Nitric oxide and the respiratory system (original) (raw)
Related papers
Inhaled Nitric Oxide for High-Altitude Pulmonary Edema
New England Journal of Medicine, 1996
Background. Pulmonary hypertension is a hallmark of high-altitude pulmonary edema and may contribute to its pathogenesis. When administered by inhalation, nitric oxide, an endothelium-derived relaxing factor, attenuates the pulmonary vasoconstriction produced by short-term hypoxia.
Effects Of Inhaled Nitric Oxide And Oxygen In High Altitude Pulmonary Edema
The use of inhaled nitric oxide in acutely ill patients with high altitude pulmonary edema was first reported in 1998. We demonstrated that both nitric oxide and oxygen cause an acute decrease in pulmonary artery pressure, intrapulmonary shunting and improvement in oxygenation. There appears to be an additive effect on pulmonary hemodynamics and an even greater effect on gas exchange when both oxygen and nitric oxide are delivered simultaneously. While further studies are necessary to determine the potential long-term benefits or adverse sequelae associated with nitric oxide use, this report suggests that there may be significant benefits for patients who are acutely ill with high altitude pulmonary edema. This report may also provide some insight into the mechanism whereby nitric oxide and oxygen improve gas exchange in a hypoxic hypobaric atmosphere. Keywords: Nitric oxide; hypoxic; high altitude pulmonary edema.
Inhaled Nitric Oxide: The authors reply
Critical Care Medicine, 1999
Inhaled nitric oxide (NO) plays an important role in treating persistent pulmonary hypertension of the newborn (PPHN), which is marked by a pathologic elevation of pulmonary vascular resistance. There is good evidence that the use of inhaled NO reduces the need for extracorporeal membrane oxygenation for term babies with severe PPHN of any cause, except in those infants with congenital diaphragmatic hernia, for which a benefit has not been shown. Although reducing the need for extracorporeal membrane oxygenation is beneficial in terms of cost and morbidity, inhaled NO has not been shown to decrease mortality in any neonatal population. Inhaled NO has also been shown to improve oxygenation in premature infants, although longer-term benefits have not been consistently demonstrated. This article will review the physiology of NO, its mechanisms of action in PPHN, and examine the evidence that supports its use in term and preterm infants with pulmonary hypertension.
Inhaled nitric oxide: clinical applications
Current Paediatrics, 1995
Up to a decade ago, nitric oxide (NO) was viewed primarily as a toxic gas responsible for a portion of the morbidity related to air pollution. In contrast, NO currently is recognised as a major endogenous mediator of an extraordinary range of functions including vascular regulation, neurotransmission, host defence and cytotoxicity. An increasing volume of literature has shown the importance of NO in the regulation of various cardiopulmonary functions and suggested its involvement in several disease processes. There is now compelling experimental evidence suggesting that inhaled NO may be beneficial in disease states characterised by pulmonary vasoconstriction and ventilationperfusion mismatch. 1 Several diseases of newborns and older children are characterised by potentially life threatening hypoxaemia due to ventilation-perfusion mismatch in the lungs associated with pulmonary vasoconstriction and pulmonary hypertension. Inhaled NO therapy may prove beneficial in a number of these conditions. NO pharmacology Endogenous NO is synthesised in vascular endothelial cells from arginine by the enzyme nitric oxide synthase. The generated NO diffuses into the neighbouring smooth muscle cells where it activates soluble guanylate cyclase to convert guanosine triphosphate into cyclic guanosine monophosphate (cGMP). The intracellular accumulation of cGMP leads to smooth muscle relaxation (Figure). The NO generated by NO synthase is short lived as
Pharmacology & Therapeutics, 1999
