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Biomedical subjects

D E Leith

Publications and source records attributed to D E Leith.

At least 37 records · Page 2Linked to original sources
PubMed1989

Oxygen cost of breathing during fatiguing inspiratory resistive loads.

When a subject breathes against an inspiratory resistance, the inspiratory pressure, the inspiratory flow, and the lung volume at which the breathing task takes place all interact to determine the length of time the task can be sustained (Tlim). We hypothesized that the mechanism actually limiting tasks in which these parameters were varied involved the rate of energy utilization by the inspiratory muscles. To test this hypothesis, we studied four experienced normal subjects during fatiguing breathing tasks performed over a range of pressures and flows and at two different lung volumes. We assessed energy utilization by measuring the increment in the rate of whole body O2 consumption due to the breathing task (VO2 resp). Power and mean esophageal pressure correlated with Tlim but depended also on lung volume and inspiratory flow rate. In contrast, VO2 resp closely correlated with Tlim, and this relationship was not systematically altered by inspiratory flow or lung volume. The shape of the VO2 resp vs. Tlim curve was approximately hyperbolic, with high rates of VO2 resp associated with short endurance times and lower rates of VO2 resp approaching an asymptotic value at high Tlim. These findings are consistent with a mechanism whereby a critical rate of energy utilization determines the endurance of the inspiratory pump, and that rate varies with pressure, flow, and lung volume.

Esophagus↗
PubMed1989

Adaptations to deep breath-hold diving: respiratory and circulatory mechanics.

Respiration and circulation in diving mammals are characterized by interrelated adaptations of structure, function, and behavior that are incompletely described and understood. This speculative survey touches some of them. a) Arterial blood flow can be controlled by vasoconstriction not only in arterioles but also in large arteries. The latter physiology is not well known. b) Mechanisms that might regulate and limit nitrogen uptake are not clear, although Scholander's suggestion that airspaces become gas-free during deep dives is still accepted. c) Systemic arterial retes may be able to store oxygenated blood in some diving mammals. If so, O2 in the lung might be "skimmed off" early in a dive, leaving the N2 behind. d) Variable clusters of interdependent adaptations in diving mammals include compliant chest walls that avoid thoracic squeeze; inspiratory breath holds that maintain high lung volumes; large tidal volumes that nearly empty the lung at end-expiration (so there is near-complete turnover of lung gas with each breath); airways that are "armored" by cartilage rings all the way out to the airspaces (so that they do not close and trap gas in the lung and do permit high expiratory flow rates even at very low lung volumes); submucosal vascular retes that may prevent airway squeeze; a puzzling difference in the cross-sectional areas of trachea and bony nares; and very large lungs in shallow divers (sea otters). Study of mammalian adaptations to deep diving promises to illuminate basic issues in physiology.

Adaptation, Physiological↗
PubMed1988

Increased lung volume limits endurance of inspiratory muscles.

We examined the influence of lung volume on the ability of normal subjects to sustain breathing against inspiratory resistive loading. Four normal subjects breathed on a closed circuit in which inspiration was loaded by a flow resistor. Subjects were assigned a series of breathing tasks over a range of pressures and flows. In each task there was a specified resistor and also targets for either mean esophageal or airway opening pressure, respiratory frequency, and duty cycle. Endurance was assessed as the length of time to failure of the assigned task. The prime experimental variable was lung volume, which was increased by approximately 1 liter during some tasks; 8 cmH2O continuous positive airway pressure was applied to increase lung volume without increasing elastic load. As previously shown (McCool et al.J. Appl. Physiol. 60: 299-303, 1986), for tasks that could be sustained for the same time, there was an inverse linear relationship of mean esophageal pressure with inspiratory flow rate. This trade-off of pressure and flow was apparent both with and without the increase of lung volume. Comparable tasks, however, could not be sustained as long at the higher lung volumes. This effect of volume on endurance was greater for tasks characterized by high inspiratory pressures and low flow rates than for tasks that could be sustained for the same time but that had lower inspiratory pressures and higher flow rates. This is probably due to the effects of shortening of the sarcomere on fatiguability. Increased lung volume, per se, may contribute to respiratory failure because of increased inspiratory muscle fatiguability by mechanisms independent of elastic load.

