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PubMed1979

Effect of intratracheal and oral application of corticosteroids on the adrenal function test in beagle dogs after ACTH-stimulation.

The effect of synthetic corticosteroids given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test. In addition, histological and morphometrical examinations of the adrenal cortex were performed at the end of the study. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05, 0.1 and 0.5 mg/kg body weight led to a dose dependent adrenal suppression on the basis of plasma cortisol concentration and eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg body weight. Also the oral administration of 0.1 mg/kg body weight/day of beclomethasone dipropionate had a definite adrenal suppressive effect comparaable to that of 0.1 mg/kg body weight given intratracheally. However, intratracheal administration of fluocortin butylester, a local antiinflammatory drug but systemically a nearly ineffective corticosteroid (2 X 8 mg/kg body weight/day) had no suppressive effect on the adrenal gland of the beagle dog, even after a 320 times higher dose.

Administration, Oral↗

PubMed1989

A method for intratracheal instillation of endotoxin into the lungs of mice.

A detailed method is presented for the intratracheal instillation of fluids into the lungs of mice. Using 125I-albumen it was determined that 25-50 microliters of volume gave almost equal distribution to all lobes of the mouse lung. Extremely low levels of endotoxin given intratracheally (12.5-25 ng) resulted in a dramatic increase in the neutrophil content of the lung. The increase started in less than 4 h, reaching levels of 7 x 10(5) by 18 h and was maintained at elevated levels for at least 48 h. This neutrophil count represented more than 90% of the cell population of the lung.

Animals↗

PubMed2001

Tracheal gas insufflation and related techniques to introduce gas flow into the trachea.

Over the past 50 years, a variety of techniques have been developed that have in common the insufflation of gas into the central airway to facilitate carbon dioxide (CO2) clearance. These include continuous insufflation of oxygen, transtracheal jet ventilation, high frequency jet ventilation, transtracheal oxygen administration, intratracheal pulmonary ventilation, and tracheal gas insufflation (TGI). Continuous insufflation of oxygen is a technique used to enhance CO2 removal in the presence of apnea. Transtracheal jet ventilation and high frequency jet ventilation promote bulk gas flow into the lungs. Some techniques, such as transtracheal oxygen administration, provide insufflation of oxygen as an adjunct to spontaneous ventilation. However, other techniques, such as TGI, are used as an adjunct to positive pressure ventilation. Intratracheal pulmonary ventilation provides positive pressure ventilation while bypassing the upper airway. Although some of these techniques are promising adjuncts to mechanical ventilation and may help reduce ventilator-associated lung injury, much remains to be learned about their role in the care of patients with acute lung injury.

Equipment Design↗

PubMed1996

Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis.

OBJECTIVE: To determine the clinical features and optimal treatment of subglottic stenosis (SGS) in patients with-Wegener's granulomatosis (WG). METHODS: Review of 43 patients with SGS and treatment of 20 patients with intratracheal dilation-glucocorticoid injection therapy. RESULTS: SGS developed in 43 of 189 patients with WG who were followed up at the National Institutes of Health Clinical Center. The diagnosis of SGS occurred in the absence of other features of active. WG in 21 of 43 patients (49%). In 21 patients (49%), SGS began while the patient was receiving systemic immunosuppressive therapy for disease activity involving other sites. Tracheostomy was required in 10 of 18 patients (56%) who were treated with systemic immunosuppressive therapy. In 20 patients treated with intratracheal therapy, none required tracheostomy and 6 with previous tracheostomies were decannulated. CONCLUSION: SGS often occurs independently of other features of active WG and is frequently unresponsive to systemic immunosuppressive therapy. Intratracheal dilation-injection therapy provides a safe and effective treatment for WG-associated SGS and, in the absence of major organ disease activity, should be used without concomitant systemic immunosuppressive agents.

Adult↗

PubMed2001

Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse.

