Effect of valve closure time on the determination of respiratory resistance by flow interruption.
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Airway Resistance↗
Biomedical subjects
J H Bates
Publications and source records attributed to J H Bates.
The effect of a proximal compliance on interrupter measurements of resistance.
The interrupter method for measuring respiratory system resistance involves rapidly interrupting flow at the airway opening while measuring the pressure just distal to the site of interruption. In general, the pressure signal obtained exhibits an initial rapid change (delta Pinit) accompanied by rapid damped oscillations, followed by a further slow change to a steady-state plateau level. Delta Pinit is thought to principally reflect the resistance of the pulmonary airways Raw. We have developed a computer model capable of simulating the main features observed in an interrupter pressure signal. We show that the distinct phases in the pressure signal can be obscured by the existence of a compliant compartment between the airways and the occluding valve (e.g. the cheeks and pharynx) when Raw is increased. Our results suggest that supporting the cheeks may enable one to estimate Raw with the interrupter technique in the presence of mild to moderate bronchoconstriction, but that with severe bronchoconstriction (Raw increased 10-fold above normal) it may not be possible.
Adult↗
Frequency-dependent effects of hypercapnia on respiratory mechanics of cats.
The effect of increasing arterial partial pressure of CO2 (PaCO2) on respiratory mechanics was investigated in six anesthetized, paralyzed cats ventilated by constant-flow inflation. Respiratory mechanics were studied after end-inspiratory occlusions. Zero frequency resistance (Rmax), infinite frequency resistance (Rmin), and static elastance (Est) were calculated for the respiratory system, lung, and chest wall. Alveolar ventilation was manipulated by the addition of dead space to achieve a range of PaCO2 values of 29.3-87.3 mmHg. Cats did not become hypoxic during the experiment. Under control conditions marked frequency dependence in Rmax, Rmin, and Est of the respiratory system, lungs, and chest wall was demonstrated. The chest wall contributed 50% of the total resistance of the respiratory system. With increasing PaCO2 the only resistance observed to increase was Rmax of the lung (P less than 0.01). There were also no changes in the static elastic properties of either the lungs or the chest wall. These results suggest that hypercapnia increases resistance by changes in the lung periphery and not in the conducting airways.
Animals↗
Partitioning of airway responses to inhaled methacholine in the rat.
We measured the changes in upper and lower airway resistance after inhalation of aerosols of methacholine (MCh) in doubling concentrations (16, 32, 64, and 128 mg/ml) in 11 anesthetized nonintubated spontaneously breathing rats. Upper airway resistance (Ru) increased from a control value of 0.48 +/- 0.04 cmH2O X ml-1 X s (mean +/- SE) to 0.85 +/- 0.15 after 128 mg/ml MCh, whereas lower airway resistance (Rlo) increased from 0.11 +/- 0.03 to 0.21 +/- 0.04. However, there was no correlation between the magnitudes of the changes in Ru and Rlo. In a further seven anesthetized spontaneously breathing rats aerosols of MCh were delivered into the lower airways via a tracheostomy and resulted in increases in Rlo from a control value of 0.20 +/- 0.03 to 0.66 +/- 0.12 after 128 mg/ml MCh. Ru also increased to approximately double its control value. We conclude that inhaled MCh causes narrowing of both Ru and Rlo in the anesthetized rat, the changes in Ru and Rlo are not correlated, and changes in Ru can occur when MCh deposition occurs only in the lower airways.
Aerosols↗
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↗
Methacholine-induced airway reactivity of inbred rats.
Dose-response curves to inhaled aerosolized methacholine chloride (MCh) were obtained in anesthetized spontaneously breathing rats. Thirty rats (10/strain), randomly selected from highly inbred ACI, Lewis (L), and Brown Norway (BN) strains and 40 rats (20/strain) from similarly inbred Wistar-Furth (WF) and Buffalo (Buf) strains were studied. Airway responses were quantitated from changes in pulmonary resistance (RL) and airway reactivity was calculated as the dose of MCh required to increase RL to 150% (ED150RL) and 200% (ED200RL) of base line. There were no statistically significant differences in ED150RL and ED200RL among the five rat strains. Large interindividual variability was present as evidenced by 128-fold differences in ED150RL and ED200RL between the least and most sensitive animal of the same strain. In contrast, seven animals studied repeatedly on different days had values of ED150RL that differed by an average of only 2.9-fold (range 1.6-5.3). Thirteen rats that were studied on two occasions separated by an interval of 3 mo showed no systematic changes in airway reactivity. We conclude that airway reactivity to inhaled methacholine in anesthetized nose-breathing rats is not strain related, and despite animals of a given strain being genetically identical, the variability in airway reactivity within strains suggests that environmental rather than genetic factors are the major determinants of that reactivity.
