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PubMed1997

Aerosolized surfactant inhibits acetylcholine-induced airway obstruction in rats.

Exogenous surfactant treatment inhibits antigen-induced airway obstruction in sensitized guinea-pigs. Aerosolized surfactant also improves respiratory function in asthmatic patients. The aim of the present study was to determine whether aerosolized surfactant inhibits nonallergic airway obstruction induced by acetylcholine. Anaesthetized Wistar rats were treated by aerosol with the beta2-adrenoceptor agonist terbutaline, surfactant (Alveofact), a surfactant-terbutaline combination, or vehicle (control). Animals were then challenged by aerosolized acetylcholine to elicit receptor-mediated airway obstruction. A second group of animals was challenged with intravenous acetylcholine. Respiratory function variables were measured by body plethysmography before and after treatment, and after the acetylcholine challenge. Baseline lung function values before and after treatment were similar in all groups. Acetylcholine challenge by aerosol increased lung resistance by 64% in control animals. Pretreatment with terbutaline and surfactant significantly limited the increase of lung resistance to +36 and +34%, respectively. Simultaneous aerosolization of surfactant and terbutaline also inhibited airway obstruction but their effects were not additive. By contrast, terbutaline treatment inhibited the effects of intravenous acetylcholine, but surfactant did not. In conclusion, we suggest that surfactant aerosol may prevent acetylcholine and other pharmacological agents from reaching the airway smooth muscle from the airway lumen but not via the bloodstream.

Acetylcholine↗
PubMed1998

New aerosol drug delivery systems for the treatment of immune-mediated pulmonary diseases.

In the lung, unchecked immune responses mediated predominantly by T-lymphocytes and concurrent inflammation can lead to the development of different pathological conditions such as parenchymal disease, interstitial fibrosis, hypersensitivity pneumonitis, bronchiolitis obliterans and bronchiolar asthma. Targeted modulation of uncontrolled T-cell activation and inhibition of cytokine production within different pulmonary compartments is the challenge for the development of novel methods for immunotherapeutic intervention. Utilization of aerosol technology for pulmonary drug delivery represents new potential opportunities for therapeutic application for such immune-mediated pulmonary diseases. For targeted aerosol pulmonary drug delivery, continuous-flow jet nebulizers have several advantages over metered dose or dry powder inhalers since they are the simplest and most effective for aerosol droplet deposition into the peripheral lung tissues. At the present, the major limitations for targeted pulmonary immunosuppression through effective utilization of nebulizer technology has been the conspicuous lack of suitable formulations. The development of liposomal formulations compatible with aerosol delivery with jet nebulizers has expanded the potential for more effective utilization with an array of potent and effective immunosuppressive drugs. For pulmonary therapy, the utilization of liposomes for aerosol delivery has many potential advantages, including universal carrier suitability for most lipophilic drugs, aqueous compatibility, sustained pulmonary release or depot and intracellular delivery. Drug liposomes may also prevent local irritation in the lung, and increase potency with reduced systemic toxicity. Successful utilization of potent immunosuppressive drugs, like cyclosporin, tacrolimus (FK-506), rapamycin, mycophenolate and budesonide, in a variety of immunopathological conditions for other indications demonstrates their potential efficacy for the treatment of many different immune-mediated pulmonary diseases. The route of delivery to the pulmonary tissues can potentially limit adverse effects and markedly affect localized immunosuppressive activity in the lung. Combination of liposomal formulations with topical aerosol delivery to the central and peripheral lung tissues has expanded potential for more effective utilization with these lipophilic immunosuppressive (and antiinflammatory) drugs. Synergistic combinations can also be developed for localized and sustained delivery of therapeutic drug concentrations within the lung to provide multisite immunosuppression. Drug liposome aerosol technology represents one readily available approach for more effective therapeutic intervention in the lung using cyclosporin, FK-506, rapamycin, mycophenolate, budesonide and other lipophilic drugs.

Journal Article↗
PubMed2003

Retrieval of stratospheric aerosol size and composition information from solar infrared transmission spectra.

