Reduced exhaled NO is related to impaired nasal potential difference in patients with cystic fibrosis.

Nitric oxide (NO) plays a central role in many airway physiological functions, and its production appears to be related with progression of lung disease in patients with cystic fibrosis (CF). However, underlying mechanisms which specifically link NO and CF-related lung disease remain unclear. Following in vitro and animal studies suggesting a role for NO in ion transport in various epithelia, this work investigates the relationship between transepithelial baseline potential difference (BPD), an index of airway ion transport, and exhaled NO in the airways of adult patients with CF. Association with other phenotypic traits, lung function tests and CFTR genotype was also assessed. Using simple linear regression, F(E)NO and transepithelial BPD values were significantly inversely correlated (p<0.001, r=-0.53). Polynomial analysis evidenced an asymptotic relationship between F(E)NO and BPD values, yielding a plateau for absolute BPD values above 50 mV. This relation was not altered by adjustment for clinical and genetic characteristics of the patients. The relationship between exhaled NO and transepithelial BPD suggests that low NO concentrations likely worsens airway ion transport impairment resulting from CFTR defect. These results fit with experimental studies that suggest the inhibitory effect of NO on sodium absorption, which is the main determinant of airway basal transepithelial conductance.

Nasal airway ion transport is linked to the cystic fibrosis phenotype in adult patients.

BACKGROUND: This study was conducted to determine whether the major nasal airway ion transport abnormalities in cystic fibrosis (that is, defective cAMP regulated chloride secretion and basal sodium hyperabsorption) are related to the clinical expression of cystic fibrosis and/or to the genotype. METHODS: Nasal potential difference was measured in 79 adult patients with cystic fibrosis for whom clinical status, respiratory function, and CFTR genotype were determined. RESULTS: In univariate and multivariate analysis, patients with pancreatic insufficiency were more likely to have low responses to low chloride (odds ratio (OR) 8.6 (95% CI 1.3 to 58.5), p = 0.03) and isoproterenol (OR 11.2 (95% CI 1.3 to 93.9), p = 0.03) solutions. Similarly, in univariate and multivariate analysis, patients with poor respiratory function (forced expiratory volume in 1 second <50% of predicted value) were more likely to have an enhanced response to amiloride solution (OR 3.7 (95% CI 1.3 to 11.0), p = 0.02). However, there was no significant relationship between nasal potential difference and the severity of the genotype. CONCLUSIONS: Nasal epithelial ion transport in cystic fibrosis is linked to the clinical expression of the disease. The pancreatic status appears to be mostly related to the defect in epithelial chloride secretion whereas the respiratory status is mostly related to abnormal sodium transport and the regulatory function of the CFTR protein.

Nitric oxide synthase 1 as a potential modifier gene of decline in lung function in patients with cystic fibrosis.

BACKGROUND: The severity of lung disease varies widely in patients with cystic fibrosis (CF) who have the same type of mutations of the cystic fibrosis transmembrane regulator (CFTR) gene, suggesting involvement of "modifier" genes. The nitric oxide synthase 1 (NOS1) gene is a candidate for this role because exhaled nitric oxide (NO) is reduced in patients with CF and NOS1 activity contributes to transepithelial ionic transport, immune defence, and non-specific inflammation of the airways. METHODS: Dinucleotide GT repeat polymorphism was studied in the 5' untranslated region of the NOS1 gene, immediately upstream from the transcription initiation site, in 59 patients with CF and 59 healthy controls. RESULTS: Nineteen alleles of the NOS1 gene were identified according to the number of GT repeats (from 18 to 36) in the 5 untranslated region. Exhaled NO levels were significantly correlated with the number of GT repeats. Patients with CF who had the NOS1 genotype associated with high NO production had a slower decline in lung function during the 5 year follow up period. There was no confounding effect of age, chronic bacterial colonisation of the airway, or CFTR genotype. CONCLUSIONS: These data suggest a possible link between the NOS1 gene locus and the rate of decline in lung function in patients with CF.

