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PubMed2000

Regular inhaled salbutamol and asthma control: the TRUST randomised trial. Therapy Working Group of the National Asthma Task Force and the MRC General Practice Research Framework.

BACKGROUND: Previous work has suggested that the long-term regular use of inhaled beta2-agonist bronchodilators might lead to a deterioration in asthma control. The aim of TRUST (The Regular Use of Salbutamol Trial) was to study the effects of regular use of inhaled salbutamol, the most widely prescribed bronchodilator in the UK, on the control of asthma. METHODS: A randomised, double-blind, placebo-controlled trial was undertaken in 983 patients with asthma being treated at least twice a week with short-acting beta2-agonist, alone or in combination with inhaled steroids (2 mg or less) daily. Patients were aged 18 years and over and were recruited from 115 general practices in the UK. 90% (881) of the patients used inhaled corticosteroid therapy, and all patients continued to use their usual inhaled beta2-agonist for symptomatic relief. Patients were randomised to receive 400 microg salbutamol or matched placebo via a Diskhaler four times per day for 12 months. The primary outcome measure was rate of exacerbations of asthma, with criteria based on data from diary cards completed daily by each patient, treatment with additional corticosteroids, or both. FINDINGS: There were no differences in the annual rate, timing, or duration of exacerbations between the two groups. The mean morning peak expiratory flow was similar for the two groups. The mean evening peak expiratory flow (p<0.001) and the diurnal variation (p<0.001) were greater, and the use of rescue bronchodilator was less (p<0.001), in the group receiving regular salbutamol. INTERPRETATION: There was no evidence that regular use of inhaled salbutamol 400 microg four times daily for a year increased the exacerbation rate of asthma in the population studied.

Administration, Inhalation↗
PubMed2000

Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study.

BACKGROUND: Inhaled corticosteroids are currently the cornerstone of asthma treatment. Some studies of high-dose fluticasone propionate in patients with no or mild asthma have, however, suggested substantial systemic absorption. We investigated the pharmacokinetics of fluticasone propionate in patients with asthma receiving appropriate doses for severity. METHODS: We did a double-blind, randomised, crossover study in 11 patients with asthma and 13 matched healthy controls (age 20-65 years; asthma patients forced expiratory volume in 1 s <75% and stable on high-dose inhaled corticosteroids). Patients received one 1000 microg intravenous dose or 1000 microg daily for 7 days inhaled (via spacer device) fluticasone propionate. In the 12 h after dosing, we monitored plasma fluticasone propionate and cortisol concentrations by mass spectrometry and competitive immunoassay with use of direct chemiluminescence. Analysis was by intention to treat. FINDINGS: After inhalation, geometric mean values were significantly lower in the asthma group than in controls for fluticasone propionate plasma area under curve (1082 [95% CI 850-1451] vs 2815 pg mL(-1) h(-1) [2262-3949], -62% difference [45-72]; p<0.001), maximum concentrations (117 [91-159] vs 383 pg/mL [302-546], -68% [-50 to -81]; p<0.001), and systemic bioavailability (10.1 [7.9-14.0] vs 21.4% [15.4-32.2], -54% [-27 to -70]; p=0.001). Intravenous-dose clearance, volume of distribution at steady state, plasma half-life, and mean residence time, were similar in the two groups. Less suppression of plasma cortisol concentrations was seen in the asthma group than in controls 4-12 h after inhaled fluticasone propionate. INTERPRETATION: Systemic availability of fluticasone propionate is substantially less in patients with moderate to severe asthma than in healthy controls. Inhaled corticosteroids that are absorbed through the lungs need to be assessed in patients who are receiving doses appropriate for disease severity, and not in normal volunteers.

Administration, Inhalation↗
PubMed1997

Randomised placebo-controlled trial of inhaled sodium cromoglycate in 1-4-year-old children with moderate asthma.