Airway Resistance↗
Genetic relatedness among strains of the Mycobacterium tuberculosis complex. Analysis of restriction fragment heterogeneity using cloned DNA probes.
Chromosomal DNA isolated from 3 reference and 2 clinical isolates of Mycobacterium tuberculosis, 2 reference strains each of M. bovis and M. bovis BCG, and 1 reference strain of M. kansasii, was digested with 9 restriction endonucleases. The restriction fragments were analyzed by agarose gel electrophoresis. With each enzyme tested the patterns of the strains of M. tuberculosis, M. bovis, and M. bovis BCG were indistinguishable but clearly distinct from those of M. kansasii. A library of M. tuberculosis H37Rv DNA was prepared by cloning Bam HI digest fragments into lambda 1059. Eight randomly selected clones, having multiple Bam HI sites, were used to probe restriction digests of DNA from the strains of the tuberculosis complex. Two of the cloned segments hybridized with homologous fragments in 4 different enzyme digests of all strains. With 2 clones, hybridization differed among the strains; however, some homologous sequences were detected. With 4 clones, efficient hybridization occurred only with M. tuberculosis H37Rv DNA. These hybridization results indicate that some regions of the chromosome are highly conserved among members of the tuberculosis complex, whereas others are diverged. Selected DNA probes were useful in detecting differences among strains of the tuberculosis complex.
Cloning, Molecular↗
Analysis of plasmids in Mycobacterium avium-intracellulare isolates from persons with acquired immunodeficiency syndrome.
Twenty-six strains of the Mycobacterium avium complex isolated from persons with AIDS were examined for plasmid content. The strains were of serotypes 4, 8, 4/6, and 4/8. Plasmid content was determined by agarose gel electrophoresis. All 26 strains carried small plasmids (9 to 15 Mdal), with 11 strains carrying 1 small plasmid and 15 carrying 2. Ten strains also carried large plasmids (greater than 100 Mdal), and 1 strain carried a 60 Mdal plasmid. We have reported molecular cloning of plasmid pLR7, a small plasmid derived from a serotype 4 strain. Cloned segments of pLR7 were used as hybridization probes to detect homologous plasmids in the AIDS-associated strains. Each of the 26 strains carried a plasmid closely related to pLR7. Considerable heterogeneity of size and restriction sites was observed. The finding of plasmids in all strains raises the possibility that they may play a role in virulence. The plasmids will serve as a useful marker for epidemiology and might be useful as probes for detecting M. avium-intracellulare in clinical material.
Acquired Immunodeficiency Syndrome↗
A model-free way of representing hyperthermia cell survival data.
We present a method of fitting curves to cell survival data that is free from all model assumptions, requiring only that the fitted curves be decreasing and reasonably smooth, where the degree of smoothness is determined from considerations of experimental error. The fitted curves are then differentiated to yield frequency distributions of cell killing times, which may be of value in defining subpopulations with different sensitivities to the cytotoxic agent under study. In addition, confidence intervals on the fitted curves and frequency distributions are obtained by Monte Carlo simulation. The results allow the objective and model-free assessment of the effects of various experimental interventions on cell survival.
Cell Survival↗
Thermal adaptation in CHO cells at 40 degrees C: the influence of growth conditions and the role of heat shock proteins.
The kinetics of thermal adaptation at the nonlethal temperature of 40 degrees C was studied in CHO (Chinese hamster ovary) cells in vitro. Thermal resistance, demonstrated as an increase in mean 45 degrees C killing time or as an increase in the shoulder of the 45 degrees C survival curve, was fully developed by 2 h. Control cells in early logarithmic phase were more heat sensitive than those in stationary phase. Corresponding 45 degrees C killing time frequency distributions were unimodal with an increase in mean killing time from early logarithmic to stationary phase. Cells which were thermally adapted at 40 degrees C for 6 h had biphasic 45 degrees C killing time frequency distributions, and as cells progressed from early logarithmic to stationary phase the heat-sensitive subpopulation progressively declined. Exposure to 40 degrees C produced a 30% increase in total protein synthesis. Proteins with molecular weights 72, 89, and 109 kDa which correspond to those induced by lethal heat shock were synthesized at 40 degrees C, but there was no close temporal correlation between the development of heat resistance at 40 degrees C and synthesis of the heat shock proteins. Cycloheximide (100 micrograms/ml) reduced the mean 45 degrees C killing time but did not totally prevent the development of heat resistance at 40 degrees C.