It is well recognized that activation of the coagulation system plays an important role in bleomycin (BLM)-induced lung injury and fibrosis. The protein C (PC) pathway is an important regulator of the coagulation system. In this study, we evaluated the bronchoalveolar lavage fluid (BALF) concentration of activated PC (APC) and the therapeutic effect of the intratracheal administration of APC on BLM-induced lung fibrosis in mice. APC levels in BALF were significantly lower in BLM-treated animals than in the saline-treated group. Fibrotic changes were progressive in mice treated with BLM and intratracheal instillation of vehicle (BLM/Veh) after 14 and 21 d of BLM infusion. Compared with the BLM/Veh group, histologic findings on Days 14 and 21 in mice treated with BLM and intratracheal instillation of APC (BLM/APC) showed less fibrotic lesions in the subpleural and central areas of the lung. The mean Aschcroft's fibrosis score in the BLM/Veh group was significantly (p < 0.05) higher than in the BLM/APC group. The lung hydroxyproline content on Day 21 was significantly higher (p < 0.05) in the BLM/Veh group (1.78 +/- 0.07 micromol/lung weight) than in the BLM/APC (1.30 +/- 0.06 micromol/lung weight) group. The ratio of plasminogen activator activity to thrombin level in BALF was significantly increased in the BLM/APC group compared with the BLM/ Veh group on Day 21. The expression of tumor necrosis factor-alpha and interleukin-1beta was significantly decreased in the lungs of the BLM/APC group compared with the BLM/Veh group on Day 14 after BLM infusion. These results showed that intratracheal APC administration inhibits the development of lung fibrosis in BLM-induced lung injury, giving further support to the important role that the PC pathway plays in the mechanism of lung fibrosis.

Animals↗

PubMed1983

A safe, nonflammable, all-metal, cuffless endotracheal Venturi ventilation system for use in laser surgery.

In this preliminary study with seven dogs, ventilation with a Sanders bronchoscope attachment coupled to the Norton metal endotracheal tube and use of a jet O2 injector system proved adequate for sustained oxygenation and acid-base balance. This system is shown to be superior to the conventional anesthesia volume ventilator when used with the cuffless metal endotracheal tube. The ventilatory capability can be easily adjusted upward and downward by changing the driving pressures of the reducing valve. Peak intratracheal and transtracheal pressure measurements show the pressures encountered to be similar to those of conventional volume ventilation techniques. The use of the all-metal endotracheal tube in endolaryngeal laser surgery is discussed. The advantages of such a system lie in the elimination of a flammable endotracheal tube during laser endolaryngeal surgery while preserving adequate and stable ventilation.

Animals↗

PubMed2003

CC chemokine ligand 1 promotes recruitment of eosinophils but not Th2 cells during the development of allergic airways disease.

One of the characteristic features of allergic asthma is recruitment of large numbers of inflammatory cells including eosinophils and Th2 lymphocytes to the lung. This influx of inflammatory cells is thought to be a controlled and coordinated process mediated by chemokines and their receptors. It is thought that distinct, differential expression of chemokine receptors allows selective migration of T cell subtypes in response to the chemokines that bind these receptors. Th2 cells preferentially express CCR8 and migrate selectively to its ligand, CC chemokine ligand (CCL)1. We studied the role of the CCR8 ligand, CCL1, in the specific recruitment of Th2 cells and eosinophils to the lung in a murine model of allergic airway disease. We have demonstrated for the first time that CCL1 is up-regulated in the lung following allergen challenge. Moreover, a neutralizing Ab to CCL1 reduced eosinophil migration to the lung, but had no effect on recruitment of Th2 cells following allergen challenge. In addition, there was no change in airway hyperresponsiveness or levels of Th2 cytokines. In a Th2 cell transfer system of pulmonary inflammation, anti-CCL1 also failed to affect recruitment of Th2 cells to the lung following allergen challenge. Significantly, intratracheal instillation of rCCL1 increased recruitment of eosinophils but not Th2 cells to the lung in allergen-sensitized and -challenged mice. In summary, our results indicate that CCL1 is important for the pulmonary recruitment of eosinophils, rather than allergen-specific Th2 cells, following allergen challenge.

