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PubMed1999

Do subjects with asthma have greater perception of acute bronchoconstriction than smokers with airflow limitation?

OBJECTIVE: Smokers who develop chronic airflow limitation (CAL) do not usually present for medical attention until their lung disease is well advanced. In contrast, asthmatic subjects experience acute symptoms and present for care early in the course of their disease. The aim of this study was to determine whether subjects with asthma differ from smokers with CAL in their ability to perceive acute methacholine-induced bronchoconstriction. METHODOLOGY: Thirteen subjects with diagnosed asthma and 10 current smokers with CAL, defined as forced expiratory volume in 1 s (FEV1) < 75% predicted and FEV1/forced vital capacity < 80%, with no previous diagnosis of asthma, were challenged with methacholine. Symptom severity was recorded on a Borg scale. Lung volumes were measured before challenge and after the FEV1 had fallen by 20%. RESULTS: After methacholine falls in FEV1 were similar in the asthmatic subjects and smokers. The regression lines relating change in FEV1 to symptom score were significantly steeper in asthmatic subjects than smokers (0.13 +/- 0.04, 0.03 +/- 0.04, respectively, P < 0.01). At 20% fall in FEV1 there were no significant differences between asthmatic subjects and smokers in the magnitude of change of lung volumes. CONCLUSIONS: In asthmatic subjects, symptoms are closely related to change in FEV1. In smokers with CAL, symptoms change little during bronchial challenge despite large changes in FEV1. The differences in perception between the two subject groups are not due to differences in acute hyperinflation during challenge. We propose that heavy smokers may adapt to poor lung function, or may have damaged sensory nerves as a result of prolonged cigarette smoking.

Aged↗
PubMed2000

Post-inhalation bronchoconstriction by beclomethasone dipropionate: a comparison of two different CFC propellant formulations in asthmatics.

OBJECTIVE: To assess the change in bronchial response to cumulative doses from two beclomethasone dipropionate metered-dose inhalers (MDI), each using chlorofluorocarbon (CFC) propellants, in asthma patients previously showing falls in forced expiratory volume in 1 s (FEV1) shortly after exposure to beclomethasone MDI. METHODOLOGY: A total of 18 patients were randomized to a single-blind, three-period cross-over treatment regimen, whereby each was administered increasing doses of control mixture (containing surfactant and CFC propellants) or beclomethasone, formulated as either Becloforte or Respocort (250-1000 microg per dose; cumulative dose 2000 microg). Bronchial response was measured by comparison of FEV1 values pre- and post-inhalation. RESULTS: Respocort formulation produced the least post-dose mean maximum reduction in FEV1 (0.36 +/- 0.17 L; 14.3 +/- 7.2% of baseline FEV1), while the reduction caused by the control was similar (0.40 +/- 0.18 L; 16.2 +/- 9.9% of baseline FEV1). Becloforte produced a significantly greater maximum reduction in FEV1 than Respocort (0.55 +/- 0.32 L, P = 0.003; 22.0 +/- 15.3% of baseline FEV1, P = 0.005). No serious adverse events were reported, but four patients experienced falls in FEV1 of greater than 15% (three on Becloforte, one using the control). CONCLUSION: The incidence of falls in FEV1 following use of beclomethasone MDI was low and generally not serious even in a selected population. The Becloforte preparation produced significantly more post-dose bronchoconstriction than the Respocort formulation, perhaps because of differences in the composition of the surfactant and/or CFC propellant mixtures used to formulate each of the aerosols.

Administration, Inhalation↗
PubMedDate not supplied

Bronchoconstrictive properties of inhaled 8-epi-PGF2alpha in healthy and heaves-susceptible horses.

