Michiko Okayama

Treatment of status asthmaticus with intravenous magnesium sulfate

The bronchodilating effect of magnesium sulfate (MgSO4) was studied in two patients with status asthmaticus, who were intubated and mechanically ventilated by a respirator. Airway resistance was continuously monitored by the respiration-controlled interruption technique. After administration of 0.5 mmol/min MgSO4 intravenously, airway resistance decreased from 17 to 9, and from 13 to 8 mmHg/L/s in the two patients, respectively, and piping rales diminished or disappeared. We conclude that while corticosteroid therapy requires several hours to demonstrate significant effects in status asthmaticus, MgSO4 is of great benefit in the rapid improvement of airflow obstruction.

A new method of inhalation challenge with propranolol: comparison with methacholine-induced bronchoconstriction and role of vagal nerve activity.

To establish a safe procedure for examining propranolol-induced bronchoconstriction, we have developed a new method for performing inhalation challenge with propranolol. Monitoring respiratory resistance during tidal breathing with continuous inhalation of propranolol in 1.5-fold increasing concentrations from 0.78 to 30 mg/ml for 1 minute at each concentration, we tested 43 subjects with stable asthma and 10 normal subjects. We also compared bronchial responsiveness with responsiveness to inhaled methacholine on separate days. In addition, to determine the role of vagal nerve activity in propranolol-induced bronchoconstriction, we studied the effect of atropine. Inhaled propranolol caused dose-related bronchoconstriction in all subjects with asthma but not in normal subjects. None of the subjects suffered severe asthmatic attack during the test, which was performed in 15 minutes or less. The minimum cumulative dose of methacholine and of propranolol, at the point where respiratory conductance began to decrease, was not significantly correlated. Increased respiratory resistance was reversed by atropine in 70% of the subjects with asthma with marked individual differences. These data suggest that, although in most subjects with asthma, vagal nerve activity contributes in varying degree to bronchoconstriction, other constricting factors may contribute in the remaining subjects. It is also suggested that the mechanism of bronchial response to propranolol differs from that of the nonspecific airway reactivity estimated by methacholine challenge.

Characterization and Autoradiographic Localization of Histamine H1 Receptors in Human Nasal Turbinates

To examine the localization of histamine H1 receptors (H1R) in human nasal mucosa, the autoradiographic distribution of H1R was studied in human nasal inferior turbinates. Cryostat sections were incubated with various concentration of [3H]pyrilamine in saturation-binding studies and with 1 nmol/L of [3H]pyrilamine for autoradiography. Nonspecific binding was determined by adding 2 mumol/L of pyrilamine. Scatchard analysis demonstrated high-affinity binding sites with a maximum binding capacity of H1R of 193 +/- 46 fmol/mg of protein, and dissociation constant was 0.6 +/- 0.1 nmol/L. Autoradiograms indicated H1R exist exclusively on the endothelium of vessels. No specific labeling could be observed in the submucosal glands or epithelium. These results extend and support our previous finding that histamine directly causes vascular permeability through H1R and stimulates nasal glandular secretion indirectly through reflexes.

Bronchodilator effect of sublingual isosorbide dinitrate in asthma

SummaryThe bronchodilating effect of 5 mg sublingual isosorbide dinitrate (ISDN) was studied in 10 patients with bronchial asthma, using the doubleblind randomised cross-over method with matched placebo. In a further 20 asthmatics the effect of sublingual ISDN was compared with that of metaproterenol given by a metered dose inhaler to a total dose of 2.25 mg, again using the cross-over method. The forced oscillation method was used to measure respiratory resistance (Rrs) and spirometry was used to measure vital capacity (VC) and forced expiratory volume in one second (FEV1). 5 minutes after administration of ISDN Rrs had decreased (p<0.05) and VC (p<0.01) and FEV1 (p<0.01) were significantly increased. The changes were still present after 15, 30 and 60 min. The placebo had no significant effect. ISDN increased FEV1 less than metaproterenol, and the difference between them was statistically significant (p<0.05). However, there was no significant difference between ISDN and metaproterenol in the improvement in Rrs and VC. Of the total of 30 patients, 11 experienced headache and 4 had transient hypotension after ISDN administration. These side effects subsided spontaneously. It was concluded that sublingual ISDN had a bronchodilating effect in stable asthmatics.

