Concentrations Of Inhaled Nitric Oxide Research Articles

Inhaled nasopharyngeal nitric oxide concentrations during unilateral nostril breathing – A pilot study

The yogic pranayama technique of unilateral nostril breathing (UNB) has previously demonstrated improvements in language and anxiety in stroke sufferers, as well as reduced blood pressure and increased heart rate in normal healthy adults. The nose typically passes different amounts of air through each nostril with the greater amount of air passing through the ‘patent’ side, and a lesser amount through the ‘congested’ side. Each side of the nose periodically takes turns at carrying the dominant tidal air flow in what is termed the’ nasal cycle’. The nasal sinuses are a rich source of inhaled nitric oxide, a colourless and odourless gas that acts as a bronchodilator, vasodilator, and neurotransmitter. Nasal derived nitric oxide (NO) may contribute to the benefits attributed to UNB. This investigation seeks to assess the influence the nasal cycle has on inhaled nasopharyngeal NO concentrations during UNB by comparing unobstructed bilateral nostril breathing to patent-side and congested-side UNB in healthy individuals demonstrating a nasal cycle.After determining the patent and congested nasal sides in healthy adult volunteers, and sampling air at both nostrils, nasopharyngeal inhaled NO concentrations were then assessed during normal nasal at-rest tidal breathing during three different nasal breathing states: first both nostrils, then allocated in randomised order, patent side only, and congested side with only UNB.Nasopharyngeal NO concentrations were found to be consistently higher on both exhalation and inhalation during congested side UNB, when compared with either unilateral patent side UNB or breathing through both nostrils.

Inhaled Nitric Oxide: In Vitro Analysis of Continuous Flow Noninvasive Delivery via Nasal Cannula.

Inhaled nitric oxide (NO) is most frequently delivered to mechanically ventilated patients in critical care, but it can also be administered noninvasively. The delivered dose and efficiency of continuous flow NO supplied through a nasal cannula has yet to be established. This study aimed to determine the influence of nasal cannula type, supply flow, and breathing pattern on delivered NO using a realistic adult airway replica and lung simulator. Simulated breathing patterns were selected to represent rest, sleep, and light exercise, and were varied to investigate the effects of tidal volume and breathing frequency independently. Supplied gas flows targeted tracheal concentrations at rest of 5 or 20 ppm NO and were supplied with 2 L/min O2. Three different cannulas were tested. Tracheal NO concentrations and NO mass flow past the trachea were evaluated. Cannula type had a minor influence on delivered dose. Tracheal NO concentrations differed significantly based on breathing pattern (P < 0.01); for a target NO concentration of 20 ppm at rest, average inhaled NO concentrations were 23.3 ± 0.5 ppm, 36.5 ± 1.4 ppm, and 17.2 ± 0.3 ppm for the rest, sleep, and light exercise breathing patterns, respectively. For the same test conditions, mass flow of NO past the trachea was less sensitive to breathing pattern: 20.3 ± 0.5 mg/h, 19.9 ± 0.8 mg/h, and 24.3 ± 0.4 mg/h for the rest, sleep, and light exercise breathing patterns, respectively. Mass flow and delivery efficiency increased when minute volume increased. These results indicate that inhaled NO concentration is strongly influenced by breathing pattern, whereas inhaled NO mass flow is not. NO mass flow may therefore be a useful dose metric for continuous flow delivery via nasal cannula.

