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Biomedical subjects

H K Chang

Publications and source records attributed to H K Chang.

At least 109 records · Page 6Linked to original sources

High frequency chest wall oscillation in patients with chronic air-flow obstruction.

In order to assess high frequency chest wall oscillation (HFCWO) as a way to assist spontaneous breathing in obstructive lung disease, we studied 12 patients with severe and stable COPD. HFCWO at 5 Hz were applied by means of an inflatable vest. In order to avoid any discomfort, oscillations were applied only during the expiratory phase of the spontaneous breathing cycle. We compared gas exchange and pattern of breathing during control and HFCWO periods, each lasting 15 min. Minute ventilation did not change, but the pattern of breathing was markedly altered during HFCWO: breathing frequency decreased (p less than 0.001) from 18 +/- 6/min during control to 14 +/- 5/min, whereas tidal volume increased (p less than 0.01) from 600 +/- 200 ml during control to 860 +/- 400 ml. Secondary to this change in the pattern of breathing, arterial PO2 increased slightly (p less than 0.01) from 54 +/- 7 mm Hg during control to 57 +/- 8 mm Hg during HFCWO, and arterial PCO2 significantly (p less than 0.01) decreased from 46 +/- 6 mm Hg during control to 43 +/- 7 mm Hg during HFCWO. In addition, duty cycle (Ti/Ttot) decreased (p less than 0.001) from 0.37 +/- 0.03 s during control to 0.29 +/- 0.05 s during HFCWO. Such a decrease in duty cycle suggest that inspiratory muscle work was facilitated under HFCWO. In 8 patients, we obtained the tension-time index (TTdi), or the product of duty cycle and Pdi/Pdimax, and found that this index significantly decreased (p less than 0.05) from 0.06 +/- 0.03 during control to 0.04 +/- 0.02 during HFCWO.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyspnea↗

Characterization of nucleotide sequence of hepatitis B surface gene and enhancer element of HBV.

The HBV DNA sequence containing a primary part of pre-S2, the coding sequence of the major S protein and the enhancer sequence in pTWS1 was completely sequenced. A comparison with other previously published HBV sequences indicates that the nucleotide sequence homology in the pre-S2 region is 97%, 98% and 98% for adw, adr and ayw subtypes, respectively, and 76% among different subtypes. The nucleotide sequence homology in the major S protein region is 99% for each adw, adr and ayw subtype, and 90% among different subtypes. The important regulatory enhancer sequence (nucleotides 1036-1204) is identical in all subtypes.

Amino Acid Sequence↗

Expression of hepatitis B surface antigen by yeast actin gene promoter.

The promoter sequence (from position -500 to -21) of the yeast actin gene was subcloned into the multiple cloning site of pUC12 to generate a new recombinant plasmid pYAP12. The actin gene promoter can therefore be readily excised from pYAP12 by several restriction enzymes and subsequently placed upstream of the desired protein coding sequence. Results of expression of the hepatitis B surface antigen controlled by the actin gene promoter of pYAP12 in yeast suggest it is a strong functional promoter. To our knowledge, this is the first demonstration of the potential application of the yeast actin gene promoter for expression of foreign proteins in yeast.

Actins↗

Velocity profiles in central airways with endotracheal intubation: a model study.

Steady inspiratory velocity profiles were measured at two flow rates in a 3:1 scale model of the human central airways in the presence of five modes of endotracheal intubation. The presence of an orifice or a short endotracheal tube had no significant effect on the velocity profiles distal to the carina. Long endotracheal tubes change the profiles in both main bronchi. A significant peak occurred in the frontal plane near the walls, and the maximum velocity in the airway was almost identical to the endotracheal tube center-line velocity. The flow impinging on the medial wall of the main bronchus was redirected up around the anterior and posterior walls yielding bipeak velocity profiles in the sagittal plane. A tube placed eccentrically in the trachea over the right main bronchus did not alter the velocity profiles in the left main bronchus, suggesting a redirection of flow over the carina into the left lung. An endobronchial tube at the mouth of the right main bronchus did change the shape of the velocity profiles in the left main bronchus. In the left upper lobar bronchus the presence of trachea intubation had no effect on the velocity profiles. However, in the right upper lobar bronchus, the long endotracheal tube flattened the velocity profiles from the strongly skewed ones seen in the absence of the endotracheal inserts. These results not only are relevant to distribution of ventilation and aerosol particle deposition, but also have strong implications in intrapulmonary gas mixing, especially when high-frequency low tidal-volume ventilation is involved.

