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Biomedical subjects

J Milic-Emili

Publications and source records attributed to J Milic-Emili.

At least 145 records · Page 8Linked to original sources

Non-invasive measurement of respiratory mechanics in ICU patients.

Recent methods developed for non-invasive determination of the mechanical properties of the respiratory system have been reviewed. These methods can provide valuable on-line information in patients mechanically ventilated in the intensive care unit setting. More extensive use of such methods should help to provide a better understanding of the physiopathologic processes and adaptive mechanisms present in patients who require mechanical ventilation.

Adult↗

Metabolic and ventilatory responses during very low level exercise.

1. Nine male and six female healthy subjects were studied during supine bicycle exercise at workloads of 12 and 37 W; pedalling rates varied between 30 and 50 cycles/min at each workload. Measurements were made of oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), tidal volume (VT), respiratory frequency (fR), inspiratory and expiratory time (TI, TE) and mean inspiratory flow (VT/TI) using a non-invasive canopy-computer-spirometer system. 2. At rest, males had greater values of VE, VT, TI, inspiratory duty cycle (TI/TTOT), VCO2 and VO2, and a lower fR, than females. 3. At the lower workload, VO2, VCO2, VE, VT and VT/TI increased linearly with increasing pedalling rate, whereas at the higher workload there was a decrease in VO2 and little or no change in ventilatory parameters from 30 to 50 cycles/min except for an increase in fR in females. 4. While performing supine exercise, there was an effect of pedalling rate on ventilatory and metabolic parameters at the low workload (12 W) which diminished at the higher workload (37 W). An increase in pedalling rate appears to enhance efficiency at these low workloads. 5. Differences between the sexes during exercise generally include: (a) a higher breathing frequency, (b) a greater mechanical efficiency, and (c) lower ventilatory equivalents of O2 and CO2 (VE/VO2 and VE/VCO2) during the higher workload in females than males.

Adult↗

Does interstitial lung edema compress airways and arteries? A morphometric study.

We compared areas and diameters of small airways and arteries in three groups of anesthetized dogs: 1) control (n = 5), 2) hydrostatic edema induced by fluid overload (n = 13), and 3) increased permeability edema induced with alpha-naphthylthiourea (n = 5). We measured pulmonary arterial and wedge pressures in all groups and cardiac output in the hydrostatic edema group. Postmortem, lobes were frozen at functional residual capacity and samples taken for measurements of extravascular lung water (Qwl/dQl) and for light microscopy. We also examined lobes from hydrostatic edema experiments fixed at transpulmonary pressures of 5 and 27 cmH2O. From the histology slides, bronchovascular bundles with respiratory bronchioles (n = 706) and bronchioles (n = 467) were photographed and airway and vessel areas and diameters measured. Alveolar and airway luminal edema were graded. We found that only in hydrostatic edema, pulmonary arterial and wedge pressures increased and vascular resistance fell with fluid infusion. Mean Qwl/dQl values were 3.80 +/- 0.17, 6.81 +/- 0.96, and 9.34 +/- 0.62 (SE) in control, hydrostatic, and increased permeability edema groups, respectively. By quantitative histology, airway and arterial areas and diameters did not decrease in edema and rose with increasing transpulmonary pressure. Variable quantities of air-space edema were seen. We conclude that interstitial edema does not compress small airways or arteries and that other mechanisms, including alveolar and airway luminal edema, may explain reported increases in airway resistance.

Animals↗

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↗

Load compensation during positive pressure breathing in anesthetized man.