The 8-epi-PGF2alpha is a marker of oxidative stress which is increased in lungs of asthmatic humans and heaves-susceptible horses. 8-Epi-PGF2alpha has also been demonstrated to be an in vitro and in vivo bronchoconstrictor in humans and rodents. We hypothesised that inhaled 8-epi-PGF2alpha was a bronchoconstrictor in healthy and heaves-susceptible horses in clinical remission. The effect on ventilatory mechanics of nebulised 8-epi-PGF2alpha was compared to that of PGF2alpha and U46619, a thromboxane A2 agonist. Pulmonary resistance (R(L)) and dynamic compliance (Cdyn) were assessed in six healthy horses and in six heaves-susceptible horses in clinical remission before (baseline) and immediately after a single inhalation challenge of 1 mg 8-epi-PGF2alpha PGF2alpha, or U46619 and placebo. R(L) and Cdyn were unchanged after inhalation of 8-epi-PGF2alpha in healthy horses. In heaves-susceptible horses, 8-epi-PGF2alpha induced a significant increase of R(L) and a significant decrease of Cdyn when compared to baseline values. Differences between R(L) and Cdyn values after 8-epi-PGF2alpha inhalation and those of placebo inhalation were not significant. Differences with healthy horses were not significant. PGF2alpha and U46619 induced a significant bronchoconstriction in healthy (R(L) and Cdyn versus baseline) and heaves-susceptible horses (R(L) and Cdyn, versus baseline and placebo), the R(L) increase in heaves-susceptible horses after PGF2alpha inhalation was significantly higher than that in healthy horses. Our results suggest that 8-epi-PGF2alpha is not a bronchoconstrictor in healthy horses, and a bronchoconstrictor far less efficient than PGF2alpha and U46619 at the same dose in heaves-susceptible horses.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Exercise-induced bronchoconstriction depends on exercise load.

UNLABELLED: Exercise-induced bronchoconstriction (EIB) is often used as a measure of bronchial hyperresponsiveness and employed in epidemiological studies. Different tests are used, including free running tests with poor standardization of exercise load. The present study aimed to assess the role of exercise load in relationship to level of EIB. METHODS: 20 asthmatic children, 9-17 years old with a history of EIB, underwent two treadmill test with 85% and 95% exercise load. The children ran with increasing speed for the first 2 min until reaching a heart rate of 85% or 95% of calculated maximum (220-age) and maintained this speed for the last 4 min. Lung function was measured before running, and 0, 3, 6, 10 and 15 min after the run. Borg scale for perceived exertion was employed for children's self-evaluation of exercise load. RESULTS: Peak heart rate, mean Borg score during 85% exercise load was 178.7/13.6 and during 95% was 194.3/18.2 (P<0.001). Maximum fall in FEV1 after 85% exercise load was 8.84% vs. 25.11% after 95% (P<0.001). Nine subjects (40%) fell > or = 10% in FEV1 after 85% exercise load vs. 20 subjects (100%) after 95% exercise load. EIB from the 95% exercise load test had markedly higher correlation with serum ECP (r=0.77, P<0.001). CONCLUSION: Exercise load is essential for the interpretation of EIB, and strict standardization of exercise tests should be undertaken. The EIB from the high exercise load tests seemed better correlated to inflammatory activity than the low exercise load test.

Adolescent↗
PubMed2001

Protection against cold air and exercise-induced bronchoconstriction while on regular treatment with Oxis.

This study aimed to compare the duration of protection against exercise-induced bronchoconstriction (EIB) after inhalation of formoterol (Oxis) Turbuhaler with that of terbutaline Turbuhaler and placebo Turbuhaler in asthmatic patients treated regularly with formoterol Turbuhaler 9 microg b.i.d. and inhaled steroids. The study. performed at three centres (Göteborg and Lund, Sweden, and Trondheim, Norway), consisted of an open-label part with formoterol Turbuhaler 9 microg b.i.d. and a randomized, double-blind, cross-over part with a single dose (on top of the regular treatment) of either formoterol Turbuhaler 9 microg, terbutaline Turbuhaler 0.5 mg or placebo Turbuhaler. The patients attended the clinic six times: twice for screening visits, three times for randomized treatment and once for a follow-up visit. Patients received regular b.i.d. treatment with formoterol 9 microg for a mean period of 16 days. Formoterol gave a post-exercise fall of 12, 10, 15 and 17% in forced expiratory volume in 1 sec (FEV1) 15 min, 4, 8 and 12 h after inhalation. The differences compared with placebo (falls of 26, 22, 23 and 22%) and terbutaline (falls of 17, 18, 22 and 22%) were all statistically significant (P<0.05 for all comparisons). Patients on regular treatment with formoterol Turbuhaler 9 microg b.i.d. have a significant protection against EIB up to 12 h after inhalation of formoterol 9 microg. The protection was also significantly better than that of terbutaline Turbuhaler 0.5 mg.