Exhaled and nasal nitric oxide as a marker of pneumonia in ventilated patients.

Because inflammation stimulates the expression of inducible nitric oxide (NO) synthase (iNOS) with an associated increased local NO production, we hypothesized that patients with pneumonia would have increased excretion of NO into their airways. To test this hypothesis, NO was measured in the exhaled air and from the nasal cavities of 49 consecutively intubated and mechanically ventilated patients in our ICU. After excluding NO gas contamination in the inspiratory circuit, nasal NO and end-expiratory and mean exhaled tracheal NO levels and plasma nitrate concentrations were measured using a fast response chemiluminescence analyzer. Twenty-one patients (43%) presented with infectious pneumonia. End- expiratory exhaled NO concentrations were significantly higher in patients with pneumonia as compared with patients without pneumonia (5.9 +/- 1 ppb versus 3.2 +/- 0.5 ppb, p < 0.01). Similarly, mean nasal NO was higher in patients with pneumonia (1039 +/- 138 ppb versus 367 +/- 58 ppb, p = 0.003). Plasma nitrate levels did not differ between patient groups. Threshold values of tracheal or nasal NO were defined and subsequently validated in 60 other patients. Positive and negative values of a maximal tracheal level > 5 ppb for pneumonia were 74% and 89%, respectively. Thus tracheal and nasal NO levels may be of help in distinguishing patients with acute pneumonia from other causes. Furthermore, because these differences in airway NO levels were not paralleled in blood nitrite concentrations, we conclude that pneumonia per se is not associated with systemic NO production.

Association of PEEP with two different inflation volumes in ARDS patients: effects on passive lung deflation and alveolar recruitment.

OBJECTIVE: To assess the effects of the association of positive end-expiratory pressure (PEEP) with different inflation volumes (V(T)'s) on passive lung deflation and alveolar recruitment in ARDS patients. DESIGN: Clinical study using PEEP with two different V(T)'s and analyzing whether passive lung deflation and alveolar recruitment (Vrec) depend on end-inspired (EILV) or end-expired (EELV) lung volume in mechanically ventilated ARDS patients. SETTING: Medical intensive care unit in a university hospital. PATIENTS AND PARTICIPANTS: Six mechanically ventilated consecutive supine patients with ARDS. INTERVENTIONS: Time-course of thoracic volume decay during passive expiration and Vrec were investigated in six ARDS patients ventilated on PEEP with baseline V(T) (V(T),b) and 0.5V(T) (0.5V(T),b), and on zero PEEP (ZEEP) with V(T),b. Time constants of the fast (tau1) and slow (tau2) emptying compartments, as well as resistances and elastances were also determined. MEASUREMENTS AND RESULTS: (a) the biexponential model best fitted the volume decay in all instances. The fast compartment was responsible for 84+/-7 (0.5V(T),b) and 86+/-5% (V(T),b) on PEEP vs 81+/-6% (V(T),b) on ZEEP (P:ns) of the exhaled V(T), with tau1 of 0.50+/-0.13 and 0.58+/-0.17 s vs 0.35+/-0.11 s, respectively; (b) only tau1 for V(T),b on PEEP differed significantly (P < 0.02) from the one on ZEEP, suggesting a slower initial emptying; (c) for the same PEEP, Vrec was higher with a higher volume (V(T)b) than at a lesser one (0.5V(T),b), reflecting the higher V(T). CONCLUSIONS: In mechanically ventilated ARDS patients: (a) the behavior of airway resistance seems to depend on the degree of the prevailing lung distension; (b) alveolar recruitment appears to be more important when higher tidal volumes are used during mechanical ventilation on PEEP; (c) PEEP changes the mechanical properties of the respiratory system fast-emptying compartment.

Maturational changes of endothelial vasoactive factors and pulmonary vascular tone at birth.