Role Of Inhaled Nitric Oxides In Pregnancy With Eisenmenger Syndrome

ABSTRACTEisenmenger Syndrome (ES) is congenital heart disease with pulmonary hypertension and shunting turning from right to left. The resistance of pulmonary vascular more than 7.5 mmHg/L/min. The right ventricle and pulmonary artery always enlarge. During pregnancy, there will be hemodynamic changes that will affect the ES. It can be understood the possible dangers that can occur, like right heart failure; an increase in pulmonary arteries or the aggravation of pulmonary hypertension because there is no decrease in pulmonary resistance; A sudden decrease in venous return in supine hypotension syndrome can cause a relative increase in pulmonary arterial pressure so as to aggravate pulmonary hypertension and reverse shunting.Physiological effects of inhaled nitric oxide (INO) therapy cause selective pulmonary vasodilation: Hypoxia alveoli causes reversible vasoconstriction, thereby increasing pulmonary wedge pressure. INO can lower it. Moderate cardiac output and systematic arterial pressure are not affected; Selective in pulmonary because it is activated by hemoglobin; Selective vasodilation in the ventilated area, local hypoxia alveoli constricts the surrounding vascular tissue and redistributes blood flow to the ventilated lungs better and higher intraalveolar oxygen pressure. INO enhances this mechanism by increasing blood flow through a well-ventilated lung; Bronchodilators; Pulmonary surfactant, The combination of high concentrations of inspired oxygen and high concentrations of INO reduces the minimum surfactant surface tension.Keywords: Inhalation Nitric Oxides, Pregnancy, Eisenmenger Syndrome

Measurement of Exhaled Nitric Oxide Using End Tidal Value during Normal Breathing

Increased nitric oxide (NO) production in the expired air has been associated with a number of disease conditions and may reflect the severity of inflammation in the lungs. Measurement of exhaled NO concentration has been proposed as a novel clinical tool for assessing airway inflammation and response to drug therapy. In spite of international guidelines aimed at standardizing the measurement of exhaled NO, clinicians remain skeptical due to the necessity of a significant degree of subject collaboration required by the procedure to obtain meaningful measurements. We hypothesized that exhaled NO concentration may be best measured by using end tidal NO concentration during a breath by breath monitoring. We tested laboratory staff and monitored their NO concentration online using a fast response chemiluminescence NO analyzer during normal breathing at rest for 5 minutes. First we confirmed that the NO analyzer was adequately fast to record fully the swings during normal breathing. We then compared the average end tidal NO value (NOet) from 6 to 10 breaths, to the NO value obtained from the plateau from a single slow vital capacity maneuver as recommended by the ATS guidelines (NOplat). End of exhalation was identified using end tidal carbon dioxide measurement. NOet while breathing room air was 24.3 ± 4.2 (SE) ppb and was not significantly different compared to 22.4 ± 2.8 (SE) ppb using NOplat. Additionally breathing high level of NO of up to 88 ppb did not affect either NOet or NOplat significantly suggesting that both measurements are independent of inhaled NO concentration. NO value at end of exhalation was very reproducible from breath to breath and did not require any special effort on the part of the subject. We recommend using NOet measurement instead of the NOplat value that is highly dependent on the exhalation rate and cooperation of the subject. NOet is much easier to record in children, elderly and patients with respiratory disease. The main requirement for measuring NOet is to have a fast response NO analyzer to record the full swings in NO concentration during normal breathing and to have a way of identifying end exhalation.

Decreased Nitric Oxide Concentration When Used in Conjunction with the AnaConDa Device

To the Editor The Anaesthetic Conserving Device AnaConDa© (ACD) (Sedana Medical, Uppsala, Sweden) is a small vaporizer inserted into a ventilator circuit that allows vaporization of liquid sevoflurane from a syringe pump, and has been used to deliver volatile anesthetics for sedation of patients in the intensive care unit.1 We recently cared for such a patient receiving inhaled nitric oxide (NO), the concentration of which appeared to be altered by the ACD. A 64-year-old man, with severe chronic obstructive pulmonary disease and hypertension, underwent both aortic and mitral valve replacement. Permission was obtained from the patient for this report. Postoperatively, severe pulmonary hypertension and right ventricular failure required treatment with levosimendan, dobutamine, epinephrine, and inhaled NO at 16 ppm. NO concentrations were monitored using the NOxBOX© (Bedfont Medical, Kent, England). The patient later developed pneumonia and acute respiratory distress syndrome with increasing hypoxia, and the method of sedation was changed from intermittent midazolam to sevoflurane administered via the ACD. While aiming for Bispectral Index values between 60 to 70, an end-tidal concentration of sevoflurane between 0.5% and 0.7% was accompanied by a decrease in the hemoglobin oxygen saturation (SpO2) from 96% to 91%. The NO concentration measured at 2 sites in the system both before and after using the ACD revealed a 50% decrease in the concentration measured after using the ACD. Changing the site of NO delivery into the breathing system after rather than before using the ACD resulted in an increased inspired NO concentration to 16 ppm and an increased SpO2 of 98%. We hypothesize that the decreased SpO2 was related to decreased inhaled NO concentration caused by absorption of NO in the carbon-activated filter of the ACD.2–4 Jose Luis Guerrero Orriach Manuel Galan Ortega Manuel Rubio Navarro Jose Cruz Manñas Anesthesia Department Hospital Virgen de la Victoria Malaga, Spain [email protected]