Humans↗

Dependence of central airway resistance on frequency and tidal volume: a model study.

The resistance of a hollow cast of human central airways was measured during true sinusoidal airflow oscillations over a wide range of frequencies (0.5-40 Hz) and for various flow amplitudes up to 8 l/s. Pressure and flow were measured in the trachea with high-performance transducers, digitized and averaged over 100 cycles. Data were studied at two points in the flow cycle: at peak inspiratory and expiratory flows and in the two neighborhoods around zero flow where airway resistance (Rv approximately equal to o) was taken as the average slope of the pressure-flow (P-V) curve in each zone. When data obtained near peak flow were plotted in terms of dimensionless pressure drop vs. peak Reynolds number (Rem) and compared with steady-state data, we found no difference up to 2 Hz as previously reported (Isabey and Chang, J. Appl. Physiol. 51: 1338-1348, 1981), a slight decay in pressure drop between 4 and 8 Hz, a frequency-dependent increase in peak flow resistance at high frequencies (10-40 Hz) governed by the Strouhal number alpha 2/Rem beyond alpha 2/Rem = 0.5. On the other hand RV approximately equal to o was found to increase relative to steady state as local acceleration increases, e.g., as peak flow increases at a fixed frequency; this differs from the classical linear theory of oscillatory flow in a long straight tube. To explain these results, we had to use, as in our previous study, an alternative expression for the Strouhal number, i.e., epsilon = L X A X (dV/dt)/V2 (where L and A are the length and cross-sectional area of the trachea and V is a constant flow range over which resistance around flow reversal was computed), which accurately reflects the ratio of local acceleration [d(V/A)/dt)] to convective acceleration [(V/A)2/L] in developing branching flow. Finally, to delineate the regions of dominance of each of the dimensionless parameters, we compiled frequency-tidal volume diagrams for peak flows as well as for reversal. Epsilon, which is negligible near peak flows, appeared to govern the oscillatory P-V relationship near flow reversal in a transitional region of the diagram located between regions of steadiness, or moderate unsteadiness, and a region of dominant unsteadiness governed by alpha.

Airway Resistance↗

Respiratory resistance with histamine challenge by single-breath and forced oscillation methods.

Relaxed expirations were obtained from five anesthetized dogs under control conditions and during various rates of intravenous infusion of histamine. All volume vs. time curves obtained from 20 ms to 2 s after the start of expiration were poorly described by a single exponential function but were fitted very well by a biexponential function. The resistance of the respiratory system as a function of frequency from 2 to 26 Hz was also determined by the forced oscillation method in the same dogs. Three two-compartment models of the respiratory system were identified from the exponentials fitted to the relaxed expiration data, and the one that had the most plausible parameter values under control conditions consisted of a homogeneous lung compartment connected to a viscoelastic compartment. Although a two-compartment model is arguably appropriate for describing relaxed expirations in normal dogs, physiological considerations suggest that there should be more than two interacting components with histamine infusion. We cannot identify all these components from our data, however. The equivalent complex impedance of the respiratory system was also calculated from the biexponential curves and showed significant variation in resistance over the frequency range from 0 to 2 Hz and negligible variation above 2 Hz. The calculated resistances at 2 Hz were consistently higher than those obtained by the forced oscillation method, which may be due to the nonlinear behavior of the respiratory system during relaxed expiration. We conclude that the single-breath and forced oscillation methods should be viewed as providing complimentary information about respiratory resistance.