Adult↗
PubMed2000

The bronchoconstrictive action of evodiamine, an indoloquinazoline alkaloid isolated from the fruits of Evodia rutaecarpa, on guinea-pig isolated bronchus: possible involvement on vanilloid receptors.

Evodiamine, a constituent of Evodiae Fructus (Evodia rutaecarpa Benth., Rutaceae), produced a bronchial contraction that is resistant to atropine and abolished by pretreatment with a mixture of the NK1 and NK2 receptor antagonists. Contractile responses to evodiamine were examined in guinea-pig isolated bronchus and compared with those to capsaicin. Both compounds evoked bronchial contraction in a concentration-dependent manner. Maximal contractions for evodiamine and capsaicin were observed at concentrations of 3 microM and 1 microM, respectively. Capsazepine (10 microM), an established antagonist of vanilloid receptor (capsaicin receptor), competitively inhibited the bronchial contraction evoked by evodiamine, suggesting that evodiamine activated vanilloid receptors. Evodiamine (3 microM) and capsaicin (1 microM) produced complete crossed tachyphylaxis. Both compounds desensitized tissues to subsequent additions of either evodiamine or capsaicin. These results suggest that the evodiamine-induced contractile response of the bronchus could be attributed to the resultant tachykinin release from sensory neurons by binding of evodiamine to vanilloid receptors. Rutaecarpine, which belongs to the same indoloquinazoline-type alkaloid as evodiamine, showed neither bronchoconstrictive, desensitizing effects nor vanilloid antagonistic effects at all the concentrations examined (up to 200 microM).

Animals↗
PubMed2005

Undiagnosed exercise-induced bronchoconstriction in ski-mountaineers.

Because the practise conditions put the ski-mountaineering athletes potentially at risk for exercise-induced bronchoconstriction (EIB), this study was conducted to estimate the prevalence of EIB in this population. Thirty-one highly-trained ski-mountaineers with racing experience participating in the race were evaluated. EIB was determined after a European race at high altitude and frigid conditions. Pre-race investigations included pulmonary function measurements and a questionnaire enquiring about i) training habits, ii) respiratory history during training and/or competition. Pulmonary function was also tested after the race. None of the athletes reported a basal airway obstruction. Two groups were determined after post-race airway response: i) EIB (+) group exhibiting a fall in FEV (1) > or = 10 % (n = 15) and ii) EIB (-) without fall in FEV (1) or fall < 10 % (n = 16). Neither training habits nor baseline lung function were associated with the post-race airway response. Six of the 31 ski-mountaineers had a previous physician-made diagnosis of asthma and/or EIB, nevertheless 23 of our athletes complained about at least one characteristic symptom of asthma during practise. Four of our 15 EIB (+) had a previous physician-made diagnosis of asthma/EIB indicating that 73 % of EIB (+) athletes were undiagnosed for EIB. The proportion of allergic athletes was not significantly different between EIB (+) and EIB (-). This study showed that approximatively half of highly-trained ski-mountaineers with racing experience can develop EIB after a race and that 73 % of them are unaware of the problem.

Adult↗
PubMed2000

Mometasone furoate antagonizes AMP-induced bronchoconstriction in patients with mild asthma.