A 5-Year Survey of Nitric Oxide Use in a Pediatric Intensive Care Unit

The authors retrospectively reviewed their experience with nitric oxide (NO) in a pediatric ICU. Given its cost ($3000/d), ongoing evaluations are required to ensure its effective use and avoid inappropriate applications. NO use included 4 categories: (1) hypoxemic respiratory failure, (2) pulmonary hypertension following surgery for congenital heart disease (CHD), (3) intraoperatively for surgical procedures such BT shunt placement or 1-lung ventilation, and (4) during ECMO. In the 19 patients with respiratory failure, NO resulted in an increase in oxygenation in 15 of 19 patients (Pao2/Fio2 ratio increased from 83 +/- 60 mm Hg to 188 +/- 105 mm Hg, P = 0.0007). In 4 patients, NO did not improve oxygenation. The 15 patients that responded to NO survived, whereas the 4 patients who did not respond died (P = 0.0003). NO was used to treat pulmonary hypertension in 19 patients following cardiopulmonary bypass (CPB) and surgery for CHD. In 13 of 19 patients, a high pulmonary artery (PA) pressure was documented by direct measurement with a needle inserted into the PA while the chest was open (n = 9) or a postoperative transthoracic PA catheter (n = 4). NO resulted in a decrease in the PA pressure in 9 of 13 patients (37 +/- 5 mm Hg to 21 +/- 3 mm Hg, P < 0.0001). In the one patient in whom NO did not lower intraoperative PA pressure, it was not possible to wean from CPB. For the 10 patients in whom NO was started in the PICU, 4 had PA catheters in place and documented elevated PA pressure. NO resulted in a significant decrease in the PA pressure in only 1 of these 4 patients. The survival of responders was 9 of 9 versus 1 of 4 for nonresponders (P = 0.014). No significant adverse effects requiring therapy other than decreasing the inhaled NO concentration were noted. Potential interventions and practices to limit the unwarranted use of this costly agent are discussed.

The Initial Response to Inhaled Nitric Oxide Treatment for Intensive Care Unit Patients with Acute Respiratory Distress Syndrome

Background: Inhaled nitric oxide (INO) can improve hypoxemia and reduce pulmonary hypertension, but there is a wide range of response to INO. Objectives: The aim of this study was to evaluate the effect of different INO concentrations in acute respiratory distress syndrome (ARDS) patients. Methods: Thirty-two adult ARDS patients who were supported by mechanical ventilator were included. INO was given at a concentration of 1, 5, 10, 20 and 40 ppm, sequentially. Arterial blood gas and mean pulmonary artery pressure (MPAP) were measured 30 min after INO concentrations changed. Results: There was a significant increase in PaO₂/FiO₂ (p < 0.0001) and a decrease in pulmonary vascular resistance index and MPAP (p < 0.0001) after INO use. INO concentrations required for improving oxygenation were in the range of 1–20 ppm, whereas concentrations required for decreasing MPAP were in the range of 1–40 ppm. PaO₂/FiO₂ worsened when the INO dose was adjusted above 20 ppm. Sixty-nine percent of ARDS patients were responders; 31% of them were nonresponders. Among responders, 64% of patients responded at 1 ppm, 36% at 5 ppm. Conclusions: The optimal doses for improving oxygenation and reducing PAP differ. The maximum PaO₂/FiO₂ was observed at a lower INO concentration than that required for the minimal MPAP. There was no further improvement in PaO₂/FiO₂ when the INO dose was adjusted above 20 ppm. Higher doses of INO treatment worsened oxygenation.