BACKGROUND: Inhalation therapy with sodium cromoglycate is recommended as the first-line prophylactic treatment for moderate asthma in children. The availability of spacer devices with face-masks has extended the applicability of metered-dose inhalers to younger children. We studied the feasibility and effects of this therapy compared with placebo in children aged 1-4 years. METHODS: 218 children aged 1-4 years with moderate asthma were recruited through 151 general practitioners between March, 1995, and March, 1996. They were randomly assigned sodium cromoglycate (10 mg three times daily) or placebo, given by inhaler with spacer device and face-mask for 5 months. Rescue medication (ipratropium plus fenoterol aerosol) was available during the baseline period of 1 month and the intervention period. Parents completed a daily symptom-score list. The primary outcome measure was the proportion of symptom-free days in months 2 to 5. Analysis was by both intention to treat and on treatment. FINDINGS: 167 (77%) children completed the trial. 131 (78%) of these children used at least 80% of the recommended dose. Of the 51 children who stopped prematurely, 23 had difficulties with inhaled treatment. The mean proportion of symptom-free days for both groups was greater for the treatment period than for the baseline period (95% CI for mean difference 5.1 to 17.5 cromoglycate, 11.9 to 23.3 placebo). However there were no differences between the sodium cromoglycate and placebo groups in the proportion of symptom-free days (mean 65.7 [SD 25.3] vs 64.3 [24.5]%; 95% CI for difference -8.46 to 5.70) or in any other outcome measure. INTERPRETATION: Our study in a general practice setting shows that inhalation therapy with a spacer device and face-mask is feasible in a majority of children below the age of 4 years. However, long-term prophylactic therapy with inhaled sodium cromoglycate is not more effective than placebo in this age-group.

Administration, Inhalation↗
PubMed1999

Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial.

BACKGROUND: Little is known about the long-term efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). We investigated the efficacy of inhaled budesonide on decline in lung function and respiratory symptoms in a 3-year placebo-controlled study of patients with COPD. METHODS: We used a parallel-group, randomised, double-blind, placebo-controlled design in a singlecentre study, nested in a continuing epidemiological survey (the Copenhagen City Heart Study). Inclusion criteria were as follows: no asthma; a ratio of forced expiratory volume in 1 s (FEV1) and vital capacity of 0.7 or less; FEV1 which showed no response (<15% change) to 1 mg inhaled terbutaline or prednisolone 37.5 mg orally once daily for 10 days. 290 patients were randomly assigned budesonide, 800 microg plus 400 microg daily for 6 months followed by 400 microg twice daily for 30 months, or placebo for 36 months. The mean age of the participants was 59 years and the mean FEV1 2.37 L or 86% of predicted. The main outcome measure was rate of FEV1 decline. Analyses were by intention to treat. FINDINGS: The crude rates of FEV1 decline were slightly smaller than expected (placebo group 41.8 mL per year, budesonide group 45.1 mL per year). The estimated rates of decline from the regression model did not differ significantly (49.1 mL vs 46.0 mL per year; difference 3.1 mL per year [95% CI -12.8 to 19.0]; p=0.7). Before the study, the minimum relevant difference was defined as 20 mL per year; this difference was outside the 95% CI. No effect of inhaled budesonide was seen on respiratory symptoms. 316 exacerbations occurred during the study period, 155 in the budesonide group and 161 in the placebo group. Treatment was well tolerated. INTERPRETATION: Inhaled budesonide was of no clinical benefit in COPD patients recruited from the general population by screening. We question the role of long-term inhaled corticosteroids in the treatment of mild to moderate COPD.

Administration, Inhalation↗
PubMed2000

Use of hydrofluoroalkane propellant delivery system for inhaled albuterol in patients receiving asthma medications.

