Inhalation volume/flow

The tubes or sniffing ports in use have various designs. The main condition is that the panelist should be supplied with the minimum breathing volume flow and that he should not inhale air from outside the sniffing port. In present practice,.there are volume flows between 16 and 170. 1. mhr1 (0.96-10 m3. IT1). 

Frank in dogs. The most likely explanation is that the model does not account for chemical reactions of ozone in the mucus and epithelial tissue. Another problem is that the nose is believed to behave more like a scrubbing tower with fresh liquid at each level, inasmuch as the blood supply is not continuous for the entire length of the nose, as assumed in the model. Neglecting the surface area, volume, flow, and thickness of the mucus layer in the nose will probably also give erroneous results for soluble gases with a small diffusion coefficient in mucus and for singlebreath inhalations of a low concentration of any gas. 

A number of pharmaceutical companies are developing INH dehvery systems using both liquid and dry-powder insulin formulations [34,35]. Table 4 briefly indicates those arrived at in phase HI studies. A few companies have developed systems based on hquid formulations, which utilize relatively complex pressurized metred-dose devices or nebuUzation systems to generate appropriately sized aerosolized doses, hi the AERx system inhalation flow rate, inhaled volume and duration are patient-controlled... 

Flow rate Inhaled volume Breath hold... 

Pavia et al. randomly assigned inhalation volumes ranging from 0.11 to 0.88 L to 44 patients with airways obstruction and measured the alveolar deposition of radiolabeled polystyrene particles (5 + 0.7 pm) generated from an MDI. The patient s FEVj and inspiratory flow rate were also measured. A multiple regression analysis of the alveolar deposition, inhalation volume, FEV, and inspiratory flow rate revealed that for every liter increase in inhalation volume and for every liter increase in FEVj, the alveolar deposition rose by 40 and 11%, respectively. In contrast, alveolar deposition decreased by 0.75% for every 1 L/min inaease in inspiratory flow rate (19). 

Metered volumes of hquid are similar to those used with pMDls, i.e., around a 100 pL. Volume flow rates through a single nozzle are not sufficient to deliver such liquid volumes during a single breath, and instead the metered volume flows in parallel through about 1,000 identical nozzles to generate the inhaled spray cloud. 

The volume of air per unit time through an inhaler during inspiration is the inspiratory flow rate, which is expressed in L/min. Generally, the flow rate through an inhaler quite rapidly reaches a maximum value (peak inspiratory flow, PIF) followed by a slower decrease to zero flow. As a general rule, the average flow rate equals approximately 70 % of PIF. From the average flow rate and the total inhalation time the inhaled volume (V) can be computed. The flow rate influences the particle size distribution in the aerosol and the deposition pattern in the respiratory tract. 

Oxygen is suppHed quite routinely to patients suffering impaired respiratory function as weU as in other situations where oxygen is deemed to be useflil. The pure oxygen, with humidification, is deHvered via a simple double tube (cannula) to a point just inside the nostrils where the 99.5% gas blends with the room air (21% O2), and is inhaled. The concentration of oxygen that reaches the lungs thus depends on the rate and volume of air inhaled and on the exit flow of oxygen from the cannula, usually one to six L/min. 

Forced vital capacity (FVC) quantifies the maximum air volume expired following a maximal inspiration and is one of the basic measures of analyzing flow changes such as reduced airway patency observed in asthma. To measure FVC, an individual inhales maximally and then exhales as rapidly and completely as possible. FVC primarily reflects the elastic properties of the respiratory tract. The gas volume forcibly expired within a given time interval, FEV (where t is typically one second, FEVj q)... 

FEV, forced expiratory volume in 1 second PEF, peak expiratory flow MDI, metered-dose inhaler DPI, dry powder inhaler. 

Spirometry Measurement of inhaled and exhaled volumes and flow rates of gas from the lungs. Pulmonary function tests obtained from spirometry are used to aid in the diagnosis of obstructive and restrictive airway diseases. 