BACKGROUND: Mometasone furoate (MF) is a new potent corticosteroid for use in treating asthma. OBJECTIVE: To test the lower range of the dose-response curve, effects of MF delivered by dry powder inhaler (DPI) on AMP-induced bronchoconstriction were compared with those of placebo. METHODS: In a placebo-controlled, 3-phase cross-over, single-center, double-blind study, 15 patients with mild asthma were randomized to three 2-week treatment phases (separated by 4-week washout phases) with MF DPI 50 microg twice daily, MF DPI 100 microg twice daily, or placebo. AMP challenge was performed before and at the end of each treatment phase. RESULTS: Thirteen patients completed all 3 phases and were included in the primary efficacy analysis. Treatment with MF DPI 50 microg twice daily or with MF DPI 100 microg twice daily significantly reduced the bronchoconstrictor response to AMP, displacing the dose-response curve to the right by 2.81 and 3.11 doubling dilutions, respectively, compared with placebo (P <.001). The improvement in FEV(1) over the 2-week treatment phase was significantly (P < or =.033) greater during treatment with MF DPI 50 microg or 100 microg twice daily than with placebo. Peak expiratory flow rate, wheezing scores, difficulty breathing scores, nocturnal awakenings requiring salbutamol, and puffs of salbutamol per day also indicated a greater improvement in respiratory function and symptoms of asthma with MF DPI 50 or 100 microg twice daily than with placebo. Both doses of MF DPI were well tolerated. CONCLUSIONS: Treatment with low doses of MF DPI decreased airway responsiveness to AMP challenge and improved secondary measures of pulmonary function and asthma symptoms.

Adenosine Monophosphate↗
PubMed2000

Perception of induced bronchoconstriction in a community sample of adolescents.

BACKGROUND: Poor perception of asthma symptoms has been cited as a risk factor for asthma death, yet there is no consensus as to the best way to characterize perception, and little is known about perception in normative samples. Hypoperceivers are of clinical interest because of risks of undertreatment; hyperperceivers are at risk for adverse iatrogenic effects caused by overtreatment. OBJECTIVE: This study investigates perception of methacholine-induced bronchoconstriction in 175 adolescents. METHODS: Breathlessness was rated after each inhalation by using the Borg scale. Perception groups were calculated on the basis of change from placebo Borg to high Borg scores (perception score at the highest methacholine dose). Subjects were called hypoperceivers if their Borg change score was greater than 1 SD below the mean for their FEV(1) group, hyperperceivers if their Borg change score was greater than 1 SD above the mean for their FEV(1) group, and accurate perceivers otherwise. RESULTS: For subjects with an FEV(1) drop of less than 10%, accurate perceivers had a change in Borg score of 1.4 or less, and hyperperceivers had a change of greater than 1.4. For a drop in FEV(1) between 10% and 19%, hypoperceivers had a change in Borg score of less than 0.2, accurate perceivers had a change between 0.2 and 2.1, and hyperperceivers had a change of greater than 2.1. For those with an FEV(1) drop of 20% or greater, hypoperceivers had a Borg change of less than 0.2, accurate perceivers had a change between 0.2 and 2.6, and hyperperceivers had a change of greater than 2.6. No differences in age, sex, placebo Borg ratings, baseline pulmonary functions, PC(20) values, or psychologic variables were found among perception groups. CONCLUSION: This study provides reference Borg values during methacholine challenge for 175 community adolescents.

Adolescent↗
PubMedDate not supplied

Impulse oscillometry is sensitive to bronchoconstriction after eucapnic voluntary hyperventilation or exercise.

Airway responses were compared following 6-minute eucapnic voluntary hyperventilation and 6-minute exercise challenges by examining resting and post-challenge impulse oscillometry and spirometry variables. Twenty-two physically active individuals with probable exercise-induced bronchoconstriction took part in this study. Impulse oscillometry and spirometry were performed at baseline and for 20 minutes post-challenge at 5-minute intervals. High correlation was found between the two measures of change in airway function for both methods of challenge. Impulse oscillometry detected a difference in degree of response to the challenges, whereas spirometry indicated no difference, suggesting that impulse oscillometry is a more sensitive measure of change in airway function.

Adolescent↗
PubMed2004

Loss of vagally mediated bradycardia and bronchoconstriction in mice lacking M2 or M3 muscarinic acetylcholine receptors.