Airway Resistance↗

High frequency transthoracic ventilation improves gas exchange during experimental bronchoconstriction in rabbits.

In order to evaluate the efficacy of ventilation by high frequency transthoracic oscillation in obstructive lung disease, we studied 10 anesthetized and paralyzed rabbits during experimental bronchoconstriction. In order to generate body surface oscillation, the animals were placed in a body-box connected to a piston pump. Two frequencies were successively applied in random order: 1 Hz, representing "conventional" ventilation, and 5 Hz for high frequency ventilation. During the control period, the magnitudes of the oscillation were adjusted such that the tidal volumes thus produced yielded normocapnia (PaCO2 = 40 +/- 2 mmHg) for at least 3 min at each frequency. The same tidal volumes were then used after a bronchoconstriction induced by aerosolized carbachol. We obtained a severe and stable bronchoconstriction and oscillated the animals at 1 and 5 Hz at identical tidal volumes as those used during the control period. Identical at the 2 frequencies of oscillation during the control period, the rate of CO2 elimination with bronchoconstriction was significantly higher (p less than 0.05) at 5 Hz (15.9 +/- 3.3 ml/min) than at 1 Hz (14.2 +/- 3.9 ml/min); PaCO2 was also significantly lower at 5 Hz than at 1 Hz. Mean arterial PO2 was significantly higher (p less than 0.01) at 5 Hz (58 +/- 4 mmHg) than at 1 Hz (46 +/- 12 mmHg) during bronchoconstriction. Mean alveolararterial O2 pressure difference was significantly lower (p less than 0.01) at 5 Hz (49 +/- 13 mmHg) than at 1 Hz (59 +/- 11 mmHg). Only a minor increase in lung volume was found during high frequency ventilation, and no significant hemodynamic changes occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

High-frequency chest wall oscillation. Assistance to ventilation in spontaneously breathing subjects.

In five supine normal subjects breathing spontaneously, we studied the effects of high-frequency chest wall oscillation (HFCWO), which was achieved by oscillating the pressure in an air-filled cuff wrapped around the lower thorax. Oscillations of 3.5 and 8 Hz (in randomized order) were applied for 15 minutes each at both maximal (mean of 90 to 102 cm H2O) and half-maximal peak tolerable cuff pressures. Fifteen minutes of control spontaneous ventilation preceded each HFCWO maneuver. The HFCWO resulted in a significant decrease in spontaneous minute ventilation (VES) at maximal and half-maximal pressures by 35 and 40 percent, respectively, at 3 Hz and by 26 and 35 percent, respectively, at 5 Hz, with little change in VES at 8 Hz. This occurred despite an unchanging arterial carbon dioxide tension at all frequencies. Arterial oxygen pressure increased at 3 Hz at maximal pressure but remained statistically unchanged at 3 Hz at half-maximal pressure and at 5 Hz and 8 Hz both at maximal and half-maximal pressures. We conclude that HFCWO may potentially assist ventilation in spontaneously breathing man without requiring an endotracheal tube.

Adult↗

The rectilinear pressure-flow relationship in the pulmonary vasculature: zones 2 and 3.

