Reconstructive tracheobronchial surgery has become routine as a function-preservative method. Its applications have gradually expanded from the treatment of strictures induced by inflammation and trauma to the treatment of malignant tumors. Reconstructive surgery is regarded of great significance especially for patients with lung cancer, since the pulmonary function deteriorates rapidly with age. Our aim is for successful transplantation of the lung for the treatment of respiratory insufficiency. We consider reconstructive surgery of the bronchus to be a prior stage to lung transplantation. In our institute, reconstructive surgery of the bronchus was performed on 73 patients consisting of 12 with stricture due to inflammation or trauma and 61 (83.6%) with tumor. This amounts to only 5.4% of a total of 1, 140 resected cases of lung cancer. Of supreme importance on technical requirements are prevention of postoperative fistula and stricture due to granulation or scarring and prevention of tumor recurrence at the site of anastomosis. Sutures should be spaced rather widely apart, placed deeply through all layers using a synthetic absorbable suture. It is also important to dissect the bronchus at the bifurcation so that the side with the narrow aperture has a larger diameter to be pulled up to and anastomosed with the side with the wider aperture. This inevitably necessitates as large a dissection of the bronchus as possible. Of malignant tumors treated by reconstructive surgery, 46(79%) were squamous cell carcinoma. The five-year survival rate of patients treated for lung cancer by reconstructive surgery was 67% in stages I and II and 7.9% in stage III. The average rate was 37% and this exceeded the results obtained in our institute for lung resection in general. Our reconstruction cases included 9 which underwent sleeve lobectomy with pulmonary artery reconstruction for bronchogenic carcinoma. With the exception of 2 who are still alive at 26 months and 6 months respectively, all died of recurrence. Reconstruction of the pulmonary artery had been limited only to lengths of less than 2 cm and the above cases should have been categorized as cases of infiltration into adjacent organs. At present we consider that this type of case should have been managed by pneumonectomy and adequate dissection of the hilar and mediastinal lymph nodes. Our reconstructive surgeries also included 8 cases of carina reconstruction which were all approached by ipsilateral thoracotomy. Although denervation is known to affect the pulmonary vasculature, air-way system, cough reflex and respiratory regulation postoperatively, it should not cause serious complications. Surgery would be futile if ablation and lymph node dissection were performed incompletely to preserve the vagus nerve in the lung. It should be emphasized that postoperative depression of pulmonary function does not result directly from denervation but is rather caused by stricture as a result of sclerotic changes of the granulation tissue occurring in periphery of the anastomosis site. We intend to continue every effort in successful transplantation of the lung and artificial organs. Relief of pain and prolongation of life are no doubt very important, but future therapeutic strategies must also aim to preserve physical functions so that the patients may return to a normal life.

View full abstract

The histological and electron microscopic structures of the tracheo-bronchial glands and cells of humans and some other mammals are discussed. Histochemical studies revealed that the glands play an important role in the defense mechanism of the tracheo-bronchial system to secret mucous and serous substances. The mucous contributes the defense mechanism against mechanical injuries, while on the other hand, the serous substances play biochemical and immunological role against extrinsic noxious substances and germs in the respiratory tract. An animal experiment showed that the gland regenerates accompanied by regeneration of surface epithelium of the trachea after mechanical injuries. Histochemical and electron microscopic observation suggested that the bronchial glands might play an important role in the oncogenesis of some adenocarcinomas of the lung.

View full abstract

Transbronchial lung biopsy (TBLB) was performed in 299 patients with abnormal chest shadows in our department over the past 4 years in order to obtain a definitive diagnosis. The patients were classified into 3 groups depending upon the roentgenological findings : 1) Tumor shadow -142 cases. 2) Focal infiltration -97 cases. 3) Diffuse shadow -60 cases. A definite or almost definite diagnosis (in inflammatory desease cases) was obtained in 254 of 299 cases (84.9%). The diagnostic accuracy of TBLB in the 3 groups was as follows. : (1) Tumor shadow 85.2% (121/141) (2) Focal infiltration 82.5% (80/97) (3) Diffuse shadow 88.3% (53/60) There was no significant difference in the diagnostic ratios in the 3 groups. A specific definitive diagnosis was obtained in 149 of 299 cases (49.8%) by TBLB. The diagnostic accuracy of TBLB in the 3 groups was 69.7% (99/142), 26.8% (26/97) and 40% (24/60), respectively. Significant differences were noted in the definitive diagnostic ratios of the 3 groups. Complications were noted in 10 cases, moderate or massive bleeding in 6 cases, and pneumothorax in 4 cases.