The aim of this study was to determine which endothelial factors were involved in the decrease of pulmonary vascular resistance at birth, and how they changed with maturation. Response of intrapulmonary artery rings precontracted with prostaglandin F2alpha were studied from piglets aged <2 h, 2-3 day, 10 day and adult pigs for pharmacological responses to acetylcholine (ACh) and cromakalim (CMK) in the presence and the absence of the nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine (L-NA), the adenosine triphosphate sensitive potassium (K(ATP)) channel blocker, glibenclamide and the endothelin (ET)-A receptor antagonist, BQ123. In situ hybridization and immunochemistry studies were performed in lung tissues of the same animals in order to determine the expression of NOS and ET. There was a small contractile effect of ACh in the newborn. Relaxation to ACh, which was blocked by L-NA and reduced by glibenclamide, only appeared from the age of 3 days. The significantly greater relaxation to CMK in rings without endothelium (p<0.05) was abolished by BQ123 in the newborn, and then disappeared by 2 days of age. Glibenclamide had a greater inhibitory effect on relaxation induced by CMK at 10 days than in the newborn and 2 days old piglets. NOS expression was low in pulmonary arteries of the newborn and increased by 2 days of age whereas the converse was seen with ET expression. It is concluded that: 1) relaxant response to acetylcholine was absent at birth and appeared at 2 days; 2) the reduced relaxant response to cromakalin in rings with endothelium at birth could be blocked by BQ123; and 3) the expression of endothelin decreased whereas the expression of nitric oxide synthase increased from birth to 2 days of age.

[In vitro study of the modulation of human ureteral tonus by nitric oxide and zaprinast, a phosphodiesterase inhibitor]. / Etude in vitro de la modulation du tonus urétéral humain par le monoxyde d'azote et un inhibiteur des phosphodiestérases, le zaprinast.

AIM OF THE STUDY: To assess the role of nitric oxide (NO) and its second messenger, cGMP, on the mechanisms underlying human ureteral smooth muscle relaxation. METHODS: Proximal segments of ureter were dissected from nephrectomy, then cut into rings and suspended in organ chambers. Isometric tone was recorded at baseline and after preincubation with KCl (120 mumol). The Increasing concentration (10-8-10-4 M) of NO donors, Sodium nitroprusside, (SNP) and molsidomine (SIN-1) and a type V phosphodiesterase inhibitor, Zaprinast were added to the organ chambers and a dose response curve was constructed from each experiment. RESULTS: Dose-dependent relaxation was seen with all compounds. This was, however, more pronounced with SNP as compared with SIN-1. Zaprinast alone had marginal relaxant effect but markedly potentiated the relaxing effect of the NO donor SNP (p < 0.05). Inhibition of NO synthesis by the arginine analogue L-NA increased electrical-induced contraction (98 +/- 4% vs 122 +/- 3%, p < 0.001). CONCLUSION: Activation of the soluble guanylate cyclase by NO donors markedly relaxed significantly human ureteral smooth muscle but inhibition of phosphodiesterase did not affect the in vitro relaxation. Our results suggest that cGMP is an important second messenger in the transduction signalling pathway leading to relaxation of human ureteral smooth muscle. By contrast, basal activity of phosphodiesterase seems to be marginal under physiological condition.

Nitric oxide deficiency in fenfluramine- and dexfenfluramine-induced pulmonary hypertension.

