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Biomedical subjects

J Milic-Emili

Publications and source records attributed to J Milic-Emili.

At least 181 records · Page 10Linked to original sources
PubMed1983

Active inspiratory impedance in halothane-anesthetized humans.

We have used the method of Siafakas et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 109-121, 1981) to determine active elastance (E'rs) and flow resistance (R'rs) of the respiratory system in eight spontaneously breathing humans anesthetized with halothane. From measurements of flow (V) and volume (V) during unoccluded inspirations and of tracheal pressure (P0tr) during subsequent inspirations with the airways occluded at end expiration, we were able to compute E'rs and R'rs as slopes and intercepts of the following function: -P0tr/V = R'rs + E'rsV/V. These measurements were repeated during inspirations loaded with a series of linear flow resistances (delta R). Neither E'rs nor R'rs was significantly affected by delta R. On the average E'rs and R'rs were, respectively, 34.4 and 16.7% higher than the corresponding passive elastance and flow resistance of the respiratory system, indicating that during active breathing the internal impedance of the respiratory system increases. This provides an internal mechanism by which passive loads are compensated.

Adult↗
PubMed1983

Active and passive respiratory mechanics and control of breathing in kittens.

In five spontaneously breathing kittens (12-13 days old), anesthetized with pentobarbital sodium, we measured the passive and active elastances and resistances of the respiratory system and the decay of inspiratory muscle pressure (PmusI) during expiration. When normalized for body weight (BW), passive resistance (Rrs . BW) was smaller in kittens than in adult cats, whereas passive elastance (Ers . BW) did not differ significantly. As a result, passive time constant (tau rs = Rrs/Ers) was shorter in kittens (mean +/- SE: 0.073 +/- 0.011 s) than in cats (0.121 +/- 0.008 s). This, associated with a faster decay in PmusI in kittens, results in 2-3 times higher flows per kilogram body weight during spontaneous tidal expirations in kittens than in cats. As in the adult cats, the average values of active elastance and resistance were higher than the passive, the average percentage increase amounting to 59 and 49%, respectively. The greater active impedance reflects force-length and force-velocity properties of inspiratory muscles. Its price is higher work of breathing; its advantage is greater intrinsic load compensation.

Airway Resistance↗
PubMed1983

Effect of ketamine on control of breathing in cats.

We studied minute ventilation, breathing pattern, end-tidal CO2 partial pressure (PACO2), and tracheal occlusion pressure in cats anesthetized with ketamine (40 and 80 mg/kg) before and after CO2 inhalation. Before CO2 administration ventilation was reduced and PACO2 increased relative to unanesthetized cats at both ketamine doses. Breathing pattern was of the "apneustic" type, being characterized by 1) prolonged inspiratory duration and relatively short expiratory time and 2) markedly curvilinear (convex upward) inspiratory volume-time profile. The latter reflected a similar curvilinearity in the tracheal occlusion pressure waveform. During CO2 inhalation, the ventilatory response to CO2 was similar to that in unanesthetized cats in spite of a depressed tracheal occlusion pressure response. This discrepancy was due to the fact that in the presence of a convex upward inspiratory volume-time profile, the shortening of inspiratory duration with increasing CO2 results in a marked increase of mean inspiratory flow, and hence the ventilatory response to CO2 remains high.

Animals↗
PubMed1983

Respiratory mechanics during halothane anesthesia and anesthesia-paralysis in humans.

In six spontaneously breathing anesthetized subjects [halothane approximately 1 maximum anesthetic concentration (MAC), 70% N2O-30% O2], we measured flow (V), volume (V), and tracheal pressure (Ptr). With airway occluded at end-inspiration tidal volume (VT), we measured Ptr when the subjects relaxed the respiratory muscles. Dividing relaxed Ptr by VT, total respiratory system elastance (Ers) was obtained. With the subject still relaxed, the occlusion was released to obtain the V-V relationship during the ensuing relaxed expiration. Under these conditions, the expiratory driving pressure is V X Ers, and thus the pressure-flow relationship of the system can be obtained. By subtracting the flow resistance of equipment, the intrinsic respiratory flow resistance (Rrs) is obtained. Similar measurements were repeated during anesthesia-paralysis (succinylcholine). Ers averaged 23.9 +/- 4 (+/- SD) during anesthesia and 21 +/- 1.8 cmH2O X 1(-1) during anesthesia-paralysis. The corresponding values of intrinsic Rrs were 1.6 +/- 0.7 and 1.9 +/- 0.9 cmH2O X 1(-1) X s, respectively. These results indicate that Ers increases substantially during anesthesia, whereas Rrs remains within the normal limits. Muscle paralysis has no significant effect on Ers and Rrs. We also provide the first measurements of inspiratory muscle activity and related negative work during spontaneous expiration in anesthetized humans. These show that 36-74% of the elastic energy stored during inspiration is wasted in terms of negative inspiratory muscle work.