OBJECTIVE: This study was undertaken to assess drug-use patterns associated with albuterol delivery via a new propellant device compared with conventional chlorofluorocarbon (CFC) metered-dose inhalers (MDIs) in patients taking asthma medications in a population with pharmacy benefits. BACKGROUND: In addition to their ozone-depleting properties, conventional CFC inhalers often deliver inconsistent doses because of loss of prime and temperature instability. A new propellant, hydrofluoroalkane (HFA), incorporates a re-engineered delivery system associated with dosing reproducibility throughout the life of the canister. METHODS: Drug markers associated with management of asthma were used to identify a study cohort of new users of inhaled albuterol from a geographically diverse pharmacyclaims database from July 1, 1997, through December 31, 1997. A population of 282,879 members was identified over the 20-month follow-up period. In addition, a subset of chronic albuterol inhaler users (> or = 12 months; n = 96,879) was also identified to support a longitudinal analysis. Disease severity was controlled for by use of inhaled corticosteroids (ICS). To control for canisters received via physician office samples, HFA patient use was corrected by a physician-based canister adjustment based on HFA sample data. RESULTS: A total of 53.1% of participants were women and 46.1% were men; most of the population (72.5%) was <65 years of age. Canister use for HFA patients was consistently lower (2.7+/-3.2 vs 5.4+/-6.7) than for CFC MDIs for the entire cohort over the 20-month assessment period. This difference was consistently observed for albuterol canister use in patients with and without concomitant ICS use (3.3+/-3.8 HFA vs 7.2+/-7.5 CFC for ICS users and 2.1+/-2.1 HFA vs 4.1+/-5.7 CFC for non-ICS users). Time to next prescription also was longer for HFA patients than for CFC patients (61.6+/-50.9 days HFA vs 47.3+/-40.8 days CFC). When duration of therapy and physician samples associated with product launch were controlled for, similar differences were consistently observed. CFC patients used, on average, 1.3 more canisters per year than did HFA patients (P < 0.001), averaging 10.7 canisters (95% CI, 10.6 to 10.7), compared with 9.4 canisters used by HFA patients (95% CI, 8.9 to 9.9). Further analyses indicated that this finding was consistent when ICS use was controlled for (CFC plus ICS mean, 11.9 canisters vs HFA plus ICS mean, 10.4 canisters; P < 0.001). CONCLUSION: This study provides useful information about the effect of use of a new albuterol delivery system on asthma inhaler management. These data suggest that CFC patients use an average of 1.3 more canisters per year compared with HFA patients independent of asthma severity as measured by ICS use. This improvement in dosing characteristics has the potential to translate into enhanced economic outcomes.

Administration, Inhalation↗
PubMed1997

Central serous chorioretinopathy associated with inhaled or intranasal corticosteroids.

OBJECTIVE: The purpose of the study is to investigate the relationship between inhaled or intranasal adrenergic agonists and corticosteroids and the development of central serous chorioretinopathy (CSC). DESIGN: The medical records of three patients with CSC who were found to use inhaled adrenergic agents or corticosteroids or both were identified prospectively. A survey of members of the Retina, Macula, and Vitreous societies and the National Registry of Drug-Induced Ocular Side Effects identified three additional cases. RESULTS: Six patients with CSC were found to be chronic users of corticosteroid (four patients) or both beta adrenergic agonist and corticosteroid (two patients) metered dose inhalers or nasal sprays. In three cases, there was a close temporal correlation between the use of a corticosteroid nasal spray and the development of CSC. CONCLUSIONS: These findings suggest that, in patients who are susceptible, the periocular or systemic absorption of inhaled corticosteroids may be sufficient to produce CSC in humans, supporting previous hypotheses regarding the pathogenesis of the disorder. Further studies are needed to confirm this association and to determine whether inhaled adrenergic agents also contribute to the development of this disorder. Patients in whom CSC develops while using corticosteroid inhalers or nasal sprays should be alerted to the possible relationship between CSC and these agents.

Administration, Inhalation↗
PubMed2003

Inhalation therapy: technological milestones in asthma treatment.