The presence of multiple muscarinic acetylcholine receptor (mAChR) subtypes in the heart and lung, combined with the lack of mAChR subtype-selective ligands, have complicated the task of identifying the mAChR subtypes mediating cardiac slowing (bradycardia) and airway narrowing (bronchoconstriction) due to vagal innervation. To determine which of the five mAChRs are responsible for the cholinergic control of heart rate and airway caliber in vivo, we performed experiments on mutant mice lacking the two prime candidates for such control, the M2 or M3 mAChR. Here, we report that in vivo, bradycardia caused by vagal stimulation or administration of the muscarinic agonist methacholine (MCh) was abolished in mice lacking functional M2 mAChRs (M2-/- mice). In contrast, heart rate responses remained unchanged in M3 receptor-deficient mice (M3-/- mice). The reduced hypotensive response of M3-/- mice to MCh suggests M3 mAChRs contribute to peripheral vasodilation. The M2-/- mice showed significantly enhanced in vivo bronchoconstrictor responses to vagal stimulation or MCh administration. In contrast, bronchoconstrictor responses were totally abolished in M3-/- mice. Because altered cardiac or pulmonary vagal tone is involved in a number of pathophysiological conditions, including cardiac arrhythmias, chronic obstructive pulmonary disease and asthma, these results should be of considerable therapeutic relevance.

Animals↗
PubMed2001

Propofol-induced bronchoconstriction: two case reports.

IMPLICATIONS: Bronchoconstriction was induced by anesthetic induction with propofol in two patients with allergic diseases. One had severe bronchospasm improved by epinephrine. Propofol should be used with caution in patients with allergic disease.

Adult↗
PubMed2002

Both local anesthetics and salbutamol pretreatment affect reflex bronchoconstriction in volunteers with asthma undergoing awake fiberoptic intubation.

BACKGROUND: Awake tracheal intubation may evoke reflex bronchoconstriction in asthmatics. Whether this effect is altered by the choice of the local anesthetic used or by pretreatment with a beta2-adrenoceptor agonist is unknown. Therefore, we assessed the effect of awake fiberoptic intubation after lidocaine or dyclonine inhalation with or without pretreatment with salbutamol on lung function in asthmatic volunteers. METHODS: Bronchial hyperreactivity was verified by an inhalational histamine challenge. On four different days in a randomized, double blind fashion the volunteers (n = 10) inhaled either dyclonine or lidocaine with or without salbutamol pretreatment. FEV1 was measured at baseline, following salbutamol or saline inhalation, after lidocaine or dyclonine inhalation, while intubated, and after extubation. Lidocaine and dyclonine plasma concentrations were also measured. STATISTICS: Two-way ANOVA, post hoc tests with Bonferroni correction, results are presented as mean +/- SD. RESULTS: Neither lidocaine nor dyclonine inhalation changed FEV1 significantly from baseline compared with placebo inhalation (4.43 +/- 0.67 l vs. 4.29 +/- 0.72 l, and 4.53 +/- 0.63 l vs. 4.24 +/- 0.80 l, respectively). Salbutamol slightly but significantly increased FEV1 (4.45 +/- 0.76 l vs. 4.71 +/- 0.61 l, P = 0.0034, and 4.48 +/- 0.62 l vs. 4.71 +/- 0.61 l, P = 0.0121, respectively). Following awake intubation FEV1 significantly decreased under lidocaine topical anesthesia (4.29 +/- 0.72 l to 2.86 +/- 0.87 l) but decreased even more under dyclonine anesthesia (4.24 +/- 0.80 l to 2.20 +/- 0.67 l; P < 0.0001). While salbutamol pretreatment significantly attenuated the response to intubation, it did not eliminate the difference between the effects of lidocaine and dyclonine. Only minutes after extubation FEV1 was similar compared with baseline. CONCLUSION: In asthmatics, awake fiberoptic intubation evokes a more than 50% decrease in FEV1 following dyclonine inhalation. Using lidocaine for topical anesthesia the decrease in FEV1 is significantly mitigated (35%) and can be even further attenuated by salbutamol pretreatment. Therefore, combined treatment with lidocaine and salbutamol can be recommended for awake intubation while the use of dyclonine, despite its excellent and longer lasting topical anesthesia, may be contraindicated in patients with bronchial hyperreactivity.

