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Biomedical subjects

N Gavriely

Publications and source records attributed to N Gavriely.

At least 55 records · Page 3Linked to original sources

Flutter in collapsible tubes: a theoretical model of wheezes.

A mathematical analysis of flow through a flexible channel is examined as a model of flow-induced flutter oscillations that pertain to the production of wheezing breath sounds. The model provides predictions for the critical fluid speed that will initiate flutter waves of the wall, as well as their frequency and wavelength. The mathematical results are separated into linear theory (small oscillations) and nonlinear theory (larger oscillations). Linear theory determines the onset of the flutter, whereas nonlinear theory determines the relationships between the fluid speed and both the wave amplitudes and frequencies. The linear theory predictions correlate well with data taken at the onset of flutter and flow limitation during experiments of airflow in thick-walled collapsible tubes. The nonlinear theory predictions correlate well with data taken as these flows are forced to higher velocities while keeping the flow rate constant. Particular ranges of the parameters are selected to investigate and discuss the applications to airway flows. According to this theory, the mechanism of generation of wheezes is based in the interactions of fluid forces and friction and wall elastic-restoring forces and damping. In particular, a phase delay between the fluid pressure and wall motion is necessary. The wave speed theory of flow limitation is discussed with respect to the specific data and the flutter model.

Humans↗

Effect of salicylate on upper airway dilating muscles in anesthetized dogs.

It is well documented that salicylate given in large doses stimulates ventilation. As increased ventilatory drive is often associated with augmented upper airway dilating muscle activity, we evaluated in anesthetized dogs the effect of salicylate on the electrical activity of three upper airway muscles, the alae nasi, the genioglossus, and the posterior cricoarytenoid. The electromyograms of these muscles were compared with those of the diaphragm before and at 15-min intervals after intravenous salicylate administration (250 mg/kg). Salicylate induced a gradual increase in ventilation and in the electrical activity of all muscles examined (p less than 0.001). Compared to baseline activity, salicylate increased the electrical activity of the genioglossus more than that of the diaphragm (p less than 0.01). The increase in upper airway muscle activity was observed also in vagotomized dogs, and was not accounted for by changes in arterial blood gases or pH. Increases in upper airway muscle electrical activity were associated with a significant decrease in upper airway resistance to airflow (mean reduction of 62 +/- 7% SE, p less than 0.01). The preferential increase in genioglossus electrical activity and the decrease in upper airway resistance observed in this study with salicylate suggest that salicylate, and possibly other pharmacologic agents that stimulate ventilation, may improve upper airway patency.

Airway Resistance↗

Gas conductance during high-frequency oscillatory ventilation in large animals.

Three sheep, a foal, a pony, and a calf were anesthetized and ventilated for short periods, using a high-frequency oscillatory ventilator. The efficiency of CO2 elimination was characterized at various oscillatory frequencies (50 to 30 Hz) and various tidal volumes, although the tidal volume used was always less than the measured dead space of the animal. In general, increasing either the oscillatory frequency or tidal volume increased CO2 elimination, but increasing the tidal volume had more effect. The relationship between these 3 variables was best described by a power law equation. Ventilatory frequencies and tidal volumes required to maintain eucapnia in the species studied were extrapolated from the results and, when technically possible, the potential of the technique to maintain eucapnia was tested in extended runs. The animals were supported successfully over this period, with normal blood gas tensions and no detrimental effects to heart rate and rhythm or arterial blood pressure.

Anesthesia↗

Effect of salicylate on upper airway stability and pressure flow: relationship in anesthetized dogs.

Previous studies have shown that upper airway muscle activity is augmented in response to increased respiratory drive, thereby improving upper airway patency. In the present study we evaluated the effect of salicylate, a well-known respiratory stimulant, on upper airway stability and pressure-flow relationship. Multiple levels of airflow were used to assess pressure-flow relationship in the isolated airways of anesthetized dogs and to calculate the coefficients of Rohrer's equation P = K1V + K2V2. In addition, we measured the negative intraluminal pressure needed to collapse the upper airway. These measurements were repeated after intravenous administration of sodium salicylate, 250 mg/kg. Salicylate-induced hyperventilation was associated with increased alae nasi electrical activity. Resistance to airflow and K2 decreased significantly (p less than 0.01), suggesting dilation of the upper airway lumen. The intraluminal pressure under which upper airway collapse occurred became more negative in all dogs (from -5.0 +/- 0.8 to -8.5 +/- 1.3 cm H2O, p less than 0.01), indicating improved stability of the upper airway walls. These findings suggest that salicylate, and presumably other pharmacologic agents that stimulate ventilation, can improve both upper airway patency and upper airway stability.