View full abstract

In order to investigate the applications and diagnostic effectiveness of TBLB, cases of diffuse pulmonary diseases in which TBLB was performed between in January 1980 and December 1984 were reviewed. These totalled 132 cases and included idiopathic interstitial pneumonia (43 cases), sarcoidosis (33 cases), hypersensitivity pneumonitis (22 cases) and diffuse panbronchiolitis (19 cases). A diagnosis was obtained in 69.7% of idiopathic interstitial pneumonia, 57.6% of sarcoidosis (36.1% in Stage I, 81.8% in Stage II and 100% in Stage III), 90.1% of hypersensitivity pneumonitis and 57.9% of diffuse panbronchiolitis. The diagnostic effectiveness was higher in sarcoidosis and hypersensitivity pneumonitis, both of which have specific findings histologically, proving the usefulness of TBLB. In contrast, the effectiveness was comparatively lower in idiopathic interstitial pneumonia and in diffuse panbronchiolitis due to the low histological specificity of these diseases and to the difficulty of obtaining satisfactory specimens. Mean numbers of specimens were 4.1 from idiopathic interstitial pneumonia, 3.5 from sarcoidosis, 3.6 from hypersensitive pneumonitis and 3.4 from diffuse panbronchiolitis. A suitable number of specimens for diagnosis would be 4 in view of preventing complications due to TBLB.

View full abstract

We performed transbronchial lung biopsy (TBLB) in 273 patients with diffuse pulmonary disease from Sep 1977 to Dec 1984 and histological confirmation of the clinical diagnosis was made in 185 patients (68%). Compared to open lung biopsy, the most attractive feature of TBLB is its repeatability. Especially in interstitial lung disease, the major purposes of the lung biopsy are not only confirmation of the diagnosis but assessment of disease activity. From this viewpoint, repeated TBLB yields chronological information about histological changes during follow-up of the clinical course. In this paper, the results of three cases of interstitial lung disease followed up by repeated TBLB were presented. Case 1 was a typical case of idiopathic pulmonary fibrosis. Histological findings obtained from two TBLB procedures showed some improvement of alveolitis after steroid therapy, but progression of fibrosis with histological destruction was also noted in other portions of the biopsy specimens. Case 2 was a case of hypersensitivity pneumonitis. Repeated TBLB confirmed the almost complete resolution of the alveolitis and intra-alveolar granulomatous exudate. Recurrence of the disease the following year, histological confirmation by TBLB and positive provocation test established the diagnosis. Case 3 was a possible case of mixed type pneumonia. Biopsy specimens showed alveolitis with inflammatory cell infiltrate and obliteration of the alveolar ducts to respiratory bronchioles by organized exudate. The findings of 3 TBLB procedures showed marked improvement of the lesions after steroid therapy, but patchy residual of minor degree alveolitis was also observed. Chronological information concerning pathological changes obtained from TBLB may provide new insights into the pathogenesis of diffuse pulmonary disease, and in order to obtain fruitful results, close cooperation between clinicians and pathologists should be emphasized.

View full abstract

The results of TBLB in 25 patients with acute respiratory failure, most of whom were on artificial ventilation, are described. TBLB had a definitive diagnostic yield of 28% (7 of 25 cases) and a probable diagnosis was obtained in 12% (3 of 25 cases). In 12 other patients, findings of TBLB were non-specific but were helpful in deciding on effective treatment. The findings of TBLB were relatively compatible in comparison with the findings of the lungs at autopsy in 7 cases. Major complications occurred in 9 of 27 TBLB procedures (33%) (barotrauma in 5, moderate bleeding is 4), and 2 patients required insertion of a chest tube because of tension pneumothorax. The TBLB can be valuable for evaluation of pulmonary disease in acute respiratory failure, if the procedure is undertaken under careful observation and preparations are made for serious complications.