Adoptive Transfer↗

PubMed2005

Use of an inspiratory impedance threshold device on a facemask and endotracheal tube to reduce intrathoracic pressures during the decompression phase of active compression-decompression cardiopulmonary resuscitation.

INTRODUCTION: Use of an inspiratory impedance threshold device (ITD) significantly increases coronary perfusion pressures and survival in patients ventilated with an endotracheal tube (ETT) during active compression-decompression cardiopulmonary resuscitation. We tested the hypothesis that the ITD could lower intratracheal pressures when attached to either a facemask or ETT. METHODS: An active and sham ITD were randomly applied first to a facemask and then to an ETT during active compression-decompression cardiopulmonary resuscitation in 13 out-of-hospital cardiac arrest patients in a randomized, double-blinded, prospective clinical trial. The compression-to-bag-valve ventilation ratio was 15:2. Airway pressures (surrogate for intrathoracic pressure) were measured with a pressure transducer. A sham and an active ITD were used for 1 min each in a randomized order, first on a facemask and then on an ETT. Statistical analyses were made using Friedman's and Wilcoxon's rank-sum tests. RESULTS: For the primary end point, mean +/- sd maximum negative intrathoracic pressures (mm Hg) during the decompression phase of cardiopulmonary resuscitation were -1.0 +/- 0.73 mm Hg with a sham vs. -4.6 +/- 3.7 mm Hg with an active ITD on the facemask (p = .003) and -1.3 +/- 1.3 mm Hg with a sham ITD vs. -7.3 +/- 4.5 mm Hg with an active ITD on an ETT (p = .0009). Decompression phase airway pressures with the facemask and ETT were not statistically different. CONCLUSIONS: Use of an active ITD attached to a facemask or an ETT resulted in a significantly lower negative intratracheal pressure during the decompression phase of active compression-decompression cardiopulmonary resuscitation when compared with controls. Airway pressures with an ITD on either a facemask or ETT were similar. The ITD-facemask combination was practical and enables rapid deployment of this life-saving technology.

Cardiography, Impedance↗

PubMed2001

Altered expression of lung cytochrome P450 3A1 in rat after exposure to sulfur mustard.

Expression of cytochromes P450 (CYP) and glutathione S-transferases in the lung may be affected by inhaled pollutants. We have investigated the effect of sulfur mustard on the expression of CYP 1A1, 2B1, 2E1 and 3A1, as well as of alpha-, micro- and pi-glutathione S-transferases in rat lung. Sulfur mustard (0.025, 0.05 or 0.1 mg/kg) or its vehicle was administered to anaesthetized animals by intratracheal injection. Expression of CYP and glutathione S-transferases was analysed 24 hr after administration of the vesicant warfare using western blotting. Preservation of airway epithelium integrity after animal exposure to sulfur mustard was confirmed by histological examination of tracheal and lung tissues from control and treated animals. Constitutive levels of CYP 2B1 and 3A1 proteins were found in lung tissue from control rats, whereas CYP 1A1 and 2E1 proteins were not detected. Animal exposure to sulfur mustard enhanced CYP 3A1 protein levels by 80 to 103%. In contrast, exposure to sulfur mustard neither modified CYP 2B1 expression, nor led to detectable expression of CYP 1A1 or 2E1. Constitutive levels of alpha-, micro- and pi-glutathione S-transferase proteins were found in lung tissue from control rats. Exposure to sulfur mustard had no effect on expression of either of the glutathione S-transferases. Our results show that intratracheal exposure to sulfur mustard selectively increases CYP 3A1 expression in rat lung. Taking into account the major role of CYP of the 3A family in the metabolism of drugs, up-regulation of CYP 3A1 by sulfur mustard might have important therapeutic consequences.