Infrared transmission spectra were recorded by the Jet Propulsion Laboratory MkIV interferometer during flights aboard the NASA DC-8 aircraft as part of the Airborne Arctic Stratospheric Expedition II (AASE II) mission in the early months of 1992. In our research, we infer the properties of the stratospheric aerosols from these spectra. The instrument employs two different detectors, a HgCdTe photoconductor for 650-1850 cm(-1) and an InSb photodiode for 1850-5650 cm(-1), to simultaneously record the solar intensity throughout the mid-infrared. These spectra have been used to retrieve the concentrations of a large number of gases, including chlorofluorocarbons, NOy species, O3, and ozone-depleting gases. We demonstrate how the residual continua spectra, obtained after accounting for the absorbing gases, can be used to obtain information about the stratospheric aerosols. Infrared extinction spectra are calculated for a range of modeled aerosol size distributions and compositions with Mie theory and fitted to the measured residual spectra. By varying the size distribution parameters and sulfate weight percent, we obtain the microphysical properties of the aerosols that best fit the observations. The effective radius of the aerosols is found to be between 0.4 and 0.6 microm, consistent with that derived from a large number of instruments in this post-Pinatubo period. We demonstrate how different parts of the spectral range can be used to constrain the range of possible values of this size parameter and show how the broad spectral bandpass of the MkIV instrument presents a great advantage for retrieval ofboth aerosol size a nd composition over instruments with a more limited spectral range. The aerosol composition that provides the best fit to the measured spectra is a 70-75% sulfuric acid solution, in good agreement with that obtained from thermodynamic considerations.

Journal Article↗
PubMed2006

Suggestion for qualitative lidar identification of different types of aerosol using the two-wavelength rotational Raman and elastic lidar.

Aerosols are important parameters in the meteorological and environmental fields, and remote aerosol identification is extremely desirable. We have proposed and designed a two-wavelength (355 and 532 nm) rotational Raman and elastic lidar that can measure the wavelength dependence of the aerosol backscattering coefficient without any assumptions about the Angström coefficient or the overlapping function from low (100 m) to high (10 km) altitude, depending on the weather conditions. We have measured the differences in the backscattering ratios (BRs) among a cloud, aerosol in the boundary layer, and Asian dust. The ratio of the aerosol backscattering coefficients between two wavelengths is a fingerprint of an aerosol, which is similar to the Angström coefficient. The BR value for a typical aerosol ranged from 0.56 to 0.4 in the boundary layer and from 0.5 to 0.1 for Asian dust. The BR value of water droplet was not unique but was spread over a wide range because of its size distributions.

Journal Article↗
PubMed2000

Concentrations of gentamicin in serum and bronchial lavage fluid after intravenous and aerosol administration of gentamicin to horses.

OBJECTIVE: To compare concentrations of gentamicin in serum and bronchial lavage fluid after IV and aerosol administration of gentamicin to horses. ANIMALS: 9 healthy adult horses. PROCEDURE: Gentamicin was administered by aerosolization (20 ml of gentamicin solution [50 mg/ml]) and IV injection (6.6 mg of gentamicin/kg of body weight) to each horse, with a minimum of 2 weeks between treatments. Samples of pulmonary epithelial lining fluid were collected by small volume (30 ml) bronchial lavage 0.5, 4, 8, and 24 hours after gentamicin administration. Serum samples were obtained at the same times. All samples were analyzed for gentamicin concentration, and cytologic examinations were performed on aliquots of bronchial lavage fluid collected at 0.5, 8, and 24 hours. RESULTS: Gentamicin concentrations in bronchial lavage fluid were significantly greater 0.5, 4, and 8 hours after aerosol administration, whereas serum concentrations were significantly less at all times after aerosol administration, compared with IV administration. Neutrophil counts in bronchial lavage fluid increased from 0.5 to 24 hours, regardless of route of gentamicin administration. CONCLUSIONS AND CLINICAL RELEVANCE: Aerosol administration of gentamicin to healthy horses resulted in gentamicin concentrations in bronchial fluid that were significantly greater than those obtained after IV administration. A mild inflammatory cell response was associated with aerosol delivery of gentamicin and repeated bronchial lavage. Aerosol administration of gentamicin may have clinical use in the treatment of bacterial bronchopneumonia in horses.

Administration, Inhalation↗
PubMed1994

Evaluation of a prototype expiratory-phase aerosol controller during simulated pediatric volume-controlled ventilation.