View full abstract

In order to establish an early diagnosis, transbronchial lung biopsy (TBLB) was performed in the patients with pulmonary infections, especially in cases in which sputum smear was negative for pulmonary tuberculosis, pulmonary mycosis and Pneumocystis carinii pneumonia. In 57 cases in which sputum smears were negative for pulmonary tuberculosis, findnigs suggesting tuberculosis, were obtained in 33 cases (57.9%). By additional tests such as intrabronchial sputum aspiration or bacteriological examination of expectorated sputum following TBLB, a rapid diagnosis was made in a total of 38 cases (66.7%). In pulmonary mycotic infection, a pathological diagnosis by means of TBLB was obtained in 11 out of 12 cases (91.7%) with pulmonary cryptococcosis and in 2 out of 3 cases (66.7%) with pulmonary aspergiloma, therefore TBLB is more effective examination than intrabronchial sputum aspiration or expectorated sputum examinations in these cases. In the six fiberoptic examinations of pneumocystis carinii pneumonia, TBLB was performed in three cases and BAL in five cases. Pneumocystis carinii were demonstrated by Grocott's stain in all samples. TBLB and/or BAL were considered to be useful examinations for diagnosis of Pneumocystis carinii pneumonia. In conclusion, TBLB was useful in making a rapid diagnosis of cases in which sputum smears were negative for pulmonary tuberculosis, pulmonary mycosis and pneumocystis carinii pneumonia. Examinations such as intrabronchial sputum aspiration, expectorated sputum examination following TBLB, and/or BAL yielded higher diagnosis rates in pulmonary infections.

View full abstract

Ultrastructure of epithelial cell which are distributed on airway and alveolar wall, and also the surface lining layer (surfactant=Sf) of the lung were observed by using scanning and transmission electron microscope. The central area of the airway is consisted of five kinds of epithelium ; ciliated cell with excrete function, goblet cell with exocrine function, neuroendocrine cell (chemoreceptor), intermediate cell and basal cell (reserve cell). Moreover, this area possesses tracheo-bronchial glands. Peripheral area of the airway is consisted of only two kinds of epithelium, namely, immature ciliated cell and Clara cell which seems to posses metabolic function of phospholipid such as Sf. In the respiratory bronchioles, there is structure like alveolus which is covered with type I alveolar epithelium (gas-exchange) and type II alveolar epithelium. Those alveolus like structure have same function as peripheral alveolus. In the alveolar area, air-blood barrier is formed as a functional structure which is composed of type I alveolar epithelium playing an important role in the gas-exchange and type II alveolar epithelium which secretes Sf and serves as reserve cell of type I epithelium. Due to function of goblet cells and presence of tracheo-bronchial glands in the central area of the air way, relatively large amount of liquid component is found in this area. Whereas only a small amount of liquid component is found in the peripheral airway and alveolus. Every airway and alveolar area is covered by Sf-membrane which forms air-liquid interface and this Sf-membrane is the first line of lung defense mechanism. Surface lining layer with Sf-membrane is indirectly pulled up to the central area of airway in an escalator-like manner by the combination mechanisms of continuous secretion of Sf, surface diffusion capacity of Sf and the ciliary movement into the central area. It is suggested that the initial part of defense mechanisms of the airway-alveolus is maintained by the above phenomenon.

View full abstract

Both visualization and quantification of the mucociliary clearance mechanisms in human ciliated airways in vivo have become possible by means of radioaerosol inhalation lung cine-scintigraphy. The development of this new research and clinical method to evaluate mucociliary clearance mechanisms was briefly described with reference to methods to evaluate the mucociliary clearance mechanisms in health and disease both visually and qualitatively. Mucociliary clearance mechanisms in chronic obstructive pulmonary disease, lung cancer, bronchiectasis, pulmonary fibrosis etc. were described. For quantitative evaluation we have defined the following 5 indices : lung retention ratio, airway deposition ratio, airway retention ratio, airway clearance efficiency and alveolar deposition ratio. Both 2'hrs continuous measurement of radioactivity in the thorax following aerosol inhalation and a repeat measurement at 24 hrs were essential in our original method, but this was simplified to only 1-hr initial measurement of radioactivity without repeating it at 24hrs. In the proposed regression equation only lung retention ratio at 60 min (LRR_<60>) and FEV_<1.0%> were required to calculate the alveolar deposition ratio. The simplified method has been more practical clinically.