Animals↗

PubMed1975

Cell-mediated immune responses to transplanted tumors in mice chronically exposed to cigarette smoke.

C57BL and BALB/c mice were exposed to fresh cigarette smoke for 7-8 minutes per day for varying periods up to 30 weeks before subcutaneous or intratracheal inoculation of viable tumor cells. The growth rates of subcutaneous tumors in the mice exposed to smoke were significantly higher than those of controls and more lung metastases were noted. Enhanced tumor growth rates in the respiratory tracts of smoke-exposed mice were evidenced by the markedly increased death rates in these animals after the intratracheal inoculation of tumor cells. Increased tumor growth rates in mice that inhaled smoke were assoicated with depressed tumor-specific cytotoxic responses in both spleens and regional lymph nodes. Short-term exposure (10 wk) of mice to cigarette smoke resulted in decreased tumor growth rates concomitant with enhanced cytotoxic responses.

Animals↗

PubMed1995

A transtracheal catheter for recording the static tracheal pressure in the exercising horse.

After giving an account of the principles of pressure measurement in flowing air and a review of the literature on tracheal catheters, the authors describe the construction, the introduction and the function of their own transtracheal catheter. This is a teflon catheter with several side-ports which is introduced into the cervical trachea by a guide technique. After introduction, the catheter is stiffened by the insertion of 2 steel wires. The catheter was studied in model experiments concerning: a) the ability to measure the static pressure in flowing air, and b) the dynamic accuracy of a recording system built up around the catheter. The results indicated that the intratracheal pressure sensed in exercising horses well reflected the static pressure, and that the dynamic accuracy of the recording system was good to about 60 Hz. The present technique of recording the intratracheal pressure was used on 122 occasions in 69 exercising horses with only one complication referable to the catheter occurring. The transtracheal route of catheterisation may be superior, as catheters introduced by this route do not appear to influence the function of the pharynx and larynx. In contrast, nasotracheal catheters that traverse the larynx, might interfere with the respiratory function.

Airway Resistance↗

PubMed1976

[Tracheotomy-faults and complications].

Complications associated with tracheotomy are reduced by prompt operation when indications develop, by meticulous technical performance of operation and careful postoperative care. The selection of intratracheal tube according to size and form is one measure to reduce both mortality and morbidity. Among the complications are dry hemorrhagic tracheobronchitis with crusts, severe arrosion bleeding and quite frequently secondary tracheal stenosis. In some cases it is more advisable to perform the tracheostomy in which the trachea is brought to the skin and sewed in place-providing a permanent opening.

Adult↗

PubMed1994

Pulmonary retention of free and liposome-encapsulated tobramycin after intratracheal administration in uninfected rats and rats infected with Pseudomonas aeruginosa.

The pulmonary residence time of free and liposome-encapsulated tobramycin was studied with uninfected rats and rats infected with Pseudomonas aeruginosa. Chronic infection in lungs was established by intratracheal administration of 10(8) CFU of P. aeruginosa PA 508 prepared in agar beads. After 3 days, a single dose (300 micrograms) of free or liposome-encapsulated tobramycin was given intratracheally to both infected and uninfected rats. At various time intervals (0.25 to 16 h) after drug instillations, the remaining tobramycin was evaluated in blood, lungs, and kidneys by a microbiological assay. Intratracheal instillation of liposome-encapsulated tobramycin resulted in high and sustained levels of tobramycin in lungs of uninfected and infected rats over the 16-h period studied; however, the tobramycin levels were two times higher in uninfected rats. There was no tobramycin detected in the blood or kidneys from these animals. In contrast, the intratracheally instilled free tobramycin was cleared within 3 and 1 h from the lungs of uninfected and infected animals, respectively. These data suggest that the encapsulation of tobramycin in liposomes can result in a significant increase of its residence time within lungs. This study also shows that pulmonary infection was associated with a lowering of tobramycin levels in lungs.

Animals↗

PubMed1977

Intermittent positive pressure inflation during fiberoptic bronchoscopy.