Pulmonary arterial dilation by inhaled NO: arterial diameter, NO concentration relationship.

The objective of this study was to determine the nitric oxide (NO) concentration and vessel diameter dependence of the pulmonary arterial dilation induced by inhaled NO. Isolated dog lung lobes were situated between a microfocal X-ray source and X-ray detector and perfused with either blood or plasma. Boluses of radiopaque contrast medium were injected into the lobar artery under control conditions, when the pulmonary arteries were constricted by infusion of serotonin and when the serotonin infusion was accompanied by inhalation of from 30 to 960 parts/million NO. Arterial diameter measurements were obtained from X-ray images of vessels having control diameters in the 300- to 3,400-microm range. Serotonin constricted the vessels throughout the size range studied, with an average decrease in diameter of approximately 20%. The fractional reversal of the serotonin-induced constriction by inhaled NO was directly proportional to inhaled NO concentration, inversely proportional to vessel size, and greater with plasma than with blood perfusion in vessels as large as 3 mm in diameter. The latter indicates that intravascular hemoglobin affected the bronchoalveolar-to-arterial luminal NO concentration gradient in fairly large pulmonary arteries. The data provide information regarding pulmonary arterial smooth muscle accessibility to intrapulmonary gas that should be useful as part of the database for modeling the communication between intrapulmonary gas and pulmonary arterial smooth muscle cells in future studies.

Nasal nitric oxide and the nasal cycle.

To establish the relationship between nasal patency and the nitric oxide (NO) concentration in the nasal airways. Unilateral nasal NO concentration (n = 11) and inhaled nasal NO concentration at oropharynx (n = 9) were measured in healthy adult volunteers. Subjects breathed normally through the nose with a known resistance (ranged from none to total occlusion) placed in one nostril. In a subgroup (n = 7), the unilateral nasal NO concentrations were determined with nasal cavity congestion induced by lateral decubitus. When the added nasal resistance was less than 6 cm H(2)0 per liter per second, the peak NO concentrations in the nose remained below 80 parts per billion (ppb). Thereafter, the higher the resistance, the greater the NO concentration. It was up to 1109.7 ppb when the front nostril was totally occluded. There was no correlation between oropharyngeal NO concentrations and resistance in the front of the nose (r = 0.4). There was a significantly negative correlation between nasal cavity volumes and nasal NO concentrations (r = -0.8, P <.001). Increases in nasal resistance to levels encountered in the nasal cycle and in recumbency augments the NO concentration within the obstructed side of the nose. Although that within the nose changes with patency, the NO concentration is constant down to the lower airways. The modulation role of the upper airways to the inhaled NO concentration remains unclear.

Changes in arterial oxygen tension when weaning neonates from inhaled nitric oxide*†

We set out to evaluate changes in arterial oxygen tension (PaO(2)) when weaning neonates from inhaled nitric oxide (INO). We reviewed the records of 505 prospectively collected INO weaning attempts on 84 neonates with hypoxic respiratory failure. PaO(2) values before and 30 min after weaning attempts were recorded. Relationships between change in PaO(2) and decreases in INO concentrations were investigated using regression analysis and ANOVA. PaO(2) decreased (-18.7 +/- 1.8 torr; P < 0.001); when weaning INO. A stepwise decline in PaO(2) was observed weaning INO from 40 ppm. The greatest decline occurred when INO was discontinued (-42.1 +/- 4.1 torr). Forward stepwise multiple regression using variables with significant relationships to the decline in PaO(2) identified the specific dose reduction 7(P < 0.001), the prewean PaO(2) (P < 0.001), and surfactant therapy (P = 0.018) as the variables best describing the change in PaO(2)(P = 0.004, r = 0.51). In conclusion, a graded decline in PaO(2) occurs when reducing INO. INO should be weaned to less than 1 ppm before discontinuing its use. Prior surfactant treatment appears to enhance the oxygenation reserve when weaning INO.