Methacholine Bronchial Hyperresponsiveness inChronic Sinusitis

The coexistence of chronic sinusitis (CS) may deteriorate the clinical condition of lower airway diseases such as bronchial asthma (BA) or chronic bronchitis (CB). However, the bronchial hyperresponsiveness (BH) in CS without any apparent lower airway disease is not fully understood nor are the effects of treatment. We examined lower airway hyperresponsiveness to methacholine (MCh) in 42 subjects with CS but without allergic rhinitis (AR) who had normal lung functions without any pulmonary symptoms, comparing it with that of 50 subjects with stable BA, 50 subjects with simple CB and 40 subjects with AR, and further examined the effect of endoscopic sinus surgery in 7 CS subjects with BH. The BH to MCh was measured in terms of the minimum dose (Dmin), defined as the cumulative dose at the point where respiratory conductance began to decrease. A Dmin <50 units was defined as BH. Seventy-one percent of CS subjects showed BH without relation to the severity or duration of CS, or atopic status. BH in CS subjects, which was less than that in BA subjects, was similar to that in simple CB or AR in both its prevalence and degree. After the surgical treatment of CS, BH significantly decreased (p < 0.01) with improvements in both nasal symptoms and sinus lesions. These findings suggest that CS itself induces BH to a degree similar to simple CB and AR without any relationship to the clinical background, and that adequate treatment of CS reduces BH.

Localization of histamine N-methyltransferase messenger RNA in human nasal mucosa

BACKGROUND Histamine is metabolized mainly by histamine N-methyltransferase (HMT) to N tau-methylhistamine in human nasal mucosa. Human HMT cDNA has been cloned and expressed in COS cells. The purpose of this study was to determine the localization of HMT METHODS: The fragment (nucleotide residues 430-1055) of human HMT cDNA was subcloned in a Bluescript vector (Stratagene, La Jolla, Calif.), and HMT sense anti-sense RNA probes were made with T7 and T3 RNA polymerases. In situ hybridization with digoxigenin-labeled RNA probes was performed on surgical specimens of human nasal turbinates. RESULTS HMT mRNA was localized in cells in the epithelium and submucosa, and densely in endothelial cells of vessels. No HMT mRNA was identified in the submucosal glands. The presence of HMT mRNA was confirmed by Northern blot analysis, and HMT activities were also detected in nasal mucosa. CONCLUSION Our study indicates that endothelium expresses HMT mRNA, whereas cells in the epithelium and submucosa, which remain unidentified, are an additional source of HMT mRNA.

Isobaric force-velocity relationship of in situ canine trachealis muscle.

We measured the force-velocity relationship of the in situ trachealis muscle during vagal stimulation in six anesthetized dogs. The trachea, about 10 cm in length, was transected above the carina and left in situ with its blood supply intact, and its cut ends artificially closed. The lung was ventilated by a respiratory. First the vagal nerves were electrically stimulated to induce isometric contractions which resulted in an increase in tracheal pressure; then the tracheal volume was reduced to a rate (velocity) which kept the tracheal pressure constant at a given level (force). The force-velocity curve was hyperbolic. Using Hills equation, we calculated the values of P0 (the maximum force at 10, lo being the trachealis muscle length at which the maximum active tension develops) and Vmax (the maximum velocity at zero afterload). They were P0 = 0.85 +/- 0.20 kg/cm2 and Vmax = 0.08 +/- 0.02 l0/s. We concluded that both force and velocity of the trachealis muscle in situ exhibited lower values than those in vitro.

Effect of sublingual isosorbide dinitrate on sputum volume and viscoelasticity in chronic obstructive lung disease

SummaryThe effect of isosorbide dinitrate (ISDN) on sputum volume and sputum viscoelasticity in 12 patients with chronic obstructive lung diseases (COLD) was investigated by the double-blind randomized cross-over method with matched placebo. Each patient was given either sublingual ISDN 5 mg or placebo at 9 a.m. and sputum was collected for 3 h before and after 9 a. m. The dynamic viscoelasticity of the sputum was measured using a coaxial cylinder rheometer at an angular frequency of 0.1 rad/s. ISDN significantly increased sputum volume, and it caused a significant decrease in dynamic viscosity and in dynamic elasticity compared to placebo. The findings suggest that ISDN might be useful as an expectorant in the treatment of COLD when abundant and viscous sputum is present.