BACKGROUND: Some methods of administering aerosolized medications during volume-controlled ventilation require adjustment of ventilator settings to avoid inadvertent increases in tidal volume (VT). Our bench evaluation of an expiratory-phase aerosol controller (EXPAC) sought to determine the differences (1) in aerosol delivery between continuous and EXPAC nebulization in pediatric and neonatal ventilator circuits and (2) in delivered VT with a 30-cm vs a 213-cm nebulizer supply line. DESCRIPTION OF DEVICE: An electrically powered EXPAC linked to the VIP Bird ventilator by a fiberoptic cable and driven by flow from an integral blender was developed to our performance specifications. EVALUATION METHODS: In Phase 1, VT was measured at the patient connection under 3 conditions: (1) no nebulizer in-line, (2) a dry in-line nebulizer driven by EXPAC with a 30-cm supply line, and (3) Condition 2 with a 213-cm supply line. In Phase 2, we measured the aerosol delivered to a filter placed between the patient connector and the test lung. Aerosol delivery = filter wet weight-filter dry weight. RESULTS: (1) When EXPAC was operated according to manufacturer's recommendations, no significant differences were found between VTS measured with EXPAC plus the 30-cm line and with no nebulizer in-line. VT increased significantly (p = 0.0001, 1-way ANOVA) in both circuits with the 213-cm supply line. (2) Mean (SD) aerosol delivery at the patient connection of the pediatric circuit was 1.5 (0.002)% with EXPAC and 1.7 (0.003)% with continuous nebulization (p = 0.23, t test) and of the neonatal circuit 1.6 (0.002)% with EXPAC and 1.5 (0.002)% with continuous nebulization (p = 0.45, t test). CONCLUSIONS: EXPAC eliminated need for adjustment of ventilator settings and according to our data was as effective as continuous nebulization for delivering aerosol to the patient connection.

Administration, Inhalation↗
PubMed2003

Description and evaluation of a delivery system for aerosolized prostacyclin.

INTRODUCTION: Inhaled vasodilators such as nitric oxide and aerosolized prostacyclin (PGI(2)) are used to treat severe hypoxemia in acute respiratory distress syndrome. Preferential distribution of nitric oxide and PGI(2) to ventilated areas of the lung causes selective pulmonary vasodilation, improved ventilation/perfusion matching, and decreased hypoxemia. Because of the technical limitations of previously described methods, we developed a PGI(2) delivery technique that allows the aerosolized drug dose to be easily calculated, set, and adjusted. METHODS: A 50 mL solution of PGI(2) (3.0x10(4) ng/mL) and a 500 mL normal saline solution were infused by a dual-channel volumetric infusion pump into a MiniHEART jet nebulizer that has a manufacturer-specified output of 8 mL/h at a set flow of 2 L/min. By adjusting the pump infusion rate to achieve a total output of 8 mL/h, the PGI(2) concentration was altered to deliver a calculated aerosolized dose of 10-50 ng/kg/min. The effectiveness of the delivery system was retrospectively evaluated by way of the responses of 11 severely hypoxemic acute respiratory distress syndrome patients who received PGI(2) via the system we describe. The MiniHEART nebulizer output, particle size, and dose delivery were evaluated in a laboratory bench study, using a set flow of 2 L/min. RESULTS: Aerosolized PGI(2) therapy (mean dose 28 +/- 17 ng/kg/min, range 10-50 ng/kg/min) significantly increased the ratio of P(aO)(2) to fraction of inspired oxygen (P(aO)(2)/F(IO)(2)) (60 +/- 11 mm Hg vs 80 +/- 17 mm Hg, p = 0.003) and arterial oxygen saturation measured via pulse oximetry (86 +/- 8% vs 94 +/- 3%, p = 0.005) (differences evaluated with the Wilcoxon signed rank test). There was no difference in positive end-expiratory pressure, mean airway pressure, or F(IO)(2), before and after aerosolized PGI(2) (p > 0.05). Nebulizer output was 6.8 +/- 0.9 mL/h, range 6.0-7.8 mL/h. The inhaled aerosol particles had a mass median diameter of 3.1 micro m. Emitted dose was 67 +/- 13% (range 57-81%) of the calculated dose. CONCLUSION: Our system is effective in delivering aerosolized PGI(2) to the alveolar-capillary interface, as indicated by significant oxygenation improvements soon after therapy commenced. The performance of the MiniHEART nebulizer varies from the manufacturer's specifications, which may alter the delivered dose.

Administration, Inhalation↗
PubMed1997

Tetrafluoroethane (HFC 134A) propellant-driven aerosols of proteins.