The humble origins of the propellant driven metered dose inhaler, as a response to a child's enquiry, initiated an industry which supplies approximately a half billion inhalers globally for the treatment of asthma. These inhalers fall into three major groups: nebulizers; propellant driven metered dose inhalers and dry powder inhalers. Each requires drug formulation, metering and device technology to be successful. In recent years there have been several new developments in the field including auxiliary systems to improve drug delivery from the device to the patient and new categories of device, notably single breath aqueous systems. As device technology improves and our understanding of the disease leads to new drugs the only barrier to therapy is the patient. Patient training and compliance will continue to be important factors in the success, or failure, of inhaled therapy and the role of health care professionals will depend on who sponsors their intervention.

Administration, Inhalation↗
PubMed1998

The role of inhalation rewarming in the early management of hypothermia.

OBJECTIVE: To evaluate the effectiveness of inhalation rewarming in early resuscitative efforts for hypothermic victims. DATA SOURCES: Search of MEDLINE and manual retrieval using the terms hypothermia, resuscitation, inhalation and treatment. All articles and papers published within the last 5 years were searched. Earlier literature was also included if considered vital to documenting the scientific basis and rationale for using airway rewarming. STUDY SELECTION: Letters to the editor, review articles, case reports and original research were included in this review. Material was considered for inclusion if it contributed generally to the understanding of the role of inhalation rewarming in the stabilization or treatment of accidental hypothermia. RESULTS: The literature reported many instances in which inhalation rewarming appeared to contribute to a successful outcome during hypothermic resuscitative efforts. The maximum contribution that inhalation rewarming provides to overall core rewarming does not appear to endorse it as a sole method of core rewarming. CONCLUSIONS: The safety and efficacy of inhalation rewarming suggest that it is a viable adjunct of treatment during hypothermic resuscitation. Its routine use may be more appropriate for a field rescue situation where more advanced rewarming modalities may not be available or practicable. Also, its primary value may be to minimize further core temperature loss during early management of accidental hypothermia.

Cardiopulmonary Resuscitation↗
PubMed2000

Acute exposure to the abused inhalant, isobutyl nitrite, reduced T cell responsiveness and spleen cellularity.

Isobutyl nitrite is an inhalant abused principally by male homosexuals. We have reported that subchronic inhalation exposure (45 min/day for 14 days) to 900 ppm isobutyl nitrite was immunosuppressive. In the present study, the effects of acute exposure to the inhalant were examined. Mice were exposed in an inhalation chamber to 900 ppm isobutyl nitrite for 45 min. One day later, spleen cellularity was reduced by 39% without selectively depleting CD4(+) or CD8(+) cells. The numbers of peripheral blood leukocytes and peritoneal cells were also reduced. Following acute inhalation exposure, T cell proliferative responses stimulated with allogeneic cells or anti-CD3 and anti-CD28 antibodies were inhibited, while mitogen-induced responses were not affected. Purified T cells exposed to the inhalant also had compromised responses, suggesting a direct effect on T cells. However, the cumulative effects of multiple exposures were necessary to inhibit T-dependent antibody responses or T cell or macrophage cytotoxicity.

Administration, Inhalation↗
PubMed2003

Overview of testing methods used in inhalation toxicity: from facts to artifacts.

For smaller rodent species, homogenous in size and growth, small head or nose-only chambers are commonly used up to subchronic exposure durations, whereas larger whole-body exposure chambers are used for long-term exposures or exposure paradigms exceeding the normal working day. The advantages and disadvantages of each different technique have already been identified and published in detail. It is often believed best that whole-body inhalation chambers simulate potential human exposure to environmental chemicals or pesticides and this serves as a justification for preferring this mode of exposure. However, real-life exposure conditions of humans cannot be readily duplicated. A comparable mode of exposure may be employed rather than duplicating both the exposure regimens and atmospheres similar to those present in real-world settings. Especially in inhalation studies with complex mixtures, in which atmosphere generation is difficult to control, non-homogenous exposure atmospheres and artifacts are more likely to occur in larger whole-body chambers than in the smaller nose-only inhalation chambers. Inhalation studies with complex mixtures not only face all the challenges of traditional inhalation toxicity testing, but also they are frequently subject to artifacts not readily detected. Thus, a disproportionation of volatile and particulate constituents might occur in inhalation chambers depend on selected technical features, i.e., whether a dynamic or (quasi)static mode of exposure is chosen. Inappropriate timing of the sampling of biological specimens may lead to the underestimation of effects, especially in whole-body exposed animals.

