respiratory failure (OI between 10 and 30) were randomized before 48 h after birth to early treatment with 20 p.p.m. of iNO (Early iNO group, n ¼ 28) or conventional mechanical ventilation with FiO 2 1.0 (Control group, n ¼ 28). Infants received iNO and/or high-frequency oscillatory ventilation (HFOV) if they developed an OI>40.Result: 7 of 28 early iNO patients (25%) compared to 17 of 28 control patients (61%) developed an OI>40 (P<0.05). In the Early iNO group mean OI significantly decreased from 22 (baseline) to 19 at 4 h (P<0.05) and remained lower over time: 19 (12 h), 18 (24 h) and 16 at 48 h. In contrast, OI increased in the Control group and remained significantly higher than the Early iNO group during the first 48 h of study: 22 (baseline), 29, 35, 32 and 23 at 4, 12, 24 and 48 h, respectively (P<0.01). Of 17, 6 control patients who developed an OI>40 were successfully treated with iNO. Nine of the remaining eleven control patients and six of seven Early iNO patients who had an OI>40 despite use of iNO responded with the addition of HFOV. One patient of the Early iNO group and two of the Control group died. Median (range) duration of oxygen therapy was significantly shorter in the Early iNO group: 11.5 (5 to 90) days compared to 18 (6 to 142) days of the Control group (P<0.03).Conclusion: Early use of iNO in newborns with moderate respiratory failure improves oxygenation and decreases the probability of developing severe hypoxemic respiratory failure.

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Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.

Cited by 1,039 publications

References 35 publications

Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock

Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock

Efficacy of inhaled nitric oxide in neonates with hypoxic respiratory failure and pulmonary hypertension: the Japanese experience

Randomized controlled trial of early compared with delayed use of inhaled nitric oxide in newborns with a moderate respiratory failure and pulmonary hypertension

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