Adult↗
PubMed1983

Model analysis of respiratory responses to inspiratory resistive loads.

Based on experimental inspiratory driving pressure waveforms and active respiratory impedance data of anesthetized cats, we made model predictions of the factors that determine the immediate (first loaded breath) intrinsic (i.e., nonneural) tidal volume compensation to added inspiratory resistive loads. The time course of driving pressure (P) was given by P = atb, where a is the pressure at 1 s from onset of inspiration and represents the intensity of neuromuscular drive, t is time, and b is a dimensionless index of the shape of the driving pressure wave. For a given value of active respiratory impedance, tidal volume compensation to added resistive loads increases with increasing inspiratory duration and decreasing value of b but is independent of a. Model predictions of load compensation are compared to experimental results.

Airway Resistance↗
PubMed1983

Dose effect of pentobarbital sodium on control of breathing in cats.

The dose effect of pentobarbital sodium on integrated ("moving time average") phrenic activity (EPHR), transdiaphragmatic pressure (Pdi), gastric pressure (Pga), changes in lung volume (V), and mechanical properties of the respiratory system was studied in six cats breathing room air. Increased pentobarbital dose from an initial value of 35 mg/kg ip, had no substantial effect on the relationship between EPHR and Pdi during both unoccluded and occluded inspirations, indicating that the diaphragmatic excitation-contraction coupling was not affected. Similarly, increased anesthetic dose had no effect on the relationship between EPHR and delta Pga during both occluded and unoccluded breaths, suggesting that the contribution of the diaphragm to the breathing movements did not change with increasing depth of anesthesia. Although the time course of phrenic activity showed substantial interanimal differences, the shape of the phrenic neurogram did not change substantially with increased pentobarbital dose in any of the cats studied. Increased anesthetic dose depressed, in the same proportion, the rate of rise of EPHR, Pdi, and V, but the mechanical properties of the respiratory system remained unchanged. The depression of ventilation with increased anesthetic dose was not proportional to the drop in central inspiratory activity, as quantified in terms of rate of rise of EPHR.

Airway Obstruction↗
PubMed1983

Lung mechanics in sitting and horizontal body positions.

We measured lung compliance, pulmonary flow-resistance, and expiratory reserve volume (ERV) in ten healthy young adults in sitting, supine, and lateral positions. Average lung compliance was 0.21 in sitting, 0.19 in lateral and 0.16 L.cm H2O-1 in supine positions. The change was significant (p less than 0.01) between sitting and supine position. Flow-resistance increased from 1.78 in sitting to 2.5 cm H2O.L-1.s (p less than 0.001) in lateral positions, and did not increase further in the supine posture in spite of a 35 percent decrease in ERV (p less than 0.001). Since it is known that lower airways resistance increases with decreasing lung volume, the lack of change in flow-resistance when shifting from lateral to supine posture suggests that upper airways flow-resistance (larynx and oropharynx) is greater in the lateral decubitus than in the supine positions. The decrease of lung compliance in horizontal postures probably reflects increased pulmonary blood volume and small airways closure.

Adult↗
PubMed1983

Amino acids and respiration.

Parenteral nutrition containing glucose and amino acids may stimulate respiration. To ascertain the effects of these solutions on respiration, eight normal subjects received an infusion of 5% dextrose (100 mL/h) for 7 days followed by an infusion of 3.5% amino acids (125 mL/h) for 24 hours. Minute ventilation (VE), tidal volume, mean inspiratory flow (VT/VI), oxygen consumption, and carbon dioxide production were significantly depressed after 7 days of 5% dextrose infusion. Ventilation and metabolic rate increased within 4 hours after initiation of the amino acid infusion and returned to normal 24 hours after the infusion. The effects of the amino acids on (VE) was secondary to an increase in (VT/VI), which is an indicator of neuromuscular ventilatory drive. Thus, within 4 hours amino acids will restore depressed metabolic rate, minute ventilation, and ventilatory drive after prolonged infusion of 5% dextrose.

Adult↗
PubMed1982

Pattern of reduction of ventilatory and occlusion pressure response to carbon dioxide by pentazocine in man.

Mean inspiratory flow, occlusion pressure and end-tidal PCO2 were measured in six healthy, sitting subjects, during breathing air and rebreathing carbon dioxide, before and after pentazocine 0.5 mg kg-1 i.v. and again after naloxone 20 micrograms kg-1. Pentazocine reduced the occlusion pressure and inspiratory flow responses at a given PCO2 during carbon dioxide rebreathing and these effects were antagonized by naloxone. The relationship of inspiratory flow and end-tidal carbon dioxide during rebreathing was used to measure the PCO2 value at which mean inspiratory flow was 1 litres-1. Occlusion pressure at this PCO2 was reduced in all the subjects by pentazocine, suggesting that the generation of inspiratory flow required less muscle activity. This effect was antagonized by naloxone.