Airway Resistance↗

The effect of gravity on the response of ventilation to abrupt change in FICO2.

Recently, Arieli and Farhi (1987) formulated a model for a previous suggestion made by their group that an increased ventilation as gravity increases is due to reduced perfusion of the respiratory center which causes an elevation of tissue PCO2. Extending the model to the dynamic response, we predict a slower ventilatory response to CO2 breathing as gravity increases. To test this prediction, ventilatory response to 5% CO2 was studied in 11 seated subjects at +1 and +2 Gz in a human centrifuge. Five of these subjects were studied at +3 Gz as well. In addition, ventilatory response to 5% CO2, using breath-by-breath analysis, was measured in three subjects in supine and upright postures. The ventilatory response (mainly through tidal volume) was faster as gravity increased from +1 to +2 and to +3 Gz, and from supine to the upright position. These findings disagree with the model prediction. Therefore, an alternative explanation is suggested based on the response of CO2 sensitive stretch receptors in the lung. Increased gravity causes increased ventilation, reduction of cardiac output and increased VA/Q mismatch; all enlarge the part of the lung with low CO2 where responsiveness of the CO2 sensitive stretch receptors is large.

Adult↗

Flow limitation and wheezes in a constant flow and volume lung preparation.

To facilitate the study of respiratory wheezes in an animal lung model, an isovolume, constant-flow excised dog lung preparation was developed. Dog lungs were inflated to 26 +/- 4 cmH2O and coated with layers of epoxy glue and polyester compound. A rigid shell 2 mm thick was obtained around the entire pleural surface and the extra-pulmonary airways. The adhesive forces between the pleura and the shell were strong enough to hold the lung distended after the inflation pressure was removed. Holes 2 mm diam were drilled through the shell over one of the lung lobes in an array, 4 cm across. The holes penetrated the pleural surface, so that constant flow could be maintained in the expiratory direction by activating a suction pump connected to the trachea. Downstream suction pressure and flow rate were measured with a mercury manometer and a rotameter, respectively. Sounds were recorded by a small (0.6 cm OD) microphone inserted into the trachea. When suction pressure was increased, flow initially increased to 31 +/- 3 l/min. Further increase of suction pressure caused only very slight additional increase in flow (i.e., flow limitation). During this plateau of flow, a pure tone was generated with acoustic properties similar to respiratory wheezes. Both the flow plateau and the wheezing sounds could be eliminated by freezing the lungs. It is concluded that wheezing sounds were associated with flow limitation in this preparation. It is suggested that the stable acoustic properties obtained by this preparation may become useful in the analysis of mechanisms of wheezing lung sounds generation.

Animals↗

Forced expiratory wheezes are a manifestation of airway flow limitation.

To study the mechanism of generation of respiratory wheezes we examined the relationships between forced expiratory wheezes (FEW) and flow limitation in the lung. Tracheal lung sounds were measured in six healthy subjects during forced expiration through a flow-limiting valve in series with a high-impedance suction pump. Mouth pressure, esophageal pressure, transpulmonary pressure (Ptp), flow (V), and volume were also measured. For any flow rate, V was constant until the subject became flow limited. The onset of flow limitation was documented by a small change in V and a sudden change in Ptp, which was previously found by Olafsson and Hyatt to correspond to the beginning of the flow plateau of the isovolume pressure-flow curve (J. Clin. Invest. 48: 564-573, 1969). FEW started 107 +/- 45 ml (SD) after the onset of flow limitation. Additional 79 +/- 65 ml were exhaled between the onset of FEW to the final sharp drop in V. The frequency spectra of FEW were the same as those of respiratory wheezes found in obstructive airway diseases. Administration of inhaled bronchodilator (isoproterenol) did not eliminate the FEW, nor did it change their relationship to flow limitation. The sequence of events around the onset of FEW, and the tight correlation with the onset of flow limitation correspond well to recent experimental observations on the onset of flutter in collapsible, thick-walled latex tubes.