Nitric oxide is produced by many cell types in the lung and plays an important physiologic role in the regulation of pulmonary vasomotor tone by several known mechanisms. Nitric oxide stimulates soluble guanylyl cyclase, resulting in increased levels of cyclic GMP in lung smooth muscle cells. The gating of K ϩ and Ca 2 ϩ channels by cyclic GMP binding is thought to play a role in nitric oxide-mediated vasodilation. Nitric oxide may also regulate pulmonary vasodilation by direct activation of K ϩ channels or by modulating the expression and activity of angiotensin II receptors. Administration of nitric oxide by inhalation has been shown to acutely improve hypoxemia associated with pulmonary hypertension in humans and animals. This is presumably due to its ability to induce pulmonary vasodilation. Inhaled nitric oxide improves oxygenation and reduces the need for extracorporeal membrane oxygenation in term and near-term infants with persistent pulmonary hypertension. However, long-term benefits to these infants have been difficult to demonstrate. In other pathologic conditions, such as prematurity and acute respiratory distress syndrome, short-term benefits have not been shown conclusively to outweigh potential toxicities. For example, high-dose inhaled nitric oxide decreases surfactant function in the lung. Inhaled nitric oxide also acts as a pulmonary irritant, causing priming of lung macrophages and oxidative damage to lung epithelial cells. Conversely, protective effects of nitric oxide have been described in a number of pathological states, including hyperoxic and ischemia/reperfusion injury. Nitric oxide has also been reported to protect against oxidative damage induced by other reactive intermediates, including superoxide anion and hydroxyl radical. The dose and timing of nitric oxide administration needs to be ascertained in clinical trials before recommendations can be made regarding its optimal use in patients.
Nitric Oxide: A Positive Poison
Australian Critical Care, 1995
In 1987 the demonstration that nitric oxide WO) was formed in vascular endothelial cells opened up a vast area o f research. Ten years ago NO was viewed primarily a s a toxic gas related to air pollution. Today NO is recognised a s a major endogenous mediator o f multiple physiological processes. NO'S vasodilatory pmperties and short half life has led to the use o f inhaled NO a s a selective ~u lmonary vasodilator. NO was first used in neonates with acute pulmonary hypertension. It is now being used in the treatment o f critically ill adults with severe respiratory compromise. It is very likely that intensive care nursing staff will increasingly be asked to contribute to the maintenance and management o f NO inhalation therapy.
Randomised trial of three doses of inhaled nitric oxide in acute respiratory distress syndrome
Archives of Disease in Childhood, 1998
Background-Inhaled nitric oxide (iNO) is a potential therapeutic agent for the management of acute respiratory distress syndrome (ARDS). Concerns remain, however, regarding the potential toxicity from iNO and/or its oxidative derivatives and methaemoglobinaemia. Aims-To determine the risk of toxicity from iNO, which includes worsening of lung injury, a prospective study evaluating the acute eVects of three concentrations of iNO on gas exchange and haemodynamics in 12 children with ARDS was performed in a tertiary paediatric intensive care unit. Intervention-iNO was administered for one hour at three concentrations (1, 10, and 20 parts per million (ppm)) in a random order of possible dosing schedules to avoid dose accumulation bias. Arterial blood gas, methaemoglobin concentrations, and haemodynamic parameters were obtained at baseline before commencement of iNO, at the end of each study hour, and after iNO was discontinued. Nitric oxide and nitrogen dioxide concentrations were continuously monitored during the study. Results-iNO significantly improved the oxygenation ratio (PaO 2 /FiO 2) from a mean (SEM) baseline of 11.9 (1.7) kPa to 20 (3.9) kPa, 24 (4.5) kPa, and 21.6 (3.9) kPa at 1, 10, and 20 ppm iNO, respectively. There was no significant diVerence in the improvement in oxygenation achieved between the three concentrations. Correspondingly, there was a significant improvement in oxygenation index (pre-iNO 28.3 (5) v post-iNO 18 (3) (1 ppm), 15 (3) (10 ppm), 16 (3) (20 ppm)). No toxicity from methaemoglobinaemia or nitrogen dioxide was seen during iNO administration. Conclusion-The results show that a low concentration of iNO (1 ppm) is as eVective as higher concentrations (10 and 20 ppm) in improving oxygenation in children with ARDS and may be important in minimising toxicity during iNO use.