To investigate the mechanisms by which human subjects prevent or compensate for the change in respiratory muscle length imposed by applying continuous positive pressure to the airways, six men were studied under general anesthesia with methoxyflurane at the end of a minor surgical procedure (rhinoplasty). Ventilatory and occlusion pressure response to carbon dioxide was measured by a rebreathing technique with no bias pressure, or with 16 cm H2O positive pressure produced by adding weights to a spirometer bell. Static pressure-volume curves of the respiratory system were obtained while the subjects were paralyzed with succinyl choline. In contrast to awake subjects described in other studies, the anesthetized patients did not activate expiratory muscles to combat the rise in end-expiratory level caused by pressure, and showed little evidence of enhanced activation of inspiratory muscles that in the conscious state compensates for the disadvantage of their shorter length. A change in the shape of the occlusion pressure wave, however, suggested that positive pressure had some effect on the neural discharge to inspiratory muscles. The mechanisms by which the respiratory system defends itself against a pressure load that tends to change end-expiratory level are sensitive to anesthesia and may require consciousness.

Adult↗

The effects of posture on the metabolic and ventilatory response to low level steady state exercise.

Low level exercise is frequently used to assess cardiac and pulmonary function. This study examines the differences in both metabolic and respiratory patterns between the sitting and supine position. Six normal male subjects were studied in both positions during four levels of exercise (12.5, 25, 37.5 and 50 W). Oxygen consumption (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were greater when sitting as were the ventilatory equivalents to O2 (VE/VO2) and CO2 (VE/VCO2). Respiration was compared at equivalent workloads; the greater minute ventilation observed during sitting was due to greater tidal volumes (VT) and mean inspiratory flows (VT/TI). Expiratory time (TE) was longer and inspiratory duration shorter under most conditions when sitting. When breathing patterns were compared at similar degrees of minute ventilation, VT, TE and VT/TI were greater when sitting, while respiratory frequency (fR) was slower.

Carbon Dioxide↗

The metabolic and ventilatory response to the infusion of stress hormones.

Sepsis and trauma result in increases in epinephrine, glucagon, and cortisol secretion as well as alterations in respiratory pattern that is characterized by increased minute ventilation, decreased tidal volume, and increased frequency. Six male subjects were infused for 5.5 hours with cortisol, epinephrine, and glucagon in amounts designed to simulate plasma levels seen in patients following trauma. During the initial 20 minutes of the hormone infusion, minute ventilation (VE), oxygen consumption (VO2), and carbon dioxide production (VCO2) increased above preinfusion values. VCO2 increased more than VO2 resulting in an increase in respiratory quotient (RQ) from 0.93 to 1.14. The increase in VE was due to increased tidal volume and not frequency (f). After 4.5 hours, the VE, VO2, and VCO2 were still above preinfusion levels but the RQ had decreased to 0.98 because of a decrease in VCO2. Frequency had increased from 19 +/- 4.8 breaths/min preinfusion to 22 +/- 4.7 after 4.5 hours. After 4.5 hours, VT was still above preinfusion levels while pH and PaCO2 had decreased below them. The latter was associated with an increase in serum lactate. At no time was a decrease in tidal volume observed. Therefore, the infusion of these hormones does not simulate all the alterations observed during trauma and sepsis.

Adult↗

Breathing pattern in sarcoidosis and idiopathic pulmonary fibrosis.

We measured the volume and time components of the breathing cycle together with the P.1 in 16 sarcoidosis and 9 IPF patients. Patients in the IPF group were older, and their lung functions revealed a more restrictive pattern with small TLC, VC, and higher elastance values. We observed that in the two groups of patients there was a significant correlation between VT, f, and P.1 and lung elastance, and that the stiffer IPF patients had higher drive parameters. Hence, the main factor affecting the breathing pattern in both groups is the influence of the elastic load on the control of breathing. A significant relationship was also found between %VD/VT and elastance. We then compared the f values of the 16 sarcoidosis and 9 IPF patients with those of elastically loaded normal subjects. At equivalent levels of elastance, even though the patients and the normals showed qualitatively similar changes, the patients tended to have higher frequencies for the equivalent elastic load. In conclusion, ventilatory and drive parameters in interstitial lung diseases increased as a function of the elastic load, this load being greater in IPF than in sarcoidosis. Inflammation may stimulate the vagal receptors to increase the frequency of breathing, but this requires further study.

Female↗

Dose effect of caffeine on control of breathing and respiratory response to CO2 in cats.