To elucidate the significance of the rectilinear pressure-flow relationship of the pulmonary vasculature under zone 2 and 3 conditions, isolated left lower lobes of dog lungs were perfused at different flow rates under the two zone conditions. The lobar arterial pressure (Pa) was measured directly, whereas the pressures in the peripheral end of the arteries (Pa') and veins (Pv') were measured with the arterial and venous occlusion (AVO). We thus obtained three pressure-flow relationships: Pa-Q, Pa'-Q and Pv'-Q. From these relationships the contribution of each of the three segments (defined by the arterial and venous occlusion) to the slope and intercept of the Pa-Q relationship was determined. To a first approximation, in zone 3 the ohmic resistance was mainly in the arterial and venous segments, whereas the Starling resistance, although small, was equal in the three segments. In zone 2 (Palv = 15 mm Hg) the Starling resistance increased markedly in the middle segment. Because zone 3 and 2 conditions can co-exist within the lung, a simple three-segment model to represent the pulmonary vasculature was inadequate to explain all the pressure-flow data and therefore was modified to include two parallel channels one of which contains a critical closing pressure (Pc). Such a model implies that two different driving pressures determine the total flow: in vascular channels where Pc greater than Pv (outflow venous pressure) flow is determined by Pa-Pc gradient, and in channels were Pc less than Pv flow would be determined by the Pa-Pv gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pressure change and gas mixing induced by oscillations in a closed system.

In an attempt to delineate some mechanical behaviors found in branching airways, pressure transmission, gas motion, and mixing were studied during high-frequency oscillation (HFO) in an idealized system consisting of a large straight tube and a rigid sphere linked together by a small straight tube. Depending on the frequency f, and on the unsteadiness dimensionless parameter alpha, pressure amplitude in the large tube is either strongly attenuated or amplified in the sphere. This finding may provide a theoretical basis for the pressure resonance phenomenon observed in the lung by previous investigators. Gas compression in the closed volume causes convective mixing throughout the system. The measured dispersion was found to be proportional to f(VT/A)2, in agreement with a recent report. However, bulk convective mixing was sufficient to explain the dispersion for oscillatory volumes (VT) as small as 80 percent of the small tube volume, as has been previously suggested.

Biomechanical Phenomena↗

Effect of hematocrit on vascular pressure profile in dog lungs.

We studied the effect of blood hematocrit (Hct) on the longitudinal distribution of pulmonary vascular pressure profile in an in situ isolated left lower lobe preparation of dog lung using the arterial and venous occlusion technique. The total arteriovenous pressure drop (delta PT) across the lobe was partitioned into pressure drops across an arterial (delta Pa), a venous (delta Pv), and a middle segment (delta Pm). Three levels of Hct were studied: low (18 +/- 5%), normal (41 +/- 4%), and high (66 +/- 5%). Arterial and venous occlusions were performed under constant-flow or constant-pressure perfusion. When flow was maintained constant, the increase in delta PT between low and normal Hct was due to increases in delta Pa, delta Pm, and delta Pv; however, between normal and high Hct, the increase in delta PT was primarily due to an increase in delta Pm. When delta PT was kept constant by adjusting flow, changes in delta Pa and delta Pv were in the same direction as changes in blood flow rate but in opposite direction to changes in Hct. In contrast, changes in delta Pm were in the same direction as changes in Hct. The results showed that the vascular resistance of the middle segment ranged from 7% of total pulmonary vascular resistance at low Hct to 53% at high Hct, suggesting that the vessels within this segment offer the greatest impairment to the transit of blood cells.

Animals↗

Effect of the larynx on oscillatory flow in the central airways: a model study.

Measurements were made of the effect of the larynx on the oscillatory flow profiles in a 3:1 scale model of the human central airways. A fixed glottic aperture corresponding to the shape and size at midinspiration was used. Oscillatory airflows at peak Reynolds numbers, similar to those obtained during spontaneous breathing and panting, were studied. The flow distribution to the five lobar bronchi was maintained by distally placed linear resistors. A hot-wire anemometer probe was used to measure the local velocity along two perpendicular diameters at six stations distributed through the model. Near the proximal end of the trachea, the flat velocity profiles at the beginning of the flow cycle peaked at maximum flow because of the jet created by the glottic aperture. This peaked structure was conserved during the latter half of the inspiratory cycle. Close to the carina, the jet had almost dissipated and the entry conditions into the main bronchi corresponded to those in the absence of the laryngeal model. The effect of the glottic aperture on the mean velocity was not felt beyond the carina, and the characteristic skewed profiles seen in oscillatory flows, in the absence of the larynx, were present in the main and lobar bronchi.