Administration, Inhalation↗
PubMed1999

Increased tumor growth in mice exposed to inhaled isobutyl nitrite.

Epidemiological studies have correlated the incidence of Kaposi's sarcoma (KS) in AIDS with a history of abuse of nitrite inhalants. To determine if exposure to nitrite inhalants could alter tumor growth, syngeneic PYB6 tumor cells were injected into groups of mice. Exposure of these mice to inhaled isobutyl nitrite increased both the tumor incidence and the tumor growth rate by almost 4-fold. Following only five daily exposures to the inhalant, the induction of specific T cell mediated cytotoxicity was inhibited by 36%. Similar inhalation exposures inhibited the tumoricidal activity of activated macrophages by 86%. The data suggest that exposure to abuser levels of a nitrite inhalant compromised tumor surveillance mechanisms.

Administration, Inhalation↗
PubMed2003

Air classifier technology (ACT) in dry powder inhalation. Part 1. Introduction of a novel force distribution concept (FDC) explaining the performance of a basic air classifier on adhesive mixtures.

Air classifier technology (ACT) is introduced as part of formulation integrated dry powder inhaler development (FIDPI) to optimise the de-agglomeration of inhalation powders. Carrier retention and de-agglomeration results obtained with a basic classifier concept are discussed. The theoretical cut-off diameter for lactose of the classifier used, is between 35 and 15 microm for flow rates ranging from 20 to 70 l/min. Carrier retention of narrow size fractions is higher than 80% for flow rates between 30 and 60 l/min, inhalation times up to 6s and classifier payloads between 0 and 30mg. The de-agglomeration efficiency for adhesive mixtures, derived from carrier residue (CR) measurement, increases both with increasing flow rate and inhalation time. At 30 l/min, 60% fine particle detachment can be obtained within 3s circulation time, whereas at 60 l/min only 0.5s is necessary to release more than 70%. More detailed information of the change of detachment rate within the first 0.5s of inhalation is obtained from laser diffraction analysis (LDA) of the aerosol cloud. The experimental results can be explained with a novel force distribution concept (FDC) which is introduced to better understand the complex effects of mixing and inhalation parameters on the size distributions of adhesion and removal forces and their relevance to the de-agglomeration in the classifier.

Adhesives↗
PubMed2000

Relationship of early inhalant use to substance use in college students.

This study examined the relationship between early inhalant use and later substance use in a sample of college students. Data were taken from four campus-wide surveys that assessed changes in rates of substance use over time at a large Southwestern university. Within these surveys, a group of students (n = 187) who reported early use of inhalants (i.e., before age 18) was identified and examined in terms of their substance use behavior while in college (i.e., during the year and month prior to the survey). These students were compared to two other groups of students: those who reported early use of marijuana but no early use of inhalants (n = 1271) and students who reported no early use of either inhalants or marijuana (n = 1479). Results show that early use of either inhalants or marijuana substantially increased risk of frequent drinking, binge drinking, smoking, illicit drug use, and substance-related consequences during the college years. However, the early use of inhalants conferred the greatest risk and was associated with twice the rate of binge and frequent drinking and significantly greater rates of tobacco and drug use than early marijuana use alone. Implications of these findings for intervention and prevention with college students are discussed.

Administration, Inhalation↗
PubMed1992

High dose inhaled steroid therapy and the cortisol stress response to acute severe asthma.