The dose effect of caffeine (10-70 mg/kg iv) on pulmonary ventilation (VE), mean inspiratory flow (VT/TI), and tracheal pressure generated 0.3 and 0.5 s (P0.3 and P0.5, respectively) after the onset of inspiration against airway occluded at end expiration was studied in cats anesthetized with pentobarbital sodium (35 mg/kg ip) breathing various gas mixtures. With air and 50% O2 (balance N2), increasing doses of caffeine caused a progressive increase in VE that was associated with a reduction in end-tidal PCO2. When the latter was maintained at control (precaffeine) level by inhalation of CO2, the increase in VE was, at all caffeine levels, about three times that under nonisocapnic conditions. Both under isocapnic and nonisocapnic conditions the greatest incremental changes of VE were observed after administration of the first 10-mg/kg aliquot of caffeine, i.e., the current acceptable clinical dose. In all instances, the changes in VE were proportionally the same as the corresponding changes in VT/TI, P0.3, and P0.5, suggesting that caffeine did not appreciably alter either the shape of the inspiratory driving pressure waveform or the impedance of the respiratory system but simply acted by increasing the amplitude of the neuromuscular inspiratory output. An additive interaction between caffeine and end-tidal PCO2 was observed in the VE, VT/TI, and P0.3 responses at levels of CO2 at or below the eucapnic range.

Animals↗

Immediate response to resistive loading in anesthetized humans.

In eight spontaneously breathing anesthetized subjects (halothane: approximately 1 minimal alveolar concn; 70% N2O-30% O2), we determined 1) the inspiratory driving pressure by analysis of the pressure developed at the airway opening (Poao) during inspiratory efforts against airways occluded at end expiration; 2) the active inspiratory impedance; and 3) the immediate (first loaded breath) response to added inspiratory resistive loads (delta R). Based on these data we made model predictions of the immediate tidal volume response to delta R. Such predictions closely fitted the experimental results. The present investigation indicates that 1) in halothane-anesthetized humans the shape of the Poao wave differs from that in anesthetized animals, 2) the immediate response to delta R is not associated with appreciable changes in intensity, shape, and timing of inspiratory neural drive but depends mainly on intrinsic (nonneural) mechanisms; 3) the flow-dependent resistance of endotracheal tubes must be taken into account in studies dealing with increased neuromuscular drive in intubated subjects; and 4) in anesthetized humans Poao reflects the driving pressure available to produce the breathing movements.

Adult↗

Semistarvation and exercise.

Nutritional intake plays an important role in determining metabolic and respiratory demands during both rest and exercise. This study examines the effects in normal subjects of 4 days of semistarvation with 440 kcal/day of intravenously infused dextrose followed by the infusion of 480 kcal/day of amino acids for 48 h on the metabolic and ventilatory response to exercise (1.25, 2.50, and 5.0 kg . m/s.). After 4 days of the dextrose infusion, arterial PCO2 (P less than 0.05), and the ventilatory equivalent for CO2 (VE/VCO2, P less than 0.05) were decreased at rest compared with control measurements made prior to the dextrose infusion. During all three levels of steady-state exercise, arterial PCO2 was significantly lower (P less than 0.05) than observed before the start of the dextrose infusion. The subsequent infusion of amino acids resulted in increases in O2 consumption (V02; P less than 0.05) and minute ventilation (VE; P less than 0.05), a decrease in arterial PCO2 (P less than 0.05), and little change in CO2 production (VCO2) at rest. During low levels of exercise, compared with the values obtained following the 4 days of dextrose infusion, there were larger increases in VE and VO2, whereas VCO2 changed little. Mechanical efficiency (kcal work/kcal energy utilized) during exercise increased after 4 days of dextrose and returned to near control levels with the amino acid infusion. The adaptive response characteristic of semistarvation with dextrose appears to be altered when isocaloric amounts of amino acids are subsequently administered for short periods.

Adult↗

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↗

Active and passive respiratory mechanics in anesthetized dogs.