Adaptation, Physiological↗
A polynomial method for fitting continuous distributions of exponentials with positivity constraint.
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Animals↗
Effect of mechanical loading on displacements of chest wall during breathing in humans.
Using a respiratory inductive plethysmograph (Respitrace) we studied thoracoabdominal movements in eight normal subjects during inspiratory resistive (Res) and elastic (El) loading. The magnitude of loads was chosen so as to produce a fall in inspiratory mouth pressure of 20 cmH2O. The contribution of rib cage (RC) to tidal volume (VT) increased significantly from 68% during quiet breathing (QB) to 74% during El and 78% during Res. VT and breathing frequency did not change significantly. During loading a phase lag was present on inspiration so that the abdomen led the rib cage. However, outward movement of the abdomen ceased in the latter part of inspiration, and the RC became the sole contributor to VT. These observations suggest greater recruitment of the inspiratory musculature of the RC than the diaphragm during loading, although changes in the mechanical properties of the chest wall may also have contributed. Indeed, an increase in abdominal end-expiratory and end-inspiratory pressures was observed in five out of six subjects, indicating abdominal muscle recruitment which may account for part of the reduction in abdominal excursion. Both Res and El increased the rate of emptying of the respiratory system during the ensuing unloaded expiration as a result of a reduction in rib cage expiratory-braking mechanisms. The time course of abdominal displacements during expiration was unaffected by loading.
Abdominal Muscles↗
Analysis of the behavior of the respiratory system with constant inspiratory flow.
For a respiratory system with constant compliance and resistance a constant flow can occur during part or all of inspiration in two situations: when the flow is constrained to be constant throughout inspiration, such as is the case with some mechanical ventilators, and when the applied pressure is a ramp (i.e., increasing constantly with time), which may occur during mechanical ventilation and spontaneous breathing. After initial transients in pressure and flow, respectively, have decayed away both situations result in linear volume-time and pressure-time relationships. The slope of the corresponding pressure-volume line then yields an estimate of the total compliance of the respiratory system, and the intercept, divided by the constant flow, provides the total resistance. We have shown theoretically that, for a model composed of two compartments in parallel, the total compliance is the same as the static compliance and equals the sum of the compliances of the two compartments. Furthermore, this compliance is independent of the breathing frequency. However, the total resistance is, in general, a function of both the resistances and the compliances. When the time constants of the two compartments are equal the total resistance assumes its minimum value and becomes independent of the compliances. This minimum value of resistance can be obtained, regardless of the time constants, by dividing the immediate drop in airway opening pressure, obtained after occluding during steady state inspiration, by the inspiratory flow.
Airway Resistance↗
Volume-time profile during relaxed expiration in the normal dog.
Airway opening pressure, esophageal pressure, and flow were obtained during relaxed expirations in two normal anesthetized paralyzed dogs. The signal-to-noise ratio in the flow signals was greatly increased by averaging 10 different signals obtained with the same lung inflation volume. Numerical integration of an averaged flow signal then yielded the time course of the volume of the respiratory system above functional residual capacity (the elastic equilibrium volume). Comparison of volume signals obtained with different inflation volumes suggests that the resistance of the respiratory system increases with flow. The flow-volume and semilog volume curves show that expiration is induced by two apparently separate mechanisms: one causes emptying of most of the expired volume over a time interval of much less than 1 s, whereas the other contributes a relatively small amount to the expired volume over a significantly longer time (greater than or equal to 1 s). We postulate the first mechanism to be due to that of the respiratory system behaving like a single unit, with an elastance that is slightly volume dependent, emptying through a single airway which has a resistance that increases with flow. From the nature of airway opening pressure and esophageal pressure measured after occlusion in midexpiration, we conclude that the second mechanism is due to the viscoelastic properties (i.e., creep) of the respiratory system. The properties are manifest mainly in the chest wall.