Inhaled nitric oxide improves survival rates during hypoxia in a sickle cell (SAD) mouse model.

The hallmark of sickle cell disease (SCD) is erythrocyte sickling during deoxygenation of the abnormal hemoglobin S (HbS). When HbS is deoxygenated, it aggregates into polymers, resulting in distortion of the erythrocyte structure, producing microvascular thrombosis and ischemia. The transgenic SAD mouse produces three types of human hemoglobin: S, Antilles, and D-Punjab (HbSAD) and provides an animal model for SCD. We studied the effects of nitric oxide (NO) breathing at various doses and time regimens in the presence of severe hypoxia (6% oxygen) using the SAD mouse model. Age- and sex-matched control and SAD mice were exposed to 6% oxygen breathing in an environmental chamber and assessed for survival up to 1 h. Animals received different inhaled NO concentrations before and/or during hypoxia. Blood was obtained to evaluate the oxyhemoglobin dissociation curve and measure methemoglobinemia. Pretreatment by breathing NO at 20 ppm by volume in air for 30 min, and continuing to breathe 20 ppm NO during hypoxia resulted in improvement in survival rates in the SAD mouse (75%, n = 8) as compared with control SAD mice (11%, n = 9; P < 0.001). Pretreatment alone or breathing lower doses of NO were not protective. Changes in HbSAD oxygen affinity were not detected with NO breathing, and methemoglobin levels were low in all surviving mice. Breathing NO produced a rapid, protective effect to severe hypoxic stress in SAD mice. There appears to be a required loading period between NO breathing and its beneficial effect during hypoxic stress, possibly because of the total amount of NO delivered to SAD hemoglobin, blood cell components, and endothelium. NO breathing may be beneficial as a therapeutic intervention in SCD.

Helium inhalation enhances vasodilator effect of inhaled nitric oxide on pulmonary vessels in hypoxic dogs

There are theoretical and experimental indications that the presence of He as a balance gas markedly increase the diffusion velocity of other gases contained in a gas mixture. We allowed dogs with pulmonary vasoconstriction induced by hypoxia to inhale a mixture of 5 parts per million (ppm) of nitric oxide (NO) and O(2) balanced with He (NO in He) instead of N(2) (NO in N(2)). The dilating effect of NO in He and NO in N(2) on the pulmonary artery was evaluated by determining conventional pulmonary hemodynamic parameters, mean pulmonary artery (PA) pressure (MPAP), and pulmonary vascular resistance indexed to body surface area (PVRI), pulmonary impedance (Z), and the recently developed hemodynamic index, time-corrected wave intensity (WI). The main findings in this study were as follows: 1) hypoxia increased MPAP, PVRI, Z at 0 Hz (Z(0)), Z at the first harmonics, characteristic impedance (Z(c)), the reflection coefficient (Gamma), and the first peak of WI; 2) NO in N(2) reduced Z(0) and Gamma; and 3) NO in He reduced the first peak of WI and reduced Z(0) and Gamma more than NO in N(2). The enhanced vasodilatory effect of NO in He might be associated with facilitated diffusion of NO diluted in the gas mixture with He. In conclusion, increased efficacy of NO in He offers the possibility to reduce the inhaled NO concentration.