PURPOSE: Develop metered-dose propellant-driven aerosols of proteins using tetrafluoroethane (HFC 134A) as propellant. METHODS: Proteins were lyophilized with the propellant-soluble surfactants Triton X-100, Triton X-405, Laureth-9, Brij-30, Nonidet-40, and diethylene glycol monoethylether and then charged with propellants. RESULTS: Small particle aerosols of the experimental protein bovine gamma globulin were produced. The fraction of aerosolized respirable-sized protein particles (< 4-5 microns) increased after dispersion of particles in propellant with agitation by shaking. Scanning electron microscopy of respirable-sized protein aerosols demonstrated bead-like particles in grape-like clusters. Vigorous shaking of propellant-suspended particles for 2 minutes or more reduced the size of clusters and reduced the diameters of the protein-containing subparticles that constituted the clusters. A 50:50 ratio of HFC 134A and dimethylether (DME) propellants improved the respirability of protein aerosols compared to HFC 134A as the sole propellant. Protein/surfactant particles first dispersed in DME and then diluted in HFC 134A propellant most efficiently produced respirable-sized, propellant-driven, protein aerosols.

Aerosol Propellants↗
PubMed2000

Physicochemical factors governing the performance of nedocromil sodium as a dry powder aerosol.

Previous investigations have found that the in vitro aerosol performance of nedocromil sodium is poor. A study has been undertaken to gain a better understanding of the physicochemical properties of the drug particles together with the factors governing the aerosol performance of inhalation systems containing this drug. Material previously passed through a hammer mill only and particles subsequently passed through a micronizer were characterized, and the information gathered was correlated with the in vitro aerosol performance of the pure drug systems. Optimization of particle sizing procedures revealed that both sets of materials were ultrafine powders with a volume median diameter of approximately 1 microm. It is concluded that the processing stages, employed in the manufacture of these batches of fine particle nedocromil sodium trihydrate, may not in fact be primary particle size reduction stages but instead deaggregation stages and that these govern the aerosol performance. The in vitro aerosol performance of samples of the "micronized" nedocromil sodium stored over a range of relative humidities (RHs) was characterized. Storage RHs in the range 12-76% (where nedocromil sodium is stable as the trihydrate) did not have a dramatic effect on the in vitro aerosol performance of the drug. However, conversion to the heptahemihydrate (following storage of the drug at 86% RH) significantly decreased the deaggregation performance in an in vitro model.

Administration, Inhalation↗
PubMed2000

Bacterial aerosols in the dental clinic: effect of time, position and type of treatment.

OBJECTIVES: The objectives of this study were to investigate changes in the concentration of total bacterial aerosols before, during, and after the working period at different positions within the same multichair dental clinics. Also to investigate the contribution to total bacterial aerosols, if any, of the aerosols generated from different types of dental procedures, as well as the environment. METHODS: Air sampling using a Slit-to-Agar air sampler at three positions in a multichair dental clinic, performed three times per day over a three week period before work, during work and after work. The second part of the study, in another multichair dental clinic, was performed before working and during three types of dental procedures. RESULTS: The concentration of total bacterial aerosols and Bacillus sp. in air which circulated in the dental clinic was lower at the end of the day than at the beginning. There was no significant change in the concentration of total bacterial aerosols in different positions in the dental clinic or after the three types of dental treatments. The concentration of Bacillus sp. in air not mainly generated during dental procedures and which may come from an environmental source, was reduced. CONCLUSIONS: This study suggests that the proportions of different types of bacteria in air may change before, during and after dental treatment. Preventive measures may need to be instituted to reduce build up of bacterial aerosols in the dental clinic during non-working periods.

Aerosols↗
PubMed2004

Assessment of regional lung function impairment in airway obstruction and pulmonary embolic dogs with combined noncontrast electrocardiogram-gated perfusion and gadolinium diethylenetriaminepentaacetic acid aerosol magnetic resonance images.