View full abstract

We estimated alveolar epithelial permeability in patients with interstitial lung diseases and assessed the clinical significance of the measurement. ^<99m>Tc-DTPA (diethylene triamine penta acetate) aerosol was inhaled while breathing normally for five minutes. The anterior chest was sequentially imaged by a gamma-camera for 25 minutes. We assumed the alveolar lining layer to be a single compartment concerning efflux of ^<99m>Tc-DTPA. Clearance of ^<99m>Tc-DTPA from the layer was represented by a rate constant "kep" as a parameter for the permeability of alveolar epithelium. Healthy subjects showed neither a sex difference in kep value nor a correlation between kep and age. In patients with radiation pneumonitis the mean kep value for the area with infiltration on the chest X-ray was 29.9 12.3=10^<i3>min^<i1> and it was significantly greater than the kep of 12.3 4.2=10^<i3>min^<i1> for the area without infiltration. The mean kep in idiopathic interstitial lung disease was 29.1 11.5=10^<i3>min^<i1>, in miscellaneous interstitial lung diseases 28.8 14.1=10^<i3>min^<i1> and sarcoidosis 14.2 4.9=10^<i3>min^<i1>, respectively. One patient with radiation pneumonitis who was studied prospectively showed an abnormal kep value one week before overt abnormalities appeared in either the chest X-ray or the blood gas analysis. This method enables us to detect alveolar epithelial damage in patients with interstitial lung diseases in terms of increased permeability by ^<99m>Tc-DTPA.

View full abstract

Pulmonary alveolar macrophages (PAMs) may play an important role in the clearance of inhaled foreign substances from alveolar spaces. We studied the mechanisms of the disposal of foreign substances by PAM that were obtained from rabbit lungs and human lungs of smokers. When opsonized or nonopsonized yeasts were introduced into the trachea of normal or immunized rabbits, yeasts immunologically binding to PAM membrane receptors were cleared efficiently. To clarify the mechanisms of intracellular disposal of foreign substances by PAMs superoxide production in phagosomes and phago-lysosome fusion were studied. These functions of PAMs differed according to the various properties of phagocytized substances. Especially, specific antibody played an important role in the clearance of live yeasts. We studied how human PAMs deal with deposits of smoking associated substances, and showed that PAMs in bronchoalveolar lavage fluids from smokers increased β-galactosidase activity and superoxide production. Especially, increased numbers of PAM and β-galactosidase activity correlated well with the smoking index (pack years) and duration of smoking. Therefore, these can be used as a marker of biological clearance in alveolar spaces.

View full abstract

In order to clarify complications associated with fiberoptic bronchoscopy, we sent questionnaires to 1, 028 large hospitals in Japan and received 495 replies. The numbers of procedures were 47, 744 cases per year with an accumulate total of 279, 280 cases. Complications were reported in 1, 381 cases (0.49%). Major complications consisted of 611 cases (0.219%) of pneumothorax, 169 cases (0.061%) of xylocaine intoxication, 137 cases (0.049%) of hemorrhage estimated as greater than 300ml, 125 cases (0.045%) of high fever, 57 cases (0.020%) of respiratory arrest, 53 cases (0.019%) of extrasystole, 41 cases (0.015%) of xylocaine shock, 39 cases (0.014%) of a decrease in blood pressure, 34 cases (0.012%) of death and 20 cases (0.007%) of pneumonia. The direct causes of death were 18 cases of hemorrhage (52.9%), 4 cases of pneumothorax (11.8%), 3 cases of respiratory insufficiency (8.8%), 2 cases of circulatory insufficiency and xylocaine shock (5.9%) and 5 cases (14.7%) in which the cause was not recorded on the questionnaire.