Dexfenfluramine and fenfluramine greatly increase the risk of developing pulmonary hypertension (PHT). The mechanism of anorexigen-associated PHT (AA-PHT) and the reason PHT occurs in a minority of people exposed are unknown. Anorexigens are weak pulmonary vasoconstrictors, but they become potent when synthesis of the endogenous vasodilator nitric oxide (NO) is suppressed. We hypothesized NO deficiency predisposes affected individuals to develop AA-PHT. A prospective, case-control, study was performed on consecutive patients with AA-PHT (n = 9). Two sex-matched control groups were selected: patients with primary PHT (P-PHT, n = 8) and normal volunteers (n = 12). Lung NO production (VNO) and systemic plasma oxidation products of NO (NOx) were measured at rest and during exercise. AA-PHT developed 17 +/- 6 mo after a short course of anorexigen (6 +/- 2 mo) and was irreversible. VNO was lower in AA-PHT than in P-PHT and correlated inversely with PVR (p < 0.05). The apparent VNO deficiency may have resulted from increased oxidative inactivation of NO in patients with AA-PHT, as their NOx levels were elevated (p < 0.05) in inverse proportion to VNO (r2 = 0. 55; p < 0.02). In susceptible persons, anorexigens can cause an irreversible syndrome of PHT, hypoxemia, and systemic vascular complications after brief exposures. These patients have a relative NO deficiency years after discontinuing the anorexigen, perhaps explaining their original susceptibility.

Increased nitric oxide in exhaled air in patients with systemic sclerosis.

OBJECTIVE: To assess the lung production of nitric oxide (NO) in patients with systemic sclerosis. METHODS: The NO concentration and its rate of production by the lungs were measured in the exhaled air in 14 patients with systemic sclerosis and in 12 healthy control subjects using the chemiluminescent method. RESULTS: The NO concentration and its rate of production were significantly increased in scleroderma patients (mean +/- SEM, 18.7 +/- 1.7 ppb and 5.8 +/- 0.5 nmol/min, respectively), as compared with control subjects (11.2 +/- 0.8 ppb and 4.3 +/- 0.4 nmol/min, p < 0.01 and p < 0.05, respectively). CONCLUSION: The pulmonary production of NO is increased in scleroderma patients, which might reflect and contribute to the inflammatory processes of the lungs in systemic sclerosis.

Blood gas measurement during exercise: a comparative study between arterialized earlobe sampling and direct arterial puncture in adults.

Sampling arterialized earlobe blood is thought to be easier and less painful than direct arterial puncture, and to allow measurement of blood gas values during exercise without the need to insert an arterial cannula. However, arterialized earlobe oxygen tension (PO2) often underestimates arterial PO2 at rest, and is not fully validated during exercise. We have therefore conducted a prospective study to compare values of PO2 and carbon dioxide tension (PCO2) and the discomfort experienced by adult subjects undergoing the two methods of blood sampling during exercise. Seventy consecutive adult patients were studied. Blood samples were drawn simultaneously from the radial artery and arterialized earlobe of each patient during the last minute of an 8 min exercise. Values of PO2 and PCO2 were measured by means of blood gas electrodes. The correlation coefficients between the two samples were 0.92 for PO2 and 0.91 for PCO2. However, the bias and the limits of agreement between the two methods were wide for PO2 (mean+/-2SD of the differences between the two methods: 0.63+/-1.50 kPa (4.7+/-11.2 mmHg)). The bias and the limits of agreement were smaller for PCO2. Patients felt that the earlobe method was not associated with less discomfort than radial artery puncture. We conclude that arterialized earlobe blood oxygen tension is not a good substitute for arterial oxygen tension during exercise, and should not be used to assess arterial oxygen tension in adults during exercise.

Effects of muscimol or homotaurine on sleep-wake states in alcohol-dependent rats during withdrawal.

Sleep-wake states were studied following withdrawal in 36 adult male wistar alcohol-dependent rats, after chronic administration of ethanol (10 g/kg/24 h) for 13 days. In the light phase of the withdrawal day, 12 alcohol-dependent rats received muscimol (0.25 mg/kg), 12 received homotaurine (140 mg/kg), and 12 received 0.9% physiological saline (10 ml/kg). The results have been compared with a control group of 36 rats that received water during the treatment phase of the experiment, and the 14th day received intraperitoneal muscimol or homotaurine. Muscimol significantly improves the alterations of sleep-wake states in alcohol-withdrawn rats, decreasing the percentage of active wakefulness and increasing the percentage of REMS, but without any action on the latency of appearance of REMS, which remains shortened. The effects of homotaurine are less important on the wakefulness, but it also increases the percentage of REMS without influencing its latency of appearance. The influence of these GABA(A) agonists is not identical during the whole period of survey in the light phase, as there are important differences in the temporal sequences for each of them. We conclude that the stimulation of GABA(A) receptors, of which the activity is decreased during alcohol withdrawal, significantly improves the disturbances in the sleep-wake states in the alcohol-dependent rats, in a time-related manner, and there are significant pharmacodynamic differences between muscimol and homotaurine.