Effect of inhaled nitric oxide on experimentally induced pulmonary hypertension in neonatal foals

Abstract Objective To evaluate the efficacy of inhaled nitric oxide (NO) in anesthetized healthy newborn foals with experimentally induced pulmonary hypertension. Animals Five 1- to 3-day-old foals. Procedure Anesthesia was induced and maintained with propofol, and foals were intubated and mechanically ventilated. Systemic pressure and pulmonary arterial pressure (PPA) were recorded every 30 seconds. Hypertension was induced via a hypoxic gas mixture or chemical vasoconstriction, using the thromboxane mimetic U46619. Nitric oxide was added at a concentration of 80 parts per million (ppm) for 6 minutes under baseline conditions and during pulmonary hypertension-induced alveolar hypoxia (inspired oxygen concentration = 0.08). Nitric oxide (20, 40, 80, and 160 ppm) was evaluated during U46619-induced hypertension. Samples for determination of arterial blood gas tensions were collected before and after each NO treatment. Results Inhaled NO (approx 80 ppm) did not have an effect on baseline variables. Infusion of U46619 (0.35 ± 0.04 μg/kg of body weight/min) or alveolar hypoxia resulted in increased PPA and decreased arterial oxygenation (Pao2) and hemoglobin saturation (HbSat). The increase in PPA was attenuated, in a dose-dependent manner, by NO during U46619 infusion and reversed by NO during induced hypoxemia. The Pao2 and HbSat were significantly improved at all NO doses during U44619 infusion but not during alveolar hypoxia. For all inhaled NO concentrations, nitrogen dioxide and methoglobin values were &lt; 5 ppm and 3%, respectively. Conclusions and Clinical Relevance Nitric oxide is a potent, selective vasodilator of the pulmonary circulation in healthy newborn foals. Inhaled NO may have value as a therapeutic agent in foals with pulmonary hypertension. (Am J Vet Res 1999;60:1207–1212)

The metabolic fate of long-term inhaled nitric oxide

Purpose: The fate of inhaled nitric oxide (NO) has not been precisely defined in critically ill patients. This study aimed at defining the effects of long-term NO inhalation on circulating NO byproduct levels. Material and Methods: During NO therapy, plasma and urine from 13 critically ill patients were sampled daily for determination of the stable byproducts of NO (nitrite [NO 2 −] and nitrate [NO 3 −]. Routine monitoring data included inhaled NO concentration, hemodynamic parameters, arterial blood gases, creatinine clearance, and C-reactive protein. Results: For the first 24 hours of NO inhalation (6.3 ± 1.1 ppm), NO 3 − plasma concentration increased (from 13.3 ± 5.4 to 52.3 ± 17.6 μmol/L), but NO 2 − plasma concentration was not affected. The NO 3 − plasma concentration was correlated with the C-reactive protein level, the inhaled NO concentration. Renal excretion of NO metabolites was unaltered by NO inhalation. The N0 3 concentrations returned to baseline when NO therapy was discontinued. Conclusion: Long-term NO inhalation was associated with a consistent increase in the NO 3 − plasma concentration. NO byproducts may be implicated in the systemic effects associated with this treatment.

Effect of nitric oxide on oxygenation and hemodynamics in infants after cardiac surgery.

We evaluated the effect of nitric oxide (NO) on infants after congenital cardiac surgery. Inhaled NO was administered to 7 infants after congenital cardiac surgery. Inhaled NO concentration ranged from 2.5 to 10 parts per million (ppm). The respiratory index (RI = A-aDO2/PaO2) decreased from 7.4 +/- 2.5 to 4.7 +/- 3.1 in the right RI group (RI > or = 3, n = 4) 30 min after NO inhalation. After discontinuation of NO inhalation, RI increased to the preinhalation level. NO inhalation was restarted in 2 patients in the high RI group because of severe worsening of oxygenation. RI was not affected by starting or discontinuing of NO in the low RI group (RI < 3, n = 3). Systemic blood pressure did not significantly change in the 2 groups. Pulmonary arterial pressure (PAP) was measured in 4 patients, and it decreased by 21, 10, and 10%, respectively, 30 min after NO inhalation in 3 patients, but did not change in the remaining patient. After discontinuation of NO inhalation, PAP increased in all patients, and in 2 cases, PAP was higher than baseline value. NO inhalation is effective in improving oxygenation in infants with a high RI after cardiac surgery. However, careful monitoring of the respiratory and hemodynamic states is required after discontinuing NO inhalation.