Adult↗

Effect of tracheal bias flow on gas exchange during high-frequency chest percussion.

High-frequency chest percussion (HFP) with constant fresh gas flow (VBF) at the tracheal carina is a variant of high-frequency ventilation (HFV) previously shown to be effective with extremely low tracheal oscillatory volumes (approximately 0.1 ml/kg). We studied the effects of VBF on gas exchange during HFP. In eight anesthetized and paralyzed dogs we measured arterial and alveolar partial pressures of CO2 (PaCO2) and O2 (PaO2) during total body vibration at a frequency of 30 Hz, amplitude of 0.17 +/- 0.019 cm, and tidal volume of 1.56 +/- 0.58 ml. VBF was incrementally varied from 0.1 to 1.2 l.kg-1.min-1. At low flows (0.1-0.4 l.kg-1.min-1), gas exchange was strongly dependent on flow rate but became essentially flow independent with higher VBF (i.e., hyperbolic pattern). At VBF greater than 0.4 l.kg-1.min-1, hyperventilatory blood gas levels were consistently sustained (i.e., PaCO2 less than 20 Torr, PaO2 greater than 90 Torr). The resistance to CO2 transport of the airways was 1.785 +/- 0.657 l-1.kg.min and was independent of VBF. The alveolar-arterial difference of O2 was also independent of the flow. In four of five additional dogs studied as a control group, where constant flow of O2 was used without oscillations, the pattern of PaCO2 vs. VBF was also hyperbolic but at substantially higher levels of PaCO2. It is concluded that, in the range of VBF used, intraairway gas exchange was limited by the 30-Hz vibration. The fresh gas flow was important only to maintain near atmospheric conditions at the tracheal carina.

Animals↗

Radial and longitudinal compartmental analysis of gas transport during high-frequency ventilation.

A model of gas exchange by low-tidal-volume (VT), high-frequency ventilation (HFV) is presented, based on the physical principles of dispersion. These are the nonuniformity of the velocity profile and the nonreversible mixing of fluid components in a diffusive manner. A numerical method was used to incorporate these principles into a quantitative model. The airways of a symmetrically bifurcating bronchial-tree model were partitioned in the radial direction into two concentric layers representing the kinematic dispersion by nonuniformity of the velocity profile. Mixing between the layers was invoked in proportion to the diffusivity and local dimensions. The effects of frequency (f), VT, shape of the velocity profile, and bronchial-model configuration were tested in the model, with favorable comparison to available experimental data. The model predicts that for a frequency-dependent velocity profile, the rate of tracer exchange is proportional to the square root of f and to the square of VT-V0, where V0 is a constant small volume under which gas exchange was nil. Intracycle asymmetric mixing is predicted to have a stronger effect on gas exchange than asymmetric velocity profile. Gas exchange when turbulent-flow regime is assumed is predicted to be less for the higher VT values than with laminar flow and with mixing by molecular diffusivity. This model was found to be didactic, flexible, and capable of modeling combinations of factors affecting either one of the two fundamental processes of dispersion.

Animals↗

Effect of bias flow rate on gas transport during high-frequency oscillatory ventilation.

Ventilatory support with low tidal volume, high-frequency oscillatory ventilation (HFOV) usually uses a bias flow system to provide fresh gas. Although the bias flow rates (Vbf) used previously have varied widely among experimental configurations, the precise role of the bias flow in HFOV-mediated gas transport has not been defined. We assessed the effect of bias flow rate on gas transport during HFOV by measuring CO2 removal rate (MCO2) in anesthetized, paralyzed dogs, using a wide range of bias flow rates (0.7-28.9 L X min-1). When a fixed tidal volume of 40 ml was applied at HFOV frequencies of 2-12 Hz, MCO2 was proportional to the time-averaged alveolar-bias flow CO2 concentration difference. Thus, when Vbf was reduced below a value which resulted in a substantial increase in bias flow CO2 concentration, MCO2 was reduced. These findings are consistent with a simple framework in which the relative magnitudes of the resistances to gas transport of the airways and of the bias flow (1/Vbf) determine the contribution of the bias flow rate to overall gas transport during HFOV. This relationship may be employed to assess the intra-airway contribution to HFOV-mediated gas transport at any bias flow rate, and may therefore allow comparison of results from experiments utilizing various bias flow rates.