Humans↗

Segmental pulmonary vascular resistance in progressive hydrostatic and permeability edema.

We used the in situ blood-perfused left lower lobe preparation of the dog to examine the effect of hydrostatic and permeability edema on the slope and intercept of the vascular pressure-flow (P/Q) relationship and on the longitudinal distribution of vascular resistance with the arterial and venous occlusion technique. Hydrostatic edema (HE) was induced by raising the venous pressure, and permeability edema (PE) was induced with alpha-naphthylthiourea. When the hematocrit (Hct) of the perfusate was kept normal (approximately 40%), HE had no significant effect on either the slope or the intercept of the P/Q relationship or on the distribution of vascular resistance. PE caused a small increase in the intercept of the P/Q relationship and a small rise in the resistance of the vessels in the middle segment. In another series of HE experiments in which Hct was allowed to increase during edema formation, there was a marked increase in vascular resistance. We conclude that edema per se does not increase vascular resistance significantly and that the increases in vascular resistance which were observed previously by other investigators in the isolated lungs may be due to increases in blood hematocrit.

Animals↗

Respiratory resistance in dogs by the single-breath and the forced oscillation methods.

Total respiratory resistance (Rrs) was measured in six anesthetized dogs with two different methods: the single-breath (SB) method, which provides the time constant of the system during a relaxed expiration and the forced oscillation (FO) method, which uses a pseudorandom noise signal applied at the airway opening. The comparison was made in three conditions: before muscle paralysis (A), after muscle paralysis (B), and after tracheal banding (C). In conditions A and B the two computed resistances correlated very well with each other (r = 0.98). No systematic difference between Rrs values obtained with the two methods was found. In condition C the respiratory resistance was clearly nonlinear from the flow-volume curves during SB and could be described with Rohrer's equation: Rrs = K1 X V + K2 X V2, where K1 and K2 are Kohrer's constant and V is flow. Rrs measured with FO was not frequency dependent during tracheal banding (C) and was virtually equivalent to K1. Since the FO method uses low flows as the input of the respiratory system and K1 could be ascribed to laminar flow, the numerical matching appears reasonable and tends to reinforce the validity of both methods of measurement. We conclude that, for the normal respiratory system, FO and SB methods are approximately equivalent. In the presence of a markedly alinear central airway resistance with normal lungs, the SB method appears to provide a more adequate description of the flow-resistive properties of the system.

Airway Resistance↗

Stable normocapnia during high-frequency body surface oscillation in rabbits.

In order to identify the useful range of frequencies and the effect of lung volume on gas exchange during high-frequency ventilation, particularly during high-frequency body surface oscillation (HFBSO), we studied 12 normal, anesthetized, and paralyzed adult rabbits in 2 groups at 1, 3, 5, 8, 12, and 16 Hz in random order. The rabbits were placed in a body box, and a "bias" flow system different from all previously reported systems was used. For a given animal at a given frequency, the oscillation magnitude was adjusted to ensure normocapnia, defined as PaCO2 equal to 40 +/- 2 mmHg, for at least 5 min. For the first group (n = 6) with a mean tracheal pressure of 0.5 cmH2O, the necessary tidal volumes (mean +/- SD) were 3.7 +/- 0.2, 1.9 +/- 0.2, and 1.5 +/- 0.1 ml/kg at 1, 3, and 5 Hz, respectively. Further increases in frequency resulted in only small decreases in the required tidal volumes: 1.4 +/- 0.1, 1.2 +/- 0.1, and 1.2 +/- 0.1 ml/kg at 8, 12, and 16 Hz, respectively. Arterial PO2 values were very similar at all 6 frequencies, with a mean of 78.6 +/- 3.3 mmHg in this group. For the second group (n = 6) with a mean tracheal pressure of 5 cmH2O, arterial PO2 values were again the same at all frequencies applied but were significantly higher (95.5 +/- 2.6 mmHg) than in the first group. No significant difference was observed in the tidal volumes required to maintain normocapnia between the 2 groups, i.e., at the 2 mean tracheal pressures studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nitrogen washout during tidal breathing with superimposed high-frequency chest wall oscillation.