In six spontaneously breathing anesthetized dogs (pentobarbital sodium, 30 mg/kg) airflow, volume, and tracheal and esophageal pressures were measured. The active and passive mechanical properties of the total respiratory system, lung, and chest wall were calculated. The average passive values of respiratory system, lung, and chest wall elastances amounted to, respectively, 50.1, 32.3, and 17.7 cmH2O X l-1. Resistive pressure-vs.-flow relationships for the relaxed respiratory system, lung, and chest wall were also determined; a linear relationship was found for the former (the total passive intrinsic resistance averaged 4.1 cmH2O X l-1 X s), whereas power functions best described the others: the pulmonary pressure-flow relationship exhibited an upward concavity, which for the chest wall presented an upward convexity. The average active elastance and resistance of the respiratory system were, respectively, 64.0 cmH2O X l-1 and 5.4 cmH2O X l-1 X s. The greater active impedance reflects pressure losses due to force-length and force-velocity properties of the inspiratory muscles and those due to distortion of the respiratory system from its relaxed configuration.

Anesthesia↗

Respiratory mechanics in the adult respiratory distress syndrome.

Recent methods developed for noninvasive determination of the mechanical properties of the respiratory system have been discussed. These methods have already provided valuable information in patients mechanically ventilated in the ICU setting, and could readily be applied to ARDS. More extensive use of such methods should help to provide a better understanding of the physiologic processes and adaptive mechanisms present in both health and disease.

Airway Resistance↗

Partitioning of respiratory mechanics in halothane-anesthetized humans.

In five spontaneously breathing anesthetized subjects [halothane approximately 1 minimal alveolar concentration (MAC), 70% N2O, 30% O2], flow, changes in lung volume, and esophageal and airway opening pressure were measured in order to partition the elastance (Ers) and flow resistance (Rrs) of the total respiratory system into the lung and chest wall components. Ers averaged (+/- SD) 23.0 +/- 4.9 cmH2O X l-1, while the corresponding values of pulmonary (EL) and chest wall (EW) elastance were 14.3 +/- 3.2 and 8.7 +/- 3.0 cmH2O X l-1, respectively. Intrinsic Rrs (upper airways excluded) averaged 2.3 +/- 0.2 cmH2O X l-1 X s, the corresponding values for pulmonary (RL) and chest wall (RW) flow resistance amounting to 0.8 +/- 0.4 and 1.5 +/- 0.5 cmH2O X l-1 X s, respectively. Ers increased relative to normal values in awake state, mainly reflecting increased EL. Rw was higher than previous estimates on awake seated subjects (approximately 1.0 cmH2O X l-1 X s). RL was relatively low, reflecting the fact that the subjects had received atropine (0.3-0.6 mg) and were breathing N2O. This is the first study in which both respiratory elastic and flow-resistive properties have been partitioned into lung and chest wall components in anesthetized humans.

Adult↗

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↗

Respiratory mechanics in mechanically ventilated patients with respiratory failure.

In 11 mechanically ventilated patients, respiratory mechanics were measured 1) during constant flow inflation and 2) following end-inflation airway occlusion, as proposed in model analysis (J. Appl. Physiol. 58: 1840-1848, 1985. During the latter part of inflation, the relationship between driving pressure and lung volume change was linear, allowing determination of static respiratory elastance (Ers) and resistance (RT). The latter represents in each patient the maximum resistance value that can obtain with the prevailing time constant inhomogeneity. Following occlusion, Ers and RT were also obtained along with RT (min) which represents a minimum, i.e., resistance value that would obtain in the absence of time constant inhomogeneity. A discrepancy between inflation and occlusion Ers and RT was found only in the three patients without positive end-expiratory pressure, and could be attributed to recruitment of lung units during inflation. In all instances Ers and RT were higher than normal. RT(min) was lower in all patients than the corresponding values of RT, indicating that resistance was frequency dependent due to time constant inequalities. Changes in inflation rate did not affect Ers, while RT increased with increasing flow.

Adult↗