Relationships between nasal potential difference and respiratory function in adults with cystic fibrosis.

This study investigated the relations between nasal transepithelial electric potential difference (PD) and the phenotype and genotype of cystic fibrosis (CF) adult patients. Basal nasal PD was measured in 95 adult CF patients who were classified into three groups of nasal PD (expressed as absolute values) according to the 10th and the 90th percentiles (28.3 and 49.2 mV, respectively), which defined group 1 (nasal PD < or =28.3 mV), group 2 (nasal PD 28.3-49.2 mV) and group 3 (nasal PD > or =49.2 mV). Patients from group 1 had a higher forced vital capacity (FVC) than patients from groups 2 and 3 (76.5+/-22.4 versus 57.4+/-21.2 and 55.7+/-21.1% predicted, respectively, p<0.05) and a higher forced expiratory volume in one second (FEV1) (69.3+/-24.0 versus 42.5+/-22.4 and 42.2+/-21.4% pred, respectively, p<0.01). Among patients with severe mutations (deltaF508 homozygotes, or one deltaF508 mutation plus another "severe" mutation, or two "severe" mutations), patients from group 1 had a higher FVC, FEV1 and arterial oxygen tension than patients from groups 2 and 3 (p<0.05 for each comparison). The results show that in adult cystic fibrosis patients a normal basal nasal potential difference is related to milder respiratory disease, irrespective of the severity of the genotype.

Silver/silver chloride electrodes for measurement of potential difference in human bronchi.

BACKGROUND: An easy and reliable method to measure potential difference (PD) in the lower airways would be of interest in the field of cystic fibrosis. We have developed silver/silver chloride (Ag/AgCl) electrodes to measure PD in the lower airways. METHODS: To validate this technique the nasal PD measured with Ag/AgCl electrodes and with conventional perfused electrodes was compared in 16 patients. The range of PD measured with Ag/AgCl electrodes in the lower airways during fibreoptic bronchoscopy was determined in 14 adult patients and in nine the reproducibility of this technique was examined. RESULTS: Nasal PD values measured with Ag/AgCl and perfused electrodes were highly correlated (r = 0.985, p < 0.0001) and the limits of agreement (mean +/- 2SD of the difference) between the two methods were -1.91 mV and 1.53 mV. In the lower airways a progressive and slight decrease in PD values with decreasing airway diameter was observed in most patients. The mean (2SD) of the differences between the two tracheal measurements was 0.21 (1.73) mV. CONCLUSIONS: The use of Ag/AgCl electrodes gives a reliable and reproducible measurement of PD in the lower airways in humans.

Comparison of transesophageal echocardiographic, fick, and thermodilution cardiac output in critically ill patients.