Systemic absorption of inhaled corticosteroids taken in high doses (> or = 1500 micrograms beclomethasone dipropionate or budesonide daily), may cause suppression of the hypothalamo-pituitary-adrenal axis. Patients taking long-term high dose inhaled steroid therapy might therefore be at risk of adrenal crisis at times of stress. Plasma cortisol levels were measured in 24 adults with severe acute asthma who had not received treatment with systemic corticosteroids prior to hospital attendance. Seven were not taking inhaled steroids, four were taking 600-1200 micrograms and 13 were taking 1500-2400 micrograms beclomethasone dipropionate or budesonide daily. Plasma cortisol levels in these 13 (median 594 nmol l-1, interquartile range 399-620 nmol l-1) were similar to levels in those taking lower dose/no inhaled steroids (median 512 nmol l-1, interquartile range 287-1050 nmol l-1): there was no relationship between inhaled steroid dose and cortisol level. Nine of the 24 patients failed to achieve plasma cortisol values > 500 nmol l-1 (the normal response to an insulin stress test). When compared with the remaining 15, they had less severe asthma as indicated by higher arterial oxygen tension (P < 0.01) and peak expiratory flow (P < 0.03). Patients taking long-term high dose inhaled corticosteroids appear to be able to mount an appropriate adrenocortical response to the stress of severe acute asthma.

Acute Disease↗
PubMed1996

Effect of inhaled beclomethasone on serum markers of collagen metabolism in postmenopausal asthmatic women.

The use of inhaled corticosteroids in bronchial asthma has widened, but there is a lack of data on their effect on bone collagen synthesis and degradation. This paper reports the effect of three dose levels (200, 1000 and 2000 micrograms day-1, 3 weeks each) of inhaled beclomethasone on specific characteristics of bone collagen metabolism in seven postmenopausal women with new asthma without any previous corticosteroid therapy. Serum aminoterminal (PINP) propeptide of human type I procollagen was seen, after an initial increase, to decrease significantly (from 42.2 to 35.5 micrograms l-1, P = 0.001) with the higher doses of inhaled beclomethasone, but no statistical change was found in the carboxyterminal propeptide (PICP) or type I collagen crosslinked telopeptide (ICTP). This data shows that type I collagen synthesis may be disturbed when using high-dose inhaled corticosteroids. However, further studies are needed to assess the effects of inhaled beclomethasone on the ability of the osteoblasts to form bone matrix, and on the density of bone during a longer treatment period with inhaled corticosteroids.

Administration, Inhalation↗
PubMed1996

Inhalers and nebulizers: which to choose and why.

It is obvious that many factors should be considered when an inhaler is prescribed. Based upon the information discussed above, a rational inhaler strategy could be as follows: (1) Children < or = 5 years and elderly patients are prescribed a spacer with a valve system (and a face mask for the children) for the delivery of all drugs. When they are severely obstructed, some may need a nebulizer. If the patient cannot be taught the correct use of a spacer, a nebulizer should be prescribed. (2) Children > or = 5 years and adults are prescribed a spacer or a Turbuhaler for the administration of inhaled corticosteroids and a dry powder inhaler (preferably multiple dose) or a breath-actuated MDI for other drugs. If these alternatives are not available or the patient prefers, a conventional MDI can be used (preferably not for other corticosteroids than fluticasone propionate) provided that careful tuition is given. Fluticasone dipropionate may be given by DPI, Spacer or MDI. (3) Nebulizers are mainly reserved for severe acute attacks of bronchoconstriction. With this approach, most patients can be taught effective inhaler use with a minimum of instructional time. Finally, it must always be remembered to consider the patient's wish, since prescription of an inhaler which the physician likes but the patient does not is likely to reduce compliance.

Administration, Inhalation↗
PubMed2000

Effects of inhaled nitric oxide on gas exchange and acute lung injury in premature lambs with moderate hyaline membrane disease.