Six male Wistar rats inhaled HCN at 55 ppm for 30 min (Bhattacharya et al. 1984). HCN was generated by reaction of KCN with sulfuric acid and circulated through the chamber at the rate of 1 L/min. The rats were fitted with a lung mechanics analyzer (Buxco Electronic Inc.), and changes in air flow, transthoracic pressure, tidal volume, compliance, resistance, respiratory rate, and minute volume were determined every 10 min. Animals were sacrificed immediately following the exposure, and lungs were excised and analyzed for phospholipids (surfactant). 

In general, slow, deep inhalation followed by a period of breath holding increases the deposition of aerosols in the peripheral parts of the lungs, whereas rapid inhalation increases the deposition in the oropharynx and in the large central airways. Thus, the frequency of respiration (the flow velocity) and the depth of breath (tidal volume) influence the pattern of pulmonary penetration and deposition of inhaled aerosols. Therefore, an aerosol of ideal size will penetrate deeply into the respiratory tract and the lungs only when the aerosols are inhaled in the correct manner (Sackner, 1978 and Sackner et al., 1975). 

The respiratory effects of cyanide include dyspnea, asphyxia, and a decrease in respiratory rate (Blanc et al. 1985 Matijak-Schaper and Alarie 1982 McNemey and Schrenk 1960). A recent study (Bhattacharya et al. 1994) demonstrated increased air flow, transthoracic pressure, and tidal volume accompanied by a significant decrease in pulmonary phospholipids following inhalation of hydrogen cyanide in rats. This study also showed that hydrogen cyanide exhibited a direct effect on pulmonary cells in rats. 

Many different techniques are available for flow measurement and for recording of respiratory functions or flow parameters in particular (e.g. [115,116]). However, not all methods are appropriate for measurement of inhalation flows, either because they have low frequency responses or they influence the shape of the inspiratory flow curve by a large volume or by the inertia of the measuring instrument (e.g. rotameters). They may also interfere with the aerosol cloud from the inhalation device during drug deposition studies. 

The concentration of an inhaled anesthetic in a mixture of gases is proportional to its partial pressure (or tension). These terms are often used interchangeably in discussing the various transfer processes involving anesthetic gases within the body. Achievement of a brain concentration of an inhaled anesthetic necessary to provide an adequate depth of anesthesia requires transfer of the anesthetic from the alveolar air to the blood and from the blood to the brain. The rate at which a therapeutic concentration of the anesthetic is achieved in the brain depends primarily on the solubility properties of the anesthetic, its concentration in the inspired air, the volume of pulmonary ventilation, the pulmonary blood flow, and the partial pressure gradient between arterial and mixed venous blood anesthetic concentrations. 

Inhaled anesthetics decrease the metabolic rate of the brain. Nevertheless, the more soluble volatile agents increase cerebral blood flow because they decrease cerebral vascular resistance. The increase in cerebral blood flow is clinically undesirable in patients who have increased intracranial pressure because of a brain tumor or head injury. Volatile anesthetic-induced increases in cerebral blood flow increase cerebral blood volume and further increase intracranial pressure. 

An increase in pulmonary blood flow (increased cardiac output) slows the rate of rise in arterial tension, particularly for those anesthetics with moderate to high blood solubility. This is because increased pulmonary blood flow exposes a larger volume of blood to the anesthetic thus, blood "capacity" increases and the anesthetic tension rises slowly. A decrease in pulmonary blood flow has the opposite effect and increases the rate of rise of arterial tension of inhaled anesthetics. In a patient with circulatory shock, the combined effects of decreased cardiac output (resulting in decreased pulmonary flow) and increased ventilation will accelerate the induction of anesthesia with halothane and isoflurane. This is not likely to occur with nitrous oxide, desflurane, or sevoflurane because of their low blood solubility. 

The animals should be tested with inhalation equipment designed to sustain a dynamic air flow of 12 to 15 air changes per hour, and to ensure an adequate oxygen content of 19% and an evenly distributed atmosphere. Whenever a chamber is used, its design should minimize crowding of test animals and maximize their exposure to the chemical. As a general rule, to ensure stability of the chamber atmosphere, the total volume of the test animals should not exceed 5% of the test chamber volume. Alternatively, oronasal, head only, or whole-body individual exposure chambers may be used. 

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