PURPOSE: To define regional function impairment in airway obstruction (AO) and pulmonary embolic (PE) dogs with a combination study of noncontrast electrocardiogram (ECG)-gated perfusion and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) aerosol magnetic resonance (MR) images. METHODS: After acquisition of multiphase fast-spin-echo (FSE) MR images during cardiac cycles in 14 AO dogs and 19 PE dogs, ECG-gated perfusion-weighted (PW) images were obtained by subtraction between two-phase images of the minimum lung signal intensity (SI) during systole and maximum SI during diastole. Each dog subsequently inhaled Gd-DTPA aerosol for 20 minutes, and subtracted Gd-DTPA aerosol images were obtained from precontrast and maximally enhanced images. ECG-gated PW images were compared with intravenous Gd-DTPA-enhanced pulmonary arterial perfusion phase (PAPP) images. RESULTS: ECG-gated PW images were consistent with Gd-DTPA-enhanced PAPP images in all dogs, with significant correlations in the affected-to-unaffected lung perfusion ratios (P < 0.005). Gd-DTPA aerosol images showed sufficient and uniform enhancement in the unaffected lungs. In all the AO areas, these combined images showed the matched perfusion and aerosol deposition defects. These images showed perfusion defects without aerosol deposition defects in the relatively small embolized areas, but showed the matched defects in the widely embolized areas probably due to hypoxic bronchial constriction. CONCLUSION: The combination MR studies may be acceptable for noninvasively defining regionally impaired lung function in AO and PE.

Administration, Inhalation↗
PubMed2005

Electrostatic charge characteristics of aerosols produced from metered dose inhalers.

The electrostatic charge properties of aerosols produced by commercial metered dose inhalers (MDIs), including Ventolin, QVAR, Flixotide, Intal Forte, and Tilade were studied using a modified 13-stage electrical low pressure impactor (ELPI) with aerodynamic diameter cutoff ranging from 0.028 to 10.07 microm. All the stages are electrically insulated from each other with the last 12 stages connected individually to electrometers with sensitivity at femtoampere levels. Aerosol particles deposited on the impactor stages according to their aerodynamic diameters and their charges were measured by the electrometers. The deposited drug mass was assayed chemically using HPLC. The results show that particles of bipolar charge distribution were produced reproducibly from Intal Forte, Tilade, and Flixotide. In contrast, those from Ventolin and QVAR displayed charge variation, depending on the time lapse between actuations. This suggests that charge relaxation may influence the charging of these two MDIs. Mass distributions were reproducible for all MDIs except for Ventolin, the first puff from which was always the highest in dose. The different charge characteristics of the MDIs could be attributed to differences in the drug and formulation as well as valve materials. In general, submicron particles showed a larger variation in the charge-to-mass ratio (q/m). This indicated charge contribution by propellant/excipients (which produce submicron particles) rather than the drug itself. The calculated number of elementary charges per drug particle of size <or= 6.06 microm ranged from zero to several ten thousands. The charge level is sufficiently high to have a potential effect on the deposition of the inhaled particles in the respiratory tract. In conclusion, the ELPI provided more detailed charge information about the MDI aerosol particles. Different aerosol charge profiles were shown by commercial MDIs, and the results can be explained by variation in the drug, formulation and the MDI materials. The results may have practical significance on lung deposition of MDI aerosols and regulatory aspects of generic aerosol products.

Aerosols↗
PubMed1987

Spinning-disk generation and drying of monodisperse solid aerosols with output concentrations sufficient for single-breath inhalation studies.

The air-driven spinning-disk aerosol generator was modified to allow the production of monodisperse dry spherical aerosols of disodium fluorescein (as model solute) in high output concentrations. Output concentrations were determined by filtration. Optical and aerodynamic size distributions were determined microscopically (after electrostatic precipitation) and by cascade impaction. The generator housing allowed the entrainment of 25-microns primary aqueous solution droplets in a 10-L X min-1 downward flow of dry, filtered air. Internal equipment surfaces were machined flush and polished to minimize aerosol losses. Primary droplets were dried within a stainless steel pipe encased in a tube furnace. Water vapor was removed by diffusion drying. Disk-driven air, satellite droplets, and additional dilution air were vented to waste without using a vacuum. Generator yields were increased by reducing the size of the satellite droplet extraction gap. Aerosols were generated reproducibly by delivering aqueous solutions at a rate of 0.2 mL X min-1 to the center of the disk and spinning at 1000 rps. Dry aerosols, with mass median aerodynamic diameters of 2, 4.9, and 9 microns, were produced in concentrations of 0.89, 5.48, and 54.6 micrograms X L-1 from aqueous solutions containing 0.0374, 0.584, and 3.4% solute by weight. Geometric standard deviations were less than 1.2 in all cases. Concentrations are several times higher than others in the literature and are suitable for single-breath inhalation studies of therapeutic aerosol deposition and effect.