OBJECTIVE: The purpose of this study was to examine whether inhaled nitric oxide (iNO) may change lung injury in moderate hyaline membrane disease (HMD). METHODS: Fifteen moderately premature lambs (128 days gestation, term=147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n=7) from the onset of ventilation or control (n=8). Except for inhaled NO, treatments were intentionally similar to those applied in clinical situations. After porcine surfactant administration (Curosurf, 100 mg/kg), mechanical ventilator settings were modified during the course of the study to maintain PaCO(2) between 40 and 50 mmHg and post-ductal SpO(2) between 90 and 95%. The main studied parameters were gas exchanges parameters, respiratory mechanics (static compliance and functional residual capacity) and pulmonary vascular permeability and/or filtration rate indices. RESULTS: We found that 20 ppm of inhaled NO for 5 h significantly reduce ventilatory and oxygen requirements, but only during the first hour of mechanical ventilation. No increase in extravascular lung water content (5.41+/-0.96 vs. 5.46+/-1.09 ml/g bloodless dry lung in the control group and in the NO group, respectively) and no impairment of the respiratory mechanics could be found in the NO-treated group. However, inhaled NO increased the albumin lung leak index in this model (6.09+/-1.51 in the NO-treated group vs. 4.08+/-1.93 in the control group; P<0.05). CONCLUSIONS: Our results do not therefore support a detrimental effect of short-term exposure to low doses of NO inhalation in moderate HMD. However, it may induce an increase in lung vascular protein leakage. The pathophysiological consequences of this finding remain to be elucidated.

Administration, Inhalation↗
PubMed1997

Inhaled nitric oxide after lung ischemia reperfusion; effect on hemodynamics and oxygen free radical scavenger system.

OBJECTIVE: Pulmonary hypertension and transient graft dysfunction may complicate the postoperative course of patients undergoing lung transplantation. Recent studies have suggested that ischemia followed by reperfusion impairs release of endothelium-derived nitric oxide (NO). We investigated the acute effect of inhaled NO on hemodynamics and the oxygen free radical scavenger system after reperfusion following lung ischemia. METHODS: Fourteen anesthetized mongrel dogs were ventilated mechanically. After median sternotomy the left lung was rendered ischemic by totally clamping the left pulmonary hilum. After 90 min, the left lung was reperfused for 150 min by unclamping of the left hilum and clamping the right pulmonary hilum so that all pulmonary blood flow was directed to the left lung. Seven dogs inhaled 30 parts per million (ppm) NO during reperfusion (NO group); the other seven dogs were ventilated without NO inhalation (control group). Hemodynamics, gas exchange, superoxide dismutase activity and lipid peroxide of pulmonary venous blood, and wet/dry ratio of reperfused lung were measured. RESULTS: Neither of the two groups showed any change in systemic blood pressure prior to or following reperfusion. Immediately after reperfusion, mean pulmonary arterial pressure was significantly less (23.2 +/- 4.2 mmHg) in the NO group than in the control group (32.7 +/- 5.8 mmHg), as had been throughout reperfusion. Pulmonary vascular resistance and right ventricular end diastolic pressure were lower after reperfusion in the NO group. Superoxide dismutase activity after reperfusion in the control group significantly decreased to 41% of preischemic value. In the NO group, however, no decrease was seen and a significantly higher value was observed. The wet/dry ratio of reperfused lung was 5.47 +/- 0.52 in the control group and 4.72 +/- 0.36 in the NO group, with decreased pulmonary moisture noted in the NO group. There was no difference in lipid peroxide between the two groups. CONCLUSION: NO inhalation suppressed pulmonary hypertension after reperfusion following lung ischemia without affecting systemic arterial pressure. As superoxide dismutase activity was not depressed in the NO group, NO inhalation might enhance suppression of oxygen free radicals. These findings suggest that NO inhalation may be therapeutically useful after lung transplantation.

Administration, Inhalation↗