Animals↗

Radiographic visualization of airway wall movement during oscillatory flow in dogs.

It has been suggested that radial movement of the central airway walls during oscillatory flow might contribute to the increased frequency dependence of compliance seen in chronic obstructive pulmonary disease (COPD) (J. Appl. Physiol. 26: 670-677, 1969). Radial airway wall motion has also been invoked to explain the frequency-dependent decreases in the efficiency of gas exchange during low-volume high-frequency ventilation (HFV) in histamine-bronchoconstricted dogs and in patients with respiratory insufficiency. To test the possibility that airway wall motion increases with bronchoconstriction, we measured central airway diameters using cinebronchoradiography in anesthetized tracheostomized dogs during oscillatory HFV [50 and 100 ml tidal volume (VT) at frequencies (f) of 2, 6, and 12 Hz], under control conditions, during electrical stimulation of the vagi, and after exposure to histamine aerosol. Cineradiobronchograms from two dogs were evaluated quantitatively for tracheal diameter and for lengths and diameters of a number of major airways. Under control conditions, the diameter of the airways fluctuated 7-9% of the mean with VT of 50 ml and 9-18% with VT of 100 ml in the range of frequencies studied. Bronchoconstriction produced by aerosolized histamine increased radial airway wall movement to 10-47% with VT of 50 ml, and during vagal stimulation diameters changed 7-20% at VT of 50 ml. After histamine, the central airways displayed large diameter changes during HFV, whereas more peripheral airways were markedly constricted and did not change in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pressure-flow relationships of endotracheal tubes during high-frequency ventilation.

We studied the pressure-flow relationships of various endotracheal tubes (ETT) at frequencies (f) and tidal volumes (VT) in the range used for high-frequency ventilation (HFV) (f: 2-32 Hz, VT: 15-100 ml). Sinusoidal flows were applied to ETT inserted into a rigid bottle or into the tracheae of three anesthetized paralyzed dogs, while pressure fluctuations were measured both proximal and distal to the ETT. The pressure drops in the ETT were nonlinearly related to the peak flow rate and were VT dependent, suggesting that turbulent frictional head loss and convective acceleration were important. The pressure drops measured in vitro were found to be in good agreement with the predictions of a nonlinear oscillatory pressure-flow equation (derived herein), which incorporate the effects of turbulent frictional losses, convective acceleration, inertance, and compliance. The pressure drops measured in situ were 30-50% higher than with the corresponding f-VT combinations in vitro. Possible explanations of these differences are junctional losses at the tip of the ETT or the nonrigid character of the trachea.

Animals↗

Intra-airway gas mixing during high-frequency ventilation.

We examined the intra-airway gas transport mediated by high-frequency oscillations (HFO) in 10 nonintubated healthy volunteers using a method based on comparisons of single-breath N2-washout curves obtained after various durations of breath hold or high-frequency oscillations. With a mathematical analysis based on Fick's law of diffusion we computed the local transport parameter, effective diffusivity, during oscillations of frequency 2-24 Hz and tidal volume 10-120 ml and during breath hold alone. Local effective diffusivity increased with both oscillatory frequency and tidal volume at all levels in the tracheobronchial tree; the enhancing effect of tidal volume on local effective diffusivity was more pronounced than that of frequency so that effective diffusivity was greater with larger tidal volume at fixed frequency-tidal volume product (f . VT). The greatest enhancement of gas mixing within the lung during HFO (over breath hold) was seen in the central airways. In previous studies examining CO2 removal rate during HFO (J. Clin. Invest. 68: 1475, 1981), we found that CO2 output was also greater with larger tidal volume at fixed f . VT, and we attributed this to an end constraint imposed by a fresh gas bias flow. Results of the current study, performed without a bias flow, indicate that bias flow end constraint does not solely account for the observed dependence of CO2 output on frequency and tidal volume.

Adult↗

Measurement and theory of wheezing breath sounds.