Aerosols↗
PubMedDate not supplied

Vasodilatory effect of aerosol histamine during pulmonary vasoconstriction in unanesthetized sheep.

The effects of aerosol histamine on pulmonary vascular resistance during pulmonary vasoconstriction were studied in 12 unanesthetized sheep. Sheep were chronically instrumental with Silastic catheters in the pulmonary artery and left atrium, thermodilution Swan-Ganz catheter in the main pulmonary artery for measurement of cardiac output, and tracheostomy for delivery of hypoxic gas and/or aerosol histamine. Seven minutes of isocapnic hypoxia (FIO2 = 0.12) caused pulmonary artery pressure (PPA) to increase from 17.2 +/- 0.4 to 27.0 +/- 1.0 cm H2O (mean +/- SEM, P less than 0.05) and pulmonary vascular resistance (PVR) to increase from 3.94 +/- 0.33 to 4.71 +/- 0.38 cm H2O x L-1 x min (P less than 0.05). When sheep breathed a combination of aerosol histamine (5 mg/ml) and 12% O2, PPA rose only 21.3 +/- 1.11 cm H2O and PVR decreased to 3.51 +/- 0.31 cm H2O x L-1 x min. This was a significantly (P less than 0.05) smaller response compared to hypoxia alone. Aerosol histamine alone had to significant effect on PPA or PVR. Meclofenamate did not restore the histamine-induced loss of hypoxic vasoconstriction. Aerosol histamine significantly blunted the pulmonary vasoconstriction caused by intravenous serotonin (8 micrograms/kg/min) and intravenous prostaglandin H2-analog (0.74 microgram/kg/min). It was concluded that in the awake sheep aerosol histamine acted as a pulmonary vasodilator only in the presence of pulmonary vasoconstriction.

Aerosols↗
PubMed1993

Alteration of pulmonary macrophage intracellular pH regulation by sulfuric acid aerosol exposures.

In vivo exposure to sulfuric acid aerosols produces profound effects on pulmonary macrophage (PM phi) phagocytic function and cytokine release and perturbs intracellular pH (pHi) homeostasis. Because pHi influences a multitude of cellular processes, we sought to investigate the mechanism by which acid aerosol exposure affects its regulation. Guinea pigs underwent a single or 5 repeated 3-hr exposures to sulfuric acid aerosol (969 and 974 micrograms/m3 for single and repeated exposures, respectively). PM phi harvested immediately after exposure were incubated in HCO3-free media and their pHi recovery from an intracellular acid load was examined. The overall pHi recovery was depressed after single and multiple exposures to sulfuric acid aerosol. delta pHi (the difference between initial pHi and the one measured at 150 sec) decreased by 15.6 and 23.3% (p < 0.05) for single and repeated exposures, respectively. Initial dpHi/dt (maximum pHi recovery rate) after cytoplasmic acidification diminished by 20.3 and 32.2%, which were not statistically significant (p = 0.08 for repeated exposure). To determine whether the activity of the H(+)-ATPase pump the Na(+)-H+ exchanger was specifically altered by the acid exposures, PM phi were first incubated in Na+ and HCO3-free media with NBD-Cl (7-chloro-4-nitrobenz-2-oxa-1,3-diazol, blocking H(+)-ATPase and leaving only the Na(+)-H+ exchanger in effect) and then challenged with 30 mM NaCl. The pHi recovery of PM phi after Na challenge was significantly reduced in acid aerosol exposed guinea pigs (p < 0.05) compared to controls (for delta pHi, 18.2% lower in single exposure and 22.7% in multiple exposure groups; for initial dpHi/dt, 26.9% lower in single exposure and 22.4% in multiple exposure groups). In contrast, the H(+)-ATPase pump was inconsistently affected as indicated by delta pHi and initial dpHi/dt measured in the presence of MIA (amiloride-5-N-methylisobutyl, inhibiting the Na(+)-H+ exchanger and leaving only the H(+)-ATPase pump in effect). These results suggest that in vivo exposure to sulfuric acid aerosols induces alterations in pHi regulation in guinea pig PM phi attributable to changes in Na(+)-H+ exchanger activity.

Administration, Inhalation↗
PubMed1993

Chronic pentamidine aerosol prophylaxis does not induce QT prolongation.