Animals↗
Phage typing of the Mycobacterium avium-intracellulare-scrofulaceum complex. A study of strains of diverse geographic and host origin.
A total of 339 strains of the Mycobacterium avium-intracellulare-scrofulaceum complex were phage typed using our previously described technique and 11 typing phages. These included 235 strains of human origin obtained from state health laboratories in Virginia, Georgia, Florida, and Arkansas, 26 strains isolated from persons with AIDS, 38 strains isolated from animals, and 40 environmental isolates. A phage-typing scheme was developed that denotes sensitivity to 8 primary typing phages: the JF group (JF1, JF2, JF3, and JF4), phage D302, and the AN group (AN3, AN9, and AN1-8). The 3 auxiliary phages (VC3, VA6, and D32) define subgroups of the strains sensitive to the AN phages. A total of 99 strains were sensitive to at least 1 phage. Of 31 serotype 1 or 2 strains from animals, 13 were sensitive to AN phages but resistant to JF phages. In contrast, 7/33 serotype 4 or 8 strains from animals or from persons with AIDS were sensitive to JF phages but not to the AN phages. Of the clinical isolates not associated with AIDS, 78/235 were phage sensitive. These strains could be divided roughly into 4 groups: sensitive to AN phages, sensitive to JF phages, sensitive to phage D302, and sensitive to multiple phages. Only 1 of the environmental isolates was phage sensitive. The results indicate that phage typing can subdivide this heterogeneous group of organisms and is a useful tool for epidemiological studies.
Acquired Immunodeficiency Syndrome↗
Effects of thermal adaptation at 40 degrees C on membrane viscosity and the sodium-potassium pump in Chinese hamster ovary cells.
We have demonstrated increased heat resistance in Chinese hamster ovary cells grown to confluence at 37 degrees C and thermally adapted at the nonlethal temperature of 40 degrees C for 24 h. Membrane viscosity, estimated by fluorescence anisotropy, was inversely related to temperature, from 5 degrees C to 45 degrees C. For a given temperature viscosity was consistently higher in thermally adapted cells than in native cells. Having demonstrated a change in membrane structure associated with thermal adaptation, we carried out a study of the Na+-K+ pump in native and thermally adapted cells as an example of a vital active transport process known to be sensitive to membrane viscosity. 86Rb uptake measured from 31 degrees C to 50 degrees C increased steadily to 46 degrees C and then decreased rapidly in both native and thermally adapted cells. Detailed measurement of ouabain-sensitive 86Rb influx demonstrated an increase in both Km and Vmax between 37 degrees C and 45 degrees C, but there was no difference between native and thermally adapted cells. We have thus demonstrated an adaptive structural change in the cell membrane of mammalian cells which may be related to the induction of thermal resistance at 40 degrees C but which is not associated with any change in this active transport system.
Adaptation, Physiological↗
Restriction endonuclease mapping and cloning of Mycobacterium intracellulare plasmid pLR7.
A restriction map of Mycobacterium intracellulare plasmid pLR7 was developed. This 15.3-kb plasmid had unique sites for BamHI, HindIII, and XbaI. Various large fragments of pLR7 were cloned into pBR322 or pHP34 and propagated in Escherichia coli. A hybrid pLR7 ::pBR322 plasmid carrying the complete pLR7 sequence was constructed by joining the plasmids at their HindIII sites. The construction of these hybrids will facilitate the analysis and manipulation of pLR7 and may allow the development of this plasmid as a model system for genetic analysis in mycobacteria.
Chromosome Mapping↗
Characterizing and correcting for the dynamic response of a bag-in-box system.
A bag-in-box system (BBS) whose volume is monitored by a mechanical spirometer tends to have a slow response if the volume of the box is large, and this may significantly affect its measurement of gas flow. We describe a device for creating reproducible gas flows with which the impulse response of a BBS may be conveniently determined. Two computational techniques for correcting a BBS flow measurement for the effects of the impulse response were investigated: 1) an exponential model method that assumes a second-order model of the BBS dynamics and 2) a Fourier transform-based method of deconvolution known as Wiener filtering. Both correction methods produced a significant increase in the accuracy of BBS flow estimations, with the Wiener filter giving superior results.
Respiratory Function Tests↗