Airway Resistance↗
PubMed1988

Bracing arms increases the capacity for sustained hyperpnea.

Patients with severe chronic obstructive pulmonary disease (COPD) frequently lean forward, bracing their arms. We wondered whether the resulting shoulder girdle support improves the function of the ventilatory pump. We tested this possibility in 4 normal men by measuring the maximal ventilation that they could voluntarily sustain for 4 min while seated with their elbows braced firmly on a table and while seated with their elbows held just above the table. Bracing the arms increased ventilatory capacity significantly in all subjects, but the magnitude of the change was small (8%). We attribute the change to improved function of the accessory muscles that expand the rib cage. We speculate that this effect assumes greater importance in patients with COPD, whose diaphragms are flattened and ineffective, because such patients depend more on the inspiratory muscles of the rib cage.

Adult↗
PubMed1987

Endogenous opioids and ventilatory adaptation to prolonged hypoxia in goats.

To investigate whether endogenous opioid peptides mediate time-dependent changes in ventilatory control during prolonged hypoxia, we studied four adult goats at rest during 14 days at simulated high altitude in a hypobaric chamber (PB approximately 450 Torr). Arterial PCO2 fell during the first several hours of hypoxia, remained stable over the next 7 days, and then rose slightly (but without statistical significance) by day 14. Ventilatory responsiveness to CO2 increased during the first week of hypoxia. By day 14, while still greater than control, the ventilatory response to CO2 was less than that observed on day 7. Immunoactive beta-endorphin levels in plasma and CSF did not change during the 14-day period. Administration of naloxone on day 14 did not restore the ventilatory response to CO2 to the level observed during the first week of acclimatization. We conclude that in adult goats, time-dependent changes in ventilatory response to CO2 during acclimatization to prolonged hypoxia are not primarily attributable to alterations in endogenous opioid peptide activity.

Adaptation, Physiological↗
PubMed1987

Detection of hypercapnia by normal subjects.

1. To investigate whether changes in PaCO2 can be detected independently of the CO2-induced changes in pulmonary ventilation, we tested five normal subjects for the ability to distinguish different levels of end-tidal PCO2 (PETCO2) while holding minute ventilation constant. 2. Helped by a visual feedback system, the subjects maintained a constant ventilation targeted at a level that was higher than that dictated by the chemical drive at PETCO2 = 50 mmHg (6.7 kPa). End-tidal PCO2 was held at 40 mmHg (5.3 kPa) during the first 2 min of each test trial ('control period'); then, for 4 min ('test period'), PETCO2 was either elevated to 50 mmHg or kept at 40 mmHg. Twelve runs were performed by each subject. 3. In 24 out of the total 30 trials (80%) in which PETCO2 was raised during the test period to 50 mmHg, the subjects detected the changes. There was one false positive result (3%), when PETCO2 kept at 40 mmHg during the test period was reported as different from control. In four out of the five subjects the ability to detect the change in PETCO2 from 40 to 50 mmHg was statistically significant. 4. We conclude that increases in PETCO2 can be detected independently of changes in the absolute level of ventilation.

Carbon Dioxide↗
PubMed1987

Pliometric activity of inspiratory muscles: maximal pressure-flow curves.

We tested the hypothesis that inspiratory muscles, like other skeletal muscles, would exert greater force under pliometric conditions (being lengthened while active) than under isometric or miometric (active shortening) conditions. Maximal inspiratory pressure-flow curves of the respiratory system are analogous to the force-velocity curves for isolated muscle (Agostoni and Fenn, J. Appl. Physiol. 15:349-353, 1960). We measured esophageal pressure (Pes) and plethysmographic flow (V) at relaxation volume of the respiratory system in six trained subjects inspiring maximally through graded resistors (miometric), against a closed airway (isometric), and while constant expiratory flows were forced by a reduced pressure source at the airway opening (pliometric). Pes varied inversely with V and this trend continued into the pliometric range. In addition we found that the pressure-flow characteristics of the rib cage and of the abdomen are similar to those for the chest wall as a whole. The mechanical and energetic advantages of muscle activity under pliometric conditions may be available to some inspiratory muscles in both normal and pathological situations.