View full abstract

In our department cases of severe complications or death have not occurred in more than 14 years using bronchofiberscopes. Bronchofiberscopy is a safe examination if performed with care, but it requires sufficient skill in the prevention of complications and measures to cope with them. The purposes of bronchoscopy performed in 1, 506 cases in the five years from 1980 to 1984 were diagnosis (92.1%) and treatment (7.9%). General anesthesia was performed in 1.7% of these cases and local anesthesia in 98.3%. The main complications due to bronchoscopy and their incidence at this institution were moderate or massive hemorrhage (3.5%) and pneumothorax (0.5%). No cases of death, sequelae, infection or xylocaine shock occured. Prophylaxis and preventive measures : Routine tests are performed after admission. Xylocaine shock : A small amount of xylocaine is sprinkled at the base of the tongue and conditions are observed for several minutes. All drugs and instruments for intubation anesthesia and first aid are provided in the examination room. Cardiopulmonary dysfunction : Blood pressure and pulse are monitored till the end of the examination. Oxygen inhalation, heart monitoring and drip infusion are performed in problematic cases. Airway hemorrhage : Blood tests and coagulation tests are performed before all biopsy procedure. Bosmin or Thrombin is sprayed in advance on the surface of biopsy sites in cases with coagulative abnormality. To cope with hemorrhage in peripheral lesion biopsy, Thrombin is infused through a narrow catheter. In case of massive hemorrhage, an occlusion balloon catheter (MEDI-TECH) is inserted to the target site for occlusion and Thrombin is infused through the catheter to the peripheral lesion. No cases have so far required blood transfusion because of difficulty in hemostasis. Pneumothorax : TBLB can cause hemorrhage and pneumothorax. The target site is confirmed fluoroscopically to avoid a site immediately under the pleura. Chest X-ray examinations are conducted one hour and one day after the procedure. Drainage has not been required in any cases. Pyrexia : Care is taken concerning the maintenance and washing of the instruments. Antibiotics and expectorants are administered after the procedure. Infection : The instruments are washed with water immediately after use, then disinfected with Hibitane. Cydex is used against tubercle bacilli and hepatitis viruses. Protection of persons engaged in the examination from infection and radiation is also important.

View full abstract

Forty six adult patients were monitored with a transcutaneous oxygen tension sensor during fiberoptic bronchoscopy. 1) The transcutaneous oxygen tension values accurately reflected the trends of arterial oxygen tension (r=0.88, n=58, PaO_2=1.11 (PtcO_2)+15.2P<0.001). 2) All procedures except tube intubation showed a reduction in PtcO_2 change rates. PtcO_2 declined remarkably, and approximately to the same extent during biopsy and YAG laser therapy. 3) The average decrease in transcutaneous oxygen tension in all cases of fiberoptic bronchoscopy was 26%. 4) The average decrease in cases over 70 years of age was less than in those under 70 years of age. The transcutaneous oxygen tension monitor provided a continuous assessment of the patient's oxygenation, and gave early warning of potentially hazardous hypoxia and was a highly useful instrument during fiberoptic bronchoscopy, providing increased safety in a group of patients with severely impaired pulmonary and cardiac function.

View full abstract

To evaluate the occurrence of cardiac complications during and after bronchofiberscopic examination in relation to hypoxemia, we prospectively studied 80 patients who underwent bronchofiberscopy with ECG monitoring with a continuous ECG recorder and measurement of arterial blood gases. Arterial oxygen tension dropped during and after bronchofiberscopy. Major complications developed frequently in patients whose initial PaO_2 was less than 60torr breathing room air and without sufficient supplemental oxygen during bronchofiberscopy. However no major complications occurred in patients with supplement oxygen via a side-arm adaptor. Patients with evidence of coronary arterial disease were at high risk for developing major complications. It was recommended that patients with an initial PaO_2 of less than 60torr should receive sufficient supplemental oxygen and those with cardiovascular disease should be monitored electrocardiographically.