Intravenous administration of pentamidine is known to cause long-QT syndrome (Torsade de pointes tachycardias and large QT prolongation) in rare cases and to cause small QT prolongation regularly. A similar pattern is seen with other drugs known to cause a long-QT syndrome. Pentamidine aerosol prophylaxis is commonly used to prevent Pneumocystis carinii pneumonia in HIV-infected persons. The goal of this study was to clarify whether pentamidine aerosol prophylaxis induces QT prolongation. We examined 100 patients receiving pentamidine aerosol prophylaxis at a rather high dose (300 mg biweekly) for at least 1 month (range 1-24) by determining the QT interval corrected for heart rate (QTc), blind for treatment. In a cross-sectional study, QTc was not different in 50 HIV-infected patients with chronic pentamidine aerosol prophylaxis (413 ms), 50 similar HIV-infected patients without pentamidine (407 ms), and 50 similar patients without HIV-infection and without pentamidine (407 ms). In a longitudinal study in another 50 HIV-infected patients, QTc was the same before (414 ms) and on long-term (median 9-month) pentamidine aerosol prophylaxis (414 ms). In contrast to the case with intravenous pentamidine, we found no QT prolongation and thereby no risk of long-QT syndrome with pentamidine aerosol prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed1982

Role of vagus nerves and inhalative aerosols of acetylcholine and histamine on dynamic pulmonary elastance in anesthetized spontaneously breathing and artificially ventilated dog.

The role of the vagus nerves on resting respiratory resistance (R1) and dynamic lung elastance (Edyn) and the mechanism of action of inhaled aerosol of histamine (Hist) and acetylcholine (ACH) were studied in anesthetized spontaneously breathing and artificially ventilated dogs. Observations were also extended to study the effect of electrical stimuli to cut ends of both vagi alone and during inhalation of aerosols. Bilateral cervical vagal blockade by local application of novocaine solution (2.5%) or bilateral vagotomy reduced resting R1 and Edyn and prevented increase of these parameters following inhalation of aerosols of Hist or ACH in spontaneously breathing dogs. However, the similar vagal blockade or vagotomy in artificially ventilated animals showed neither an influence on resting R1 and Edyn nor could it prevent their increase following the exposure to aerosol of Hist or ACH. Electrical stimuli to the peripheral cut ends of vagi induced slight increase in R1 and Edyn, but the effect on heart rate and systemic blood pressure was very strong. The combined effects of aerosol of Hist or ACH and electrical stimuli were additive. It is concluded that inhalation of aerosol of Hist or ACH produced two kinds of effects on respiration: (1) Increased respiratory rates with reduced tidal volume and with bronchoconstriction which were vagus-dependent (spontaneous breathing model), and (2) bronchoconstriction which was a direct response of smooth muscle without involving a reflex (artificial ventilation model).

Acetylcholine↗
PubMed2006

Aerosol gene delivery to the murine lung is mouse strain dependent.

The cationic polymer polyethylenimine (PEI) has been previously demonstrated to efficiently deliver genes to the lungs of mice in vivo via nebulization. Although within these studies various mouse strains were used in individual experiments, no direct comparison of gene delivery to different mouse strains via aerosol application has been published to date. With respect to the widespread use of mice as animal models of inherited and acquired diseases, such data could be of relevance to select the most appropriate mouse genetic background for preclinical mouse models. We investigated PEI-based aerosol gene delivery in two commonly used mouse strains, BALB/c and NMRI, and mixed 129/Sv x C57BL/6 mice. Gene expression in BALB/c mice was significantly 3.2- and 3.8-fold higher than in NMRI and 129/Sv x C57BL/6 mice, respectively. Lung deposition rates of radioactively labeled plasmid DNA (I(123)) complexed with PEI were not significantly different between each of the mouse strains. The kinetics of pDNA clearance from the lungs of BALB/c mice was slightly faster than from NMRI mice. Whereas gene expression increased until day 3 after treatment, the levels of pDNA decreased over the same period of time. Repeated aerosol application in a 3-day time interval could maintain gene expression at high levels compared with a single application. Furthermore, PEI-pDNA aerosol application led to reproducible gene expression in independent experiments. These data suggest that the genetic background of mice could be important for nonviral aerosol gene delivery which should be considered in transgenic animal mouse models of inherited and acquired diseases for aerosol gene delivery studies.

Administration, Inhalation↗