Adult↗
PubMed2002

Intravenous colforsin daropate, a water-soluble forskolin derivative, prevents thiamylal-fentanyl-induced bronchoconstriction in humans.

OBJECTIVE: Forskolin, a direct activator of adenylate cyclase, can relax airway smooth muscle, similar to other agents that increase intracellular cyclic adenine monophosphate. However, the potential usefulness of forskolin in treating bronchospasm is limited by its poor water solubility. Colforsin daropate is a novel and potent water-soluble forskolin derivative. No clinical data have been published on the bronchorelaxant effects of this drug. The aim of this study was to investigate whether intravenous colforsin daropate prevents thiamylal-fentanyl-induced bronchoconstriction. DESIGN: Double-blind, prospective, placebo-controlled randomized study. SETTING: University teaching hospital. PATIENTS: Thirty-six patients were allocated randomly to two groups: the control group (n = 18) and colforsin daropate group (n = 18). INTERVENTIONS: Intravenous administration of colforsin daropate or placebo (normal saline). MEASUREMENTS AND MAIN RESULTS: Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.3 mg/kg. A 15 mg x kg(-1) x hr(-1) continuous infusion of thiamylal followed anesthetic induction. Controlled ventilation was maintained, delivering 50% nitrous oxide in oxygen. Twenty minutes after the induction of anesthesia, the control group patients started to receive 7.5 mL/hr continuous infusion of normal saline, and the colforsin daropate group patients started to receive 0.75 microg x kg(-1) x min(-1) (7.5 mL/hr) continuous infusion of colforsin daropate for 60 min. After that, both groups received fentanyl 5 microg/kg. Systolic and diastolic arterial pressure, heart rate, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured at the baseline, just before the administration of fentanyl (T30), at three consecutive 6-min intervals after fentanyl injection (T36, T42, and T48) and 30 min after fentanyl injection (T60). At baseline, both groups had comparable Rawm, Rawe, and Cdyn values. In the control group, Rawm increased significantly at T36-60 compared with the baseline, Rawe increased significantly at T36-48 compared with the baseline, and Cdyn decreased significantly at T36-60 compared with the baseline. In the colforsin daropate group, there were no changes in Rawm, Rawe or Cdyn at T36-60. CONCLUSIONS: These observations suggest that intravenous colforsin daropate has a bronchodilator effect in humans.

Adult↗
PubMed1991

Multiple mechanisms of bronchoconstrictive responses to endothelin-1.

We investigated the mechanism of the endothelin-1 (ET-1)-induced bronchoconstriction of guinea pig tracheal smooth muscles. ET-1 contracted the tracheas in a dose-dependent manner. A combination of FPL55712 (leukotriene antagonist), diphenhydramine (histamine antagonist), and indomethacin (cyclooxygenase inhibitor) shifted the dose-response curve of ET-1 to the right and suppressed the maximal constriction. Azelastine, an antiallergic agent, exerted essentially similar results. The present data suggest that ET-1 constricts the airway smooth muscles not only by direct action on the tracheal smooth muscles but also by indirect action mediated through production of various chemical mediators in cells other than muscles.

Animals↗
PubMed2004

Screening of athletes for exercise-induced bronchoconstriction.