View full abstract

Hemorrhage is the most common, and sometimes fatal, complication associated with bronchoscopy and high energy laser treatment. Out of 1263 patients who underwent bronchoscopy during the past 3 years (1982-1984) at our facility, 75 cases (5.9%) exhibited moderate or severe hemorrage which required hemostatic procedures. Although the hemorrage was persistent in 19 cases of these patients, it could be controlled by conservative treatment in all patients. Laser vaporization was performed 121 times in 51 patients during a period of 4 years and 5 months since January, 1981. The treatment involved the trachea alone in 20 of the patients and the bifurcation and/or bronchi in 31. Hemorrhage prevented continuation of vaporization in 5 of the former group and 3 of the latter. Tracheal intubation was maintained to control the hemorrhage as well as to secure the airway in 4 of the former and 2 of the latter. The maintained tracheal tube in patients with tracheal tumors compressed the lesions and facilitated the maintenance of the airway during resumed laser treatment. We experienced as case of massive hemorrhage of the airway during laser vaporization but it was effectively controlled. This paper also provides detailed description of this case.

View full abstract

In smooth muscle cells, the contraction-relaxation cycle is largely dependent on the regulation of ionized free calcium in the cytoplasm, as in the case of skeletal or cardiac muscles, and the sources of Ca^<2+> contributing to the activation of contractile proteins are of extra-and intracellular origins. In an attempt to elucidate the mechanisms involved in the Ca-economy in airway smooth muscle cells, we performed electrophysiological and biochemical experiments using dog or cat tracheal smooth muscle cells. The tracheal smooth muscle cells showed little spontaneous mechanical activity and were electrically quiescent. Application of outward current pulses to the smooth muscle cells did not evoke an action potentioal in normal Krebs solution, however it evoked contractions when the membrane depolarization exceeded 10mV. The amplitude of the contraction increased in proportion to the amplitude of membrane depolarization. Single field stimulation of short duration (50μsec) evoked an excitatory junction potential (e.j.p.) due to acetylcholine released from the vagus nerve terminal, followed by a twitch contraction. The minimum membrane depolarization of e.j.p. to evoke contraction was in the range between 3 to 5 mV, indicating that the membrane depolarization evoked by e.j.p. was more effective in inducing tension development than that induced by the outward current pulses. Amplitudes of contractions evoked by exogenous ACh (10^<i^5>M) were much larger than those evoked by 128 mM-[K]_0 or caffeine (10 mM). In Ca^<2+>-free EGTA (2 mM)-containing solution, the contraction induced by excess-[K]_0 was rapidly abolished, whereas the contractions evoked by ACh were largely unaffected, indicating that the amount of Ca^<2+> stored in the smooth muscle cells of the cat trachea may be larger than other visceral smooth muscle and plays an important role in the initiation of contraction, in response to endogenous or exogenous ACh. The signalling system between the surface membrane (the location of muscarinic ACh receptors) and the intracellular Ca stores is unknown. Recent studies have shown that inositol-trisphosphate (Ins-P_3) may play a physiological role as a second messenger in the mobilization of intracellular Ca^<2+> in different cell types. We have examined the effects of Ins-P_3 on the stored Ca^<2+> of tracheal smooth muscle cells made permeable with saponin to allow the metabolite access to the intracellular Ca^<2+> storage sites. Ins-P_3 (>0.1μM) released the Ca^<2+> accumulated by ATP, in a dose-dependent manner, and about 40% of the total Ca^<2+> was released following application of 3μM Ins-P_3. Application of ACh (10^<i^5>M) to the tracheal tissue stimulated the production of Ins-P_3 in the water soluble fraction and 10s after the application, the relative amount of Ins-P_3 was 290% of the control value. Concomitantly, ACh (10^<i^5>M) either reduced or increased the contents of phosphatidyl inositol 4, 5-biphosphate (Pl-P_2) or phosphatidic acid (PA) in the lipid fraction of the smooth muscle cells to 60% or to 350% of the control value, respectively, thereby indicating that ACh stimulates the phosphodiesteric hydrolysis of Pl-P_2. 5-hydroxytryptamine (5-HT) also reduced or increased the contents of Pl-P_2 or PA to 80 or to 200% of the control value. However neither histamine nor PGF_<2α> showed any effect on the contents of Pl-P_2 or PA in the lipid fraction of the smooth muscle cells. These results indicate that in the tracheal tissue, Ins-P_3 may play the role of intracellular second messenger in the initiation of ACh or 5-HT-induced contraction, but not in the case of histamine or PGF_<2α>-induced contraction.