We measured the time and frequency domain characteristics of breath sounds in seven asthmatic and three nonasthmatic wheezing patients. The power spectra of the wheezes were evaluated for frequency, amplitude, and timing of peaks of power and for the presence of an exponential decay of power with increasing frequency. Such decay is typical of normal vesicular breath sounds. Two patients who had the most severe asthma had no exponential decay pattern in their spectra. Other asthmatic patients had exponential patterns in some of their analyzed sound segments, with a range of slopes of the log power vs. log frequency curves from 5.7 to 17.3 dB/oct (normal range, 9.8-15.7 dB/oct). The nonasthmatic wheezing patients had normal exponential patterns in most of their analyzed sound segments. All patients had sharp peaks of power in many of the spectra of their expiratory and inspiratory lung sounds. The frequency range of the spectral peaks was 80-1,600 Hz, with some presenting constant frequency peaks throughout numerous inspiratory or expiratory sound segments recorded from one or more pickup locations. We compared the spectral shape, mode of appearance, and frequency range of wheezes with specific predictions of five theories of wheeze production: 1) turbulence-induced wall resonator, 2) turbulence-induced Helmholtz resonator, 3) acoustically stimulated vortex sound (whistle), 4) vortex-induced wall resonator, and 5) fluid dynamic flutter. We conclude that the predictions by 4 and 5 match the experimental observations better than the previously suggested mechanisms. Alterations in the exponential pattern are discussed in view of the mechanisms proposed as underlying the generation and transmission of normal lung sounds. The observed changes may reflect modified sound production in the airways or alterations in their attenuation when transmitted to the chest wall through the hyperinflated lung.

Adult↗

Gas mixing during high-frequency ventilation: an improved model.

A model for gas transport during high-frequency ventilation incorporating recently derived empirical forms for the effective diffusivity in oscillatory gas flow through a symmetrical branching network is proposed. The model accounts for the movement of gas among airways with changing cross-sectional area by using a moving-reference-frame analysis. The analysis technique incorporates the convective purging of the bias flow at the airway opening. The model predicts that although the cycle-averaged CO2 elimination rate (VCO2) depends most strongly on the product of frequency and tidal volume (VT), VT has an effect on its own, a finding consistent with published observations. This "VT effect" is due primarily to the oscillatory movement of gas from more central regions into peripheral regions where large cross-sectional areas promote efficient CO2 transport by molecular diffusion. Although the VT effect exists independent of the presence of a bias flow, placing the bias flow near the main carina can enhance the VT effect substantially. As VT is increased to values in the range of ordinary tidal breaths, VCO2 predicted by the model achieves close agreement with VCO2 deduced from conventional gas exchange theory.

Biological Transport↗

Influence of the endotracheal tube on CO2 transport during high-frequency ventilation.

Low-volume, high-frequency ventilation (HFV) delivered via an endotracheal tube can maintain eucapnia in both humans and animals. Because recent animal studies have suggested that a substantial fraction of the resistance to gas transport during HFV can be attributed to the presence of the endotracheal tube, we evaluated the importance of the endotracheal tube on carbon dioxide elimination (VCO2) during HFV in humans. We compared the effectiveness of delivering the fresh gas bias flow at the proximal and the distal end of an endotracheal tube. For each bias flow position, we ventilated patients using tidal volumes of 60 ml or less and frequencies from 0.5 to 12 Hz. In each case, VCO2 was approximately 50% greater when the fresh gas was introduced at the carinal end of the endotracheal tube. Thus, the endotracheal tube contributed about one third of the resistance to HFV-induced CO2 transport in these patients. These results indicate that the position of the fresh gas source strongly influences the effectiveness of HFV.

Adult↗

Respiration maintained by externally applied vibration and tracheal insufflation in the cat.

It was reported recently that adequate gas exchange could be maintained in patients and experimental animals by applying very high-frequency (15 Hz), low-volume oscillations at the upper airways. This report deals with a new mode of high-frequency ventilation, in which gas exchange is achieved in paralyzed cats by externally vibrating the chest wall. These vibrations, which alone caused very small-volume (less than 0.5 ml) oscillations at the tracheal opening, maintained gas exchange at normal PaCO2 for hours when coupled with tracheal air insufflation. PaCO2 values as low as 15 torr could be achieved by increasing the insufflation rate. Vibration frequencies in the range of 20-45 Hz were equally effective. The method required little or no continuous positive airway pressure, caused little elevation of mean tracheal pressure, and no consistent changes in arterial and central venous pressures during ventilation. In addition to the potential merits of this method of ventilation, the described vibrations seem to considerably reduce the anatomic dead space and as such may assist conventional methods of artificial ventilation or even spontaneous breathing when rapid and shallow.

Animals↗