PURPOSE: Recent observations have highlighted errors in the thermodilution technique of measuring cardiac output. Thus, cardiac output measurements using transesophageal echocardiography and the Fick method were compared with simultaneous thermodilution measurements. METHODS: In 13 mechanically ventilated critically ill patients, cardiac output was determined simultaneously using (1) transesophageal echocardiography (COTEE, (2) the Fick method (COFICK, and (3) thermodilution (COTD immediately before and after a rapid infusion of 500 mL of saline. Left ventricular end-diastolic and end-systolic areas were measured using the transesophageal echocardiographic transgastric short axis view, and COTEE was calculated from the corresponding volumes. Absolute cardiac output values and the changes from before to after saline infusion (delta CO) were compared using analysis of variance, linear regression, and the Bland and Altman method. RESULTS: There were no significant differences between COTEE (8.0 +/- 3.4), COFICK (8.4 +/- 3.3), and COTD (8.3 +/- 3.0) or between delta COTEE, delta COFICK, and delta COTD using analysis of variance. However, correlations between COTEE and COTD (r2 = 0.46; P < .00001), COFICK and COTD (r2 = 0.46; P < .0001), and COTEE and COFICK (r2 = 0.42; P < .0001) were only moderately good. Using the method of Bland and Altman, the mean difference (+/-2 standard deviations) between COTEE and COTD was 0.3 +/- 4.3 L/min, between COFICK and COTD was -1.0 +/- 3.8 L/min, and between COTEE and COFICK was 0.6 +/- 5.6 L/min, whereas the difference between delta COTEE and delta COTD was 0% +/- 26%, between delta COFICK and delta COTD was 9% +/- 46%, and between delta COTEE and delta COFICK was 8% +/- 39%. CONCLUSIONS: There are substantial differences in cardiac output as measured by these three methods, best demonstrated using the method of Bland and Altman. The variability of cardiac output and its derivatives (eg, oxygen delivery) should be borne in mind when making clinical decisions on individual patients.

Exhaled nitric oxide during acute changes of airways calibre in asthma.

It has been shown that endogenous nitric oxide (NO), measured in exhaled air, is increased in asthmatic subjects and after allergen challenge in sensitized animals. NO is also a paracrine molecule with some, though weak, bronchodilator effects. However, whether the amount of endogenous NO that originates in the lungs can reflect the degree of bronchial tone and airways calibre in asthmatic subjects has not yet been investigated. The aim of this study was, therefore, to determine whether NO production could be modified by acute changes of airways calibre in mild, nonatopic, asthmatic subjects. NO output was measured in the exhaled air of 14 steroid-free asthmatics, 8 steroid-treated asthmatics and 21 control subjects. In seven steroid-free asthmatics, exhaled NO was measured after methacholine challenge, and then after salbutamol-induced bronchial dilatation. Exhaled tidal breathing was collected for 30 s and NO in the exhaled air was measured with a chemiluminescence analyser. Both NO concentration and its output were significantly higher in the steroid-free asthmatic patients (15.6 +/- 1.5 parts per billion (ppb) and 6.3 +/- 0.7 nmol.min-1, respectively) as compared with the control subjects (8.9 +/- 1.0 ppb and 3.5 +/- 0.3 nmol.min-1, respectively; p < 0.001 for both) and with the steroid-treated asthmatic patients (11.3 +/- 3.3 ppb and 3.7 +/- 0.9 nmol.min-1, respectively; p < 0.05 for both). Neither methacholine-induced bronchial obstruction nor salbutamol-induced bronchial dilatation caused a significant change in exhaled NO. We conclude that NO production is higher in steroid-free than in steroid-treated asthmatics and in control subjects. Furthermore, NO production is not affected by acute pharmacologically-induced changes of airways calibre in asthmatic subjects. Our results suggest that NO production is a marker of airways inflammation rather than an endogenous modulator of bronchial tone in asthma.

Role of NO in the pulmonary artery hyporeactivity to phenylephrine in experimental biliary cirrhosis.

The aim of this study was to see whether increased activity of nitric oxide (NO) might account for decreased pulmonary vascular tone seen in the hyperdynamic circulation of cirrhosis. We compared the pulmonary vascular reactivity of isolated pulmonary arteries (PA) from control rats (n = 10), and rats with biliary cirrhosis (n = 10) induced by chronic bile duct ligation (4 weeks). The responses of PA rings to cumulative concentrations of phenylephrine, acetylcholine, and sodium nitroprusside were studied, and also the effects of inhibition of synthesis of NO by the L-arginine analogue, N omega-nitro-L-arginine (L-NOARG) in PA rings challenged with cumulative concentrations of phenylephrine and acetylcholine. The contractile response to phenylephrine was significantly reduced in cirrhotic PA rings as compared with controls. Pretreatment with L-NOARG (10(-4) M) significantly increased the contractile response to phenylephrine in PA rings from cirrhotic rats but not in control PA rings. Furthermore, L-NOARG restored the response to phenylephrine in cirrhotic PA rings back to normal. There was no difference in the relaxation of PA rings from both groups in response to acetylcholine and sodium nitroprusside. We conclude that in vitro pulmonary artery ring hyporeactivity to phenylephrine results from increased nitric oxide production in the pulmonary circulation of cirrhotic rats and might account for the hepatopulmonary syndrome.