Adult↗
PubMed1987

Pathophysiology of cough.

Mucous secretions are normally removed by ciliary beating. When this defense mechanism is impaired or overwhelmed by increased secretions, cough then becomes an important means of secretion removal. For cough to be effective, the linear velocity of gas traveling through the airways should be high. Since the linear velocity of gas is related to flow and the cross-sectional area of the airways, cough is most effective when expiratory flows are great (effort independent) and dynamic compression (effort dependent) leads to a reduction of the cross-sectional area of the larger downstream airways. Cough failures may be related to either inadequate generation of expiratory flow rates (that is, in obstructive lung disease or inspiratory muscle weakness), failure to dynamically compress the airways (that is, in expiratory muscle weakness or increased collapsibility), alterations in airway geometry (that is, in bronchiectasis), or abnormal quantity or quality of mucous production (that is, in chronic bronchitis).

Cough↗
PubMed1986

Hypoproteinemic alkalosis.

Hypoproteinemia by itself causes a nonrespiratory ("metabolic") alkalosis. On the average, a decrease in plasma albumin concentration of 1 g/dl produces an increase in "standard" bicarbonate of 3.4 mM/liter, and an apparent base excess of +3.7 meq/liter; it also reduces the value of the normal anion gap by about 3 meq/liter. Concentration of plasma protein should be measured as part of the analysis of acid-base status. Interpretation of acid-base data requires special consideration in "primary hypoproteinemic alkalosis."

Adolescent↗
PubMed1986

Pressure-flow effects on endurance of inspiratory muscles.

We examined the effects of varying inspiratory pressures and flows on inspiratory muscle endurance. Four normal subjects performed voluntary forced breathing with various assigned inspiratory tasks. Duty cycle, tidal volume, and mean lung volume were the same in all tasks. Mean esophageal pressure, analogous to a pressure-time integral (PTes), was varied over a wide range. In each task the subject maintained an assigned PTes while breathing on one of a range of inspiratory resistors, and this gave a range of inspiratory flows at any given PTes. Inspiratory muscle endurance for each task was assessed by the length of time the task could be maintained (Tlim). For a given resistor, Tlim increased as PTes decreased. At a given PTes, Tlim increased as the external resistance increased and therefore as mean inspiratory flow rate (VI) decreased. Furthermore, for a given Tlim, PTes and VI were linearly related with a negative slope. We conclude that inspiratory flow, probably because of its relationship to the velocity of muscle shortening, is an independent variable importantly influencing endurance of the inspiratory muscles.

Adult↗
PubMed1986

Mean airway opening pressure as an index of inspiratory muscle task intensity.

The relationship between mean values of pressure (pressure-time integral including both inspiration and expiration) measured at the airway opening (Pao) and in the esophagus (Pes) is described for ventilation on a variety of external inspiratory resistances. Pao/Pes was 0.85 or greater when the external inspiratory resistance was a 4.0-mm or smaller endotracheal tube adaptor. Additionally, Pao can be easily and accurately measured by a slowly responding mechanical manometer. This device is simple in design, unpowered, inexpensive, and can be used outside the laboratory as part of an inspiratory muscle training program.

Esophagus↗
PubMed1985

Tracheal insufflation of O2 (TRIO) at low flow rates sustains life for several hours.

The emergency management of respiratory arrest can be a difficult problem. The authors hypothesized that tracheal insufflation of O2 (TRIO) at low flows could provide adequate oxygenation and sufficient CO2 elimination to sustain life until more definitive (but more difficult to implement) measures could be applied. Therefore, 10 anesthetized, paralyzed dogs (15.9-48.2 kg), initially ventilated with conventional mechanical ventilation (CMV) using room air, were studied. CMV was stopped and a 1- or 5-mm id catheter