Exercise-induced bronchoconstriction (EIB) has a high prevalence in elite athletes, particularly endurance athletes, winter athletes and swimmers. Recent studies have shown that a clinical diagnosis of EIB has only a moderate sensitivity and specificity for EIB. This finding in conjunction with a recent ruling by the IOC-medical commission that all athletes competing in initially the 2003 Winter Olympic Games in Salt Lake City, and now the 2004 Summer Olympic Games in Athens require objective evidence of EIB, support the need for bronchial provocation challenge tests in the diagnosis of EIB. The recommended bronchial provocation challenge test is the eucapnic voluntary hyperpnea (EVH) challenge; this challenge test has been shown to have both a high sensitivity and specificity for EIB. Pharmacological challenge tests, such as the methacholine challenge test, have been shown to have only a low sensitivity but high specificity for EIB in elite athletes, and are thus not recommended in the athlete with pure EIB. Exercise challenge tests performed both in the laboratory and field have a high specificity for EIB; however those in the laboratory have only a moderate sensitivity for EIB in elite athletes, whilst those in the field are limited by problems with standardization. The osmotic challenge tests, such as the hypertonic saline and newer inhaled dry powder mannitol challenge have both a high sensitivity and specificity for EIB, and may be used as an alternative to the EVH challenge.

Asthma, Exercise-Induced↗
PubMed2003

Intravenous nicorandil prevents thiamylal-fentanyl-induced bronchoconstriction in humans.

OBJECTIVE: Nicorandil has a hybrid property between nitrates and potassium channel openers and has been reported to cause a concentration-dependent relaxation of isolated guinea pig trachealis. Experimental asthma in a guinea pig model was also inhibited by nicorandil. However, no clinical data on the bronchorelaxant effects of this drug have been published. The aim of this study was to investigate whether intravenous nicorandil prevents thiamylal-fentanyl-induced bronchoconstriction. DESIGN: Double-blind, prospective, placebo-controlled, randomized study. PATIENTS: A total of 36 patients were randomly allocated to two groups: a control group (n = 18) and a nicorandil group (n = 18). INTERVENTIONS: Intravenous administration of nicorandil or a placebo (normal saline). MEASUREMENTS AND MAIN RESULTS: Anesthesia was induced with 5 mg/kg thiamylal and 0.3 mg/kg vecuronium. A continuous infusion of 15 mg x kg(-1) x hr(-1) thiamylal was then used to maintain the anesthesia. Controlled ventilation was maintained, delivering 50% nitrous oxide in oxygen. At 20 mins after the induction of anesthesia, the control group patients were given a 6 mL/hr continuous infusion of normal saline and the nicorandil group patients were given a 6 mg x hr(-1) (6 mL/hr) continuous infusion of nicorandil for 60 mins. At 30 mins after the start of the study, both groups received a 5-microg/kg dose of fentanyl. Systolic and diastolic arterial pressure, heart rate, mean airway resistance, expiratory airway resistance, and dynamic lung compliance were measured for the baseline condition, just before the administration of fentanyl (T30), at three consecutive 6-min intervals after the fentanyl injection (T36, T42, and T48) and 30 mins after the fentanyl injection (T60). Both groups had comparable baseline values for mean airway resistance, expiratory airway resistance, and dynamic lung compliance. In the control group, both mean airway resistance and expiratory airway resistance increased significantly at T36-60, compared with the baseline values, and dynamic lung compliance decreased significantly at T36-60, compared with the baseline value. In the nicorandil group, no changes in mean airway resistance, expiratory airway resistance, or dynamic lung compliance occurred at T36-60. CONCLUSIONS: Our observations suggest that the intravenous administration of nicorandil has a bronchodilator effect in humans.

Adult↗
PubMed1991

Salbutamol inhibits metabisulphite-induced bronchoconstriction.

The effect of salbutamol on bronchoconstriction induced by inhaled sodium metabisulphite has been studied in 12 atopic subjects. Salbutamol (200 micrograms, 3.5 x 10(-7) M) and matched placebo were administered by identical metered dose inhaler 15 min before a dose-response to sodium metabisulphite (1.25-100 mg ml-1) was performed. Geometric mean provocative dose of metabisulphite causing a 35% fall in sGaw after placebo pretreatment was 12.8 [5.75-28.1, 95% Cl] mumol, and after salbutamol was 75.9 [46.5-126] mumol. Mean maximum fall in sGaw after placebo pre-treatment was 47.4 [41-53.9]%. At the same metabisulphite concentration mean maximum fall in sGaw after salbutamol was 2.9 [-8.2-14.1]%.

Albuterol↗