Endogenous pulmonary nitric oxide production measured from exhaled air is increased in patients with severe cirrhosis.

BACKGROUND/AIMS: Endogenous pulmonary nitric oxide production may be increased in severe cirrhosis and contribute to pulmonary vasodilation. This study assessed pulmonary nitric oxide production by measuring nitric oxide in the exhaled air in patients with severe cirrhosis and examined the relationship between exhaled nitric oxide and pulmonary hemodynamics in these patients. METHODS: Nitric oxide concentrations and production were measured in the exhaled air in six Child-Pugh class C patients with cirrhosis and 21 non-smoking healthy controls. Systemic and pulmonary hemodynamics were measured in patients only. RESULTS: Nitric oxide concentration (32.0 +/- 1.7 (mean +/- SEM) vs. 8.9 +/- 1.0 ppb) and production (9.2 +/- 1.3 vs. 3.1 +/- 0.3 nmol/min) in exhaled air were significantly higher in patients than in controls. Patients had high cardiac output (8.5 +/- 0.9 l/min), low pulmonary and systemic vascular resistance (57 +/- 10 and 767 +/- 93 dyn.s.cm-5, respectively) under baseline conditions. A significant negative correlation was found between pulmonary vascular resistance and exhaled nitric oxide production (r=0.943, p=0.05) but not between cardiac output or systemic vascular resistance and nitric oxide measured in exhaled air. CONCLUSIONS: Endogenous pulmonary nitric oxide production measured from exhaled air is increased in patients with cirrhosis and liver failure. Increased in patients with cirrhosis and liver failure. Increased nitric oxide production may also contribute to cirrhosis-induced pulmonary vasodilatation.

Effect of inhaled nitric oxide on right ventricular function in adult respiratory distress syndrome.

To determine whether inhaled nitric oxide (NO) affects pulmonary circulation, thereby improving right ventricular (RV) function in adult respiratory distress syndrome (ARDS), we studied 13 patients with both a lung injury severity score of 2.5 or more and a mean pulmonary artery pressure higher than 30 mm Hg. RV function was assessed by a thermodilution technique using a pulmonary artery catheter equipped with a rapid response thermistor before and 15 min after initiation of inhalation of NO (5 ppm). At baseline, stroke volumes were in a normal range (46 +/- 14 ml/m2), with a RV dilation (end-diastolic volume = 142 +/- 36 ml/m2). Inhaled NO was followed by an improvement in arterial oxygenation (PaO2/FIO2 = 103 +/- 47 versus 142 +/- 63, p < 0.05) and a drop in pulmonary artery pressure (36.1 +/- 4.5 versus 31.3 +/- 6.1 mm Hg, p < 0.01); stroke volumes and heart rates did not change. The resulting fall in pulmonary vascular resistance (211 +/- 43 versus 180 +/- 59 dyn-s/cm5, p < 0.05) was associated with an increase in RV, ejection fractions (32 +/- 5 versus 36 +/- 6%, p < 0.05), a trend toward decreased RV end-systolic (96 +/- 25 versus 85 +/- 19 ml/m2, NS) and end-diastolic (142 +/- 36 versus 131 +/- 27 ml/m2, NS) volumes, and a decrease in right atrial pressures (10.9 +/- 2.9 versus 9.6 +/- 3.2 mm Hg, p < 0.05). No relationship was seen between the improvement in arterial oxygenation and the decrease in pulmonary vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)