Adult↗
PubMed1982

Ventilatory patterns during steady state and progressive exercise.

This study was conducted to differentiate the ventilatory and metabolic response to supine exercise at low levels (VO2 less than 1000 ml/min) from the well-documented response to high level upright exercise. Further, the respiratory cycle during exercise is analysed in terms of inspiratory time, flow and expiratory time as well as tidal volume and frequency. Using a canopy system for non-invasive measurement of breathing patterns and gas exchange, nine male subjects were studied while performing steady state (SSE) and progressive exercise (PRE). Work loads were: SSE 1-5 Kgm/sec for 17 min; PRE 1.5, 2.5, 3.75 and 5.0 Kgm/sec with 2 min increments. Total work was the same (1548 Kg . m) in both types of exercise. With SSE tidal volume (Vt) and respiratory rate (integral of) rose 70% and 30%, respectively. Minute ventilation (Ve) rose 113%. With PRE, integral of rose during the first work level, then remained stable, while Vt and Ve rose with each incremental exercise level. In both cases a decrease in expiratory time accounted for the major component of the decrease in total cycle time. With the onset of exercise, the rate of increase of inspiratory time and respiratory frequency exceeded that of tidal volume and inspiratory flow. This would suggest that these two groups of parameters are controlled by separate mechanisms, possibly, timing being under neurogenic control and flow determined by humoral factors. The respiratory quotient decreased with both forms of exercise and remained low throughout the exercise period.

Adult↗
PubMed1982

Measurement of pleural pressure in neonates.

The indirect measurement of pleural pressure in neonates is obtained from measurements of esophageal pressure (Pes) with either a liquid-filled catheter or an esophageal balloon-catheter system. The purpose of this investigation was to assess the validity of the water-filled esophageal catheter by comparing the simultaneous changes in Pes and airway opening pressure (Pao) during occluded respiratory efforts. Equal changes in Pes and Pao under this condition indicate that Pes is a valid measurement of pleural pressure. In six healthy unsedated term neonates (aged 2-3 days) we measured Pes in the lower third of the esophagus with a water-filled catheter of eight French gage (FC), which has a 2-mm internal diameter. During occlusions, changes in Pes and Pao were almost identical in magnitude and timing in each body position studied (right lateral, prone, and supine). We conclude that the water-filled 8-FG esophageal catheter gives an accurate measurement of pleural pressure changes in healthy neonates.

Catheterization↗
PubMed1982

Single-breath method for measurement of respiratory mechanics in anesthetized animals.

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg ip) airflow, changes in lung volume and tracheal pressure were measured. The airways were occluded at end inspiration (VT). During the ensuing period of apnea (Breuer-Hering inflation reflex), the animal relaxed the respiratory muscles and the passive compliance of the respiratory system (Crs) was computed by dividing VT by the tracheal pressure. While the animal was still relaxed, the airways were reopened, and during the ensuing relaxed expiration the volume-flow relationship was linear, the slope representing the time constant of the respiratory system: tau rs = Crs . Rrs, where Rrs is the flow resistance of the passive respiratory system. From the measured values of tau rs and Crs, Rrs was computed. With this information it was also possible to quantitate the antagonistic pressure developed by the inspiratory muscles during spontaneous expiration.

Airway Resistance↗
PubMed1982

Mechanical properties of the lungs during acclimatization to altitude.

Mechanical properties of the lung were studied in nine healthy lowlanders during a 6-day sojourn at an altitude of 3,457 m. In comparison to sea-level values, it was found at altitude that 1) lung volumes measured by plethysmography including total lung capacity, vital capacity, and functional residual capacity (FRC) presented small changes not exceeding 300 ml; 2) static and dynamic lung compliances were not modified but static pressure-volume curves of lungs were shifted progressively to the left (the decrease in lung elastic recoil averaged about 2 cmH2O on days 4-6); and 3) maximal midexpiratory flow, forced expiratory volume in 1 s, and maximal expiratory and inspiratory flows were increased and, conversely, airways and pulmonary flow resistances were decreased on most days at altitude. The unchanged FRC in the face of a decreased lung recoil may be explained by an increase in thoracic blood volume at altitude, but other possible mechanisms are discussed. The decrease in resistances and increase in maximal flows may be partly explained by the decreased air density at altitude, but another contributing factor such as a bronchodilatation is also suggested. It is proposed that changes in lung mechanics at altitude may account for some of the changes in the pattern of breathing and mouth occlusion pressure (P0.1) observed during acclimatization of lowlanders to altitude.

Acclimatization↗
PubMed1982

Active impedance of respiratory system in anesthetized cats.