View full abstract

We have already reported that the beta-adrenergic response of sensitized guinea pig trachea to isoproterenol (ISP) significantly decreased after anaphylaxis in vitro. In addition, we found that the effects of forskolin, which activates adnylate cyclase without stimulation of beta-adrenoceptors, also decreased after anaphylaxis. In this experiment, the effects of anaphylaxis on beta-adrenoceptors were studied as follows : (1) measurement of the number of beta-adrenoceptors on guinea pig lung membrane exposed to antigen (ovalbumin) for one hour by using (-)^<125> l-cyanopindolol (ICYP), (2) measurement of the affinities of ISP to beta-adrenoceptors on lung membrane by an inhibition study. The numbers of beta-adrenceptors and dissociation constants of antigen-exposed lungs measured by using ICYP showed no differences compared with the control. The affinities of ISP to beta-adrenoceptors showed a tendency to decrease in antigen-exposed lungs. Taken together, not only beta-adrenoceptors but also GTP-regulatory protein and adenylate cyclase seemed to be involved in decreased response to ISP after anaphylaxis. These results might partly explain why the effects of beta-adrenergic mimetics decrease in patients with asthmatic attacks.

View full abstract

To determine whether thromboxane A_2 may be involved in ozone-induced airway hyperrespon-siveness, we studied the effect of a thromboxane synthetase inhibitor (OKY-046, 100μg/kg/min, i.v.) in 5 dogs exposed to ozone. Airway responsiveness was assessed by determining the provocative concentration of acetylcholine aerosol that increased total pulmonary resistance by 5 cm H_2O/L/s. Ozone (3 ppm) increased airway responsiveness as demonstrated by a decrease in acetylcholine provocative concentration from 2.42 mg/ml (GSEM, 1.56) to 0.14 mg/ml (GSEM, 1.16). OKY-046 significantly inhibited this effect without altering pre-ozone responsiveness or the ozone-induced increase in neutrophils and airway epithelial cells in bronchoalveolar lavage fluid. To further examine the role of thromboxane A_2, we studied the effect of a thromboxane A_2 mimetic, U-46619, on airway responsiveness in 5 additional dogs. U-46619 in subthreshold doses (i.e., insufficient to increase baseline pulmonary resistance) caused a 4-fold increase in airway responsiveness to acetylcholine. Subthreshold doses of histamine had no effect. These results suggest that thromboxane A_2 may be an important mediator of ozone-induced airway hyperresponsiveness.

View full abstract

Human and guinea-pig tracheal muscle have spontaneous muscle tones in normal Krebs solution. The spontaneous tone in the guinea-pig tracheal muscle was little affected by FPL 55712 (1μM), but completely abolished by indomethacin (1μM), supporting the assumption that muscle tone is maintained by endogenous prostaglandins. On the other hand, in the human tracheal muscle, spontaneous tone was completely suppressed by FPL 55712 (1μM), but potentiated by indomethacin (1μM). It is suggested that leukotrienes are involved in generation of the spontaneous tone and that intrinsic prostaglandins may act as the relaxants in the human tracheal muscle. The contraction induced by excess K^+ in the human tracheal muscle was less affected by verapamil than that in the guinea-pig tracheal muscle. In the presence of high K^+ or stimulant drugs, sensitivity to external Ca^<2+> was higher in the guinea-pig tracheal muscle than taenia coli, and the inhibitory effects of verapamil on the contractions produced by external Ca^<2+> were less in the tracheal than taenia coli, Thus, it is considered that the suppressive effect of Ca^<2+> channel inhibitors such as verapamil might be determined by the relative affinity of Ca^<2+> and Ca^<2+> channel inhibitors for Ca^<2+> pathways, and that the relative affinity may vary from tissue to tissue.

View full abstract