We describe a new technique for diagnostic fiberoptic bronchoscopic procedures under general anesthesia. The technique of inflation via nasotracheal catheter, which consists of using intermittent high inflating pressure for ventilation by passing a double catheter through the nose to the glottis and into the trachea, gave very satisfactory ventilaton, with high levels of oxygen in the blood. Intratracheal pressure was monitored continuously to guarantee safety, and pulmonary function was assessed before and after the procedure. Continuous electrocardiographic monitoring was used, and blood gas levels were determined at very frequent intervals. The use of infusions of methohexitone and succinylcholine (suxamethonium) provided adequate safe anesthesia and prompt recovery, with absence of recall of the procedure.

Aged↗

PubMed1986

Metabolism of testosterone to 17 beta-hydroxy-5 alpha-androstane-3-one and 5 alpha-androstane-3 alpha, 17 beta-diol in alveolar macrophages from rat lung--II. Effects of intratracheal instillation of 3.4 mumol K2Cr2O7.

Activity of the steroid 5 alpha-reductase in pulmonary alveolar macrophages from adult male rats has been investigated in vitro. Intratracheal instillation of 3.4 mumol K2Cr2O7 lowered the enzyme activity within 6 h, and the reduction was significant on the subsequent 2, 4 and 7 days. The activity of this enzyme was significantly decreased only 6 and 24 h after instillation when measured in the 800 g supernatant fraction of whole lung. Instillation of 3.4 mumol K2Cr2O7 increased serum levels of corticosterone. Serum levels of triiodothyronine and thyroxine decreased except for a transient increase 3 h after the K2Cr2O7 instillation. Subcutaneous administration of 200 micrograms dexamethasone/100 g b.wt, 200 micrograms/100 g b.wt of testosterone, 17 beta-hydroxy-5 alpha-androstane-3-one (5 alpha-DHT), dehydroepiandrosterone or corticosterone had no effect on the 5 alpha-reductase activity of the pulmonary alveolar macrophages within 12 h. The combined treatment with dexamethasone s.c. and intratracheal instillation of 3.4 mumol K2Cr2O7 reduced the steroid 5 alpha-reductase activity in the pulmonary alveolar macrophages to about 25% of controls. Measurement of the steroid 5 alpha-reductase activity in pulmonary alveolar macrophages as an index of lung damage when exposed to toxic material is discussed.

5-alpha Reductase Inhibitors↗

PubMed2004

Local and systemic immune responses to intratracheal instillation of antigen and DNA vaccines in mice.

PURPOSE: The purpose of this study was to determine the immunization efficacy of antigen and DNA vaccines after delivery to the lung, to assess the integrity of the pulmonary tissue after vaccination, and to elucidate mechanisms involved in the induction of immunity. METHODS: Ovalbumin, the plasmid encoding ovalbumin, the hepatitis B surface antigen (HBsAg), or plasmid encoding HBsAg were intratracheally instilled or injected in quadriceps in mice. The immune response and its Th polarization were analyzed over time. Markers of inflammation were measured in bronchoalveolar lavage, and lung histology was performed. The fate of ovalbumin following intratracheal instillation was studied. RESULTS: According to the vaccine, the pulmonary route produced stronger or equivalent humoral and cellular responses systemically and locally in the lung as compared to injection. The IgG subclasses and cytokine pattern indicate that the immunity was preferentially polarized toward the Th2 and Th1 type for antigen and DNA immunization, respectively. Ovalbumin penetrated the respiratory tissue and blood poorly after intratracheal instillation, suggesting that the immune response was triggered at airway surfaces. Overall, vaccines delivered to the lung did not induce any local sign of inflammation. CONCLUSIONS: Pulmonary administration of vaccines might be a promising alternative to conventional vaccination by injection.

Animals↗

PubMed2002

Pharmacokinetics and efficacies of liposomal and conventional formulations of tobramycin after intratracheal administration in rats with pulmonary Burkholderia cepacia infection.