We have assessed the validity of the method of Siafakas et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 109-121, 1981) for determining active elastance (E'rs) and flow resistance (R'rs) of the respiratory system. In six cats anesthetized with pentobarbital sodium we have measured flow, volume, and tracheal occlusion pressure during spontaneous breathing. This allowed us to compute E'rs and R'rs. From these data and the occlusion pressure wave we predicted the time course of volume during inspirations with added linear flow resistances (delta R). These were compared to the actual loaded inspirograms. The agreement was generally good, except for small predictable discrepancies with the highest delta R values, which could be attributed to decompression of thoracic gas. These results indicate that the approach of Siakafas et al. to determine E'rs and R'rs is valid. In addition, we have quantified the "terminal inhibition" of inspiratory activity, which occurs toward the end of unoccluded breaths (both loaded and unloaded).

Airway Resistance↗
PubMed1982

Effect of posture on the ventilatory response to CO2.

The effect of sitting and supine posture on breathing patterns and gas exchange during room air breathing and administration of 2 and 4% CO2 was studied in nine normal subjects using a noninvasive canopy system. During air breathing minute ventilation (VE) was 21% (P less than 0.005) higher in the sitting position. Tidal volume (VT) and mean inspiratory flow (VT/TI) were also greater in the sitting position. With the administration of 4% CO2, VE was 13.9 and 20.0 1/min in the supine and seated position, respectively. The relationship between VE and VT was the same in both cases. For any given level of VE, VT/TI was higher in the seated position. No difference in response to CO2 as measured by delta VE/delta PaCO2 and (delta VT/TI)/delta PaCO2 was observed. However, arterial PCO2 was lower both in the resting and stimulated states when sitting.

Adolescent↗
PubMed1982

Control of breathing in chronic obstructive pulmonary disease. The effect of histamine inhalation.

In 7 normocapnic and 6 hypercapnic patients with chronic obstructive pulmonary disease (COPD), we confirmed the recently reported observation that hypercapnic and/or hypoxemic patients with COPD breathe with a shorter inspiratory time (TI) and a smaller tidal volume (VT) than normocapnic and/or normoxemic patients with COPD. Both hypercapnic and normocapnic groups were exposed to doubling concentrations of aerosolized histamine, and FEV1 was measured 30 and 90 s after each 2-min exposure. A provocative concentration (PC20) of histamine was defined as that which produced a 20% decrease in FEV1. At PC20, minute ventilation and VT decreased in both groups. The decrease in VT was significantly greater in the normocapnic patients. Inspiratory flow (VT/TI) did not change in either group. Although breathing frequency (f) and inspiratory time (TI) did not change in the hypercapnic group, f increased and TI decreased significantly in the normocapnic patients. The same results were obtained when patients were separated into hypoxemic and "normoxemic" groups. At PC20, therefore, the pattern of breathing of the hypercapnic and/or hypoxemic patients showed only small variations, whereas in the normocapnic and/or "normoxemic" patients, the breathing pattern showed greater changes, becoming similar to that of the hypercapnic and/or hypoxemic patients during control breathing. We speculated, therefore, that activation of histamine-sensitive receptors in the airways could be involved in the pathophysiology of the rapid shallow breathing present at rest in hypercapnic and/or hypoxemic patients with COPD.

Aged↗
PubMed1982

Effects of airway anesthesia on pattern of breathing and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure.

To assess the role played by airway receptors in the genesis of rapid and shallow breathing of patients with chronic obstructive pulmonary disease (COPD), we studied the effects of airway anesthesia in 14 patients with COPD during acute respiratory failure. Airway anesthesia was performed by fiberoptic xylocaine administration from the larynx to the subsegmental bronchi, all patients being intubated or tracheostomized. A small decrease in minute ventilation of 6 +/- 1% of the control values occurred after airway anesthesia. This was due to a decrease (p less than 0.01) in respiratory frequency (f) (14.5 +/- 1%). The latter resulted from an increase (p less than 0.0005) in the expiratory time, whereas the inspiratory time did not change significantly. On the other hand, tidal volume increased (p less than 0.02) by 10.1 +/- 0.6%. In all patients, these modifications were accompanied by arterial blood gas deterioration, mean PaO2 and PaCO2 of 42 +/- 3 mmHg and 62 +/- 3 mmHg, respectively, 15 min after xylocaine administration, as compared with 48 +/- 2 mmHg and 54 +/- 2 mmHg, respectively, during the control period. No correlation was found between the changes in minute ventilation and PaO2 or PaCO2. We conclude that (1) activation of airway receptors are involved in the determination of the rapid and shallow breathing observed in patients with COPD during acute respiratory failure, and (2) airway xylocaine anesthesia that worsens arterial blood gases is contraindicated in these patients.

Aged↗