In order to assess the efficacy of high-frequency chest wall oscillation (HFCWO) superimposed on tidal ventilation, multiple-breath nitrogen washout curves were obtained in 7 normal seated subjects. To maintain a regular breathing pattern throughout the study, the subjects breathed synchronously with a Harvard ventilator set at a constant tidal volume and frequency for each subject during a trial period. Washout curves were obtained during 3 different maneuvers performed in random order. Series A was the control condition with no superimposed HFCWO. In Series B and C, HFCWO at 5 Hz was superimposed on the regulated tidal breathing; the magnitude of the oscillatory tidal volume measured at the airway opening was 20 ml for Series B and 40 ml for Series C. The nitrogen washout was clearly faster in Series C than in Series A for each subject. In Series B, there was an interindividual variability, with a washout rate either equal to that in Maneuver A or in Maneuver C, or intermediate between the two. When these washout curves were analyzed in terms of a simple monocompartment model, the time constant of the washout was found to decrease by 16 +/- 11% in Series B, and 25 +/- 7% in Series C compared with that in Series A. In this group of normal subjects, the correction of any inhomogeneity in the distribution of the ventilation is unlikely to explain these results because of the close fit of all washout curves to a monoexponential model. It is postulated that during inspiration HFCWO enhances gas mixing in the lung periphery and that during expiration it improves gas mixing in the airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Model study of flow dynamics in human central airways. Part III: Oscillatory velocity profiles.

Measurements of oscillatory velocity were made in a 3:1 model of the human central airways. The model was built of acrylic plastic and mounted vertically. A reciprocating pump connected to the upper end of the model privided oscillatory flow frequencies of 0.25, 1, 2 and 4 Hz (equivalent to 2.25, 9, 18 and 36 Hz in the actual airways) and tidal volumes of 300, 500 and 1500 ml. A hot-wire anemometer probe was used to measure velocities along two perpendicular diameters and at six stations distributed through the model. The flow distribution through the five lobar bronchi was controlled by distally positioned linear resistors . The measurements indicate that the entry flow profile into the model during oscillatory flow was essentially flat. At low frequencies, the velocity profiles attained at peak flow rate resemble the profiles seen under steady flow conditions at the corresponding Reynolds number. In the frontal plant these profiles are asymmetric with a maximum in velocity directed towards the outer wall of the bend. In the sagittal plane the velocity profiles are symmetric and have the characteristic bi-peak (M-shaped) structure seen in the steady flows. However, as the frequency increases the velocity profiles throughout most branches tend to flatten except in the right upper lobar bronchus where the skewed velocity profiles persist even at the highest frequencies studied. As in steady flows the nature of the velocity profile is strongly influenced by the airway geometry. Furthermore, the peak velocity profiles resemble steady flow profiles at comparable Reynolds numbers up to a Womersley number of 16.

Biomechanical Phenomena↗

High-frequency ventilation: a review.

As a new mode of assisted ventilation, high-frequency ventilation (HFV) embodies several types of devices, all of which employ tidal volumes much smaller and frequencies much greater than conventional mechanical ventilation (CMV). Due to the smaller swings of airway pressure during HFV, it is thought that some of the drawbacks of CMV may be overcome. Besides the obvious clinical implications, considerable interest has been generated concerning the physiological effects of HFV. In this review, the effects of HFV on gas exchange, lung mechanics, mucociliary transport, cardiovascular function and control of breathing will be examined. Although the role of HFV in the management of different lung diseases is still unclear, it has proved to be both a strong stimulus and a useful tool in the study of physiology.

Animals↗