The objective of the present study was to determine the pharmacokinetics and efficacies of liposomal and conventional formulations of tobramycin against Burkholderia cepacia in a model of chronic lung infection. Male Sprague-Dawley rats were inoculated intratracheally with 10(6) CFU of a very resistant strain of B. cepacia (strain BC 1368; MIC, 128 micro g/ml) to establish lung infection. A 1,200- micro g dose of tobramycin was administered intratracheally as a liposomal formulation and as a conventional formulation. Rats were anesthetized and exsanguinated by cardiac puncture at different times over 24 h to assess pulmonary tobramycin concentrations and the number of residual CFU. Pharmacokinetic parameters were calculated by using a two-compartment model with NONMEM. The mean half-life at the beta phase (t(1/2beta)) and the pulmonary exposure (the area under the concentration-time curve [AUC]) of liposomal tobramycin were 19.7 h (coefficient of variation [CV], 24.2%) and 6,811 micro g. h/lungs (CV, 19.7%), respectively. The pharmacokinetics of conventional tobramycin were statistically different, with a t(1/2beta) and AUC of 12.9 h (CV, 31.4%) and 821 micro g. h/lungs (CV, 15.0%), respectively. Pearson chi-square analyses were performed on residual CFU data distributed in the following categories: <10(3), 10(3) to 10(5), and >10(5). Differences in CFU data between formulations showed a statistical trend (P < 0.10) when data from all time points were used, and statistically significant differences were found after 12 h (P < 0.05), with greater eradication achieved with the liposomal formulation. In conclusion, intratracheal administration of tobramycin in liposomes was associated with marked changes in the pharmacokinetics of the drug in the lung and an apparent trend for a prolonged efficacy against B. cepacia. These results support the hypothesis that inhalation of liposomal tobramycin may improve the management of chronic pulmonary infections caused by resistant bacteria in patients with cystic fibrosis.

Animals↗

PubMed1994

Prevention of gram negative nosocomial bronchopneumonia by intratracheal colistin in critically ill patients. Histologic and bacteriologic study.

OBJECTIVE: To evaluate the efficiency of intratracheal colistin in preventing nosocomial bronchopneumonia (BPN) in the critically ill. DESIGN: Study evaluating the clinical incidence of nosocomial BPN in 2 groups of critically ill patients who receive or did not receive intratracheal colistin. BPN was assessed clinically in survivors and histologically in non-survivors. SETTING: A 14-bed surgical intensive care unit. PATIENTS: 598 consecutive critically ill patients were studied during a prospective non-randomized study over a 40-month period. INTERVENTIONS: 251 patients--31 non-survivors and 220 survivors--did not receive intratracheal colistin and 347-42 non-survivors and 305 survivors--received intratracheal colistin for a 2-week period (1,600,000 units per 24 h). MEASUREMENTS AND RESULTS: The incidence of nosocomial BPN was evaluated clinically in survivors, using repeated protected minibronchoalveolar lavages, and histologically in non-survivors via an immediate postmortem pneumonectomy (histologic and semi-quantitative bacteriologic analysis of one lung). The clinical incidence of nosocomial BPN was of 37% in coli (-) survivors and of 27% in coli (+) survivors (p < 0.01). This result was histologically confirmed in non-survivors, where the incidence of histologic BPN was of 61% in coli (-) patients and of 36% in coli (+) patients (p < 0.001). Emergence of BPN due to colistin-resistant micro-organisms was not observed. Because colistin was successful in preventing Gram-negative BPN and did not change the absolute number of Gram-positive BPN, the proportion of BPN caused by staphylococcus species was higher in group coli (+) patients (33% vs 16%). Mortality was not significantly influenced by the administration of colistin. CONCLUSION: This study suggests that the administration of intratracheal colistin during a 2-week period significantly reduces the incidence of Gram-negative BPN without creating an increasing number of BPN due to colistin-resistant micro-organisms.

Aged↗