Inhaled nitric oxide in acute respiratory failure: Dose-response curves

To determine the dose-response curve of inhaled nitric oxide (NO) in terms of pulmonary vasodilation and improvement in PaO2 in adults with severe acute respiratory failure. Prospective randomized study. A 14-bed ICU in a teaching hospital. 6 critically ill patients with severe acute respiratory failure (lung injury severity score > or = 2.5) and pulmonary hypertension. 8 concentrations of inhaled NO were administered at random: 100, 400, 700, 1000, 1300, 1600, 1900 and 5000 parts per billion (ppb). Control measurements were performed before NO inhalation and after the last concentration administered. After an NO exposure of 15-20 min, hemodynamic parameters obtained from a fiberoptic Swan-Ganz catheter, blood gases, methemoglobin blood concentrations and intratracheal NO and nitrogen dioxide (NO2) concentrations, continuously monitored using a bedside chemiluminescence apparatus, were recorded on a Gould ES 1000 recorder. In 2 patients end-tidal CO2 was also recorded. The administration of 100-2000 ppb of inhaled NO induced: i) a dose-dependent decrease in pulmonary artery pressure and in pulmonary vascular resistance (maximum decrease--25%); ii) a dose-dependent increase in PaO2 via a dose-dependent reduction in pulmonary shunt; iii) a slight but significant decrease in PaCO2 via a reduction in alveolar dead space; iv) a dose-dependent increase in mixed venous oxygen saturation (SVO2). Systemic hemodynamic variables and methemoglobin blood concentrations did not change. Maximum NO2 concentrations never exceeded 165 ppb. In 2 patients, 91% and 74% of the pulmonary vasodilation was obtained for inhaled NO concentrations of 100 ppb. In hypoxemic patients with pulmonary hypertension and severe acute respiratory failure, therapeutic inhaled NO concentrations are in the range 100-2000 ppb. The risk of toxicity related to NO inhalation is therefore markedly reduced. Continuous SVO2 monitoring appears useful at the bedside for determining optimum therapeutic inhaled NO concentrations in a given patient.

Bronchodilator Action of Inhaled Nitric Oxide in Guinea Pigs

DUPUY, P. M.; SHORE, S. A.; DRAZEN, J. M.; FROSTELL, C.; HILL, W. A.; ZAPOL, W. M.Author Information

Bronchodilator action of inhaled nitric oxide in guinea pigs.

The effects of inhaling nitric oxide (NO) on airway mechanics were studied in anesthetized and mechanically ventilated guinea pigs. In animals without induced bronchoconstriction, breathing 300 ppm NO decreased baseline pulmonary resistance (RL) from 0.138 +/- 0.004 (mean +/- SE) to 0.125 +/- 0.002 cmH2O/ml.s (P less than 0.05). When an intravenous infusion of methacholine (3.5-12 micrograms/kg.min) was used to increase RL from 0.143 +/- 0.008 to 0.474 +/- 0.041 cmH2O/ml.s (P less than 0.05), inhalation of 5-300 ppm NO-containing gas mixtures produced a dose-related, rapid, consistent, and reversible reduction of RL and an increase of dynamic lung compliance. The onset of bronchodilation was rapid, beginning within 30 s after commencing inhalation. An inhaled NO concentration of 15.0 +/- 2.1 ppm was required to reduce RL by 50% of the induced bronchoconstriction. Inhalation of 100 ppm NO for 1 h did not produce tolerance to its bronchodilator effect nor did it induce substantial methemoglobinemia (less than 2%). The bronchodilating effects of NO were additive with the effects of inhaled terbutaline, irrespective of the sequence of NO and terbutaline administration. Inhaling aerosol generated from S-nitroso-N-acetylpenicillamine also induced a rapid and profound decrease of RL from 0.453 +/- 0.022 to 0.287 +/- 0.022 cmH2O/ml.s, which lasted for over 15 min in guinea pigs broncho-constricted with methacholine. Our results indicate that low levels of inhaled gaseous NO, or an aerosolized NO-releasing compound are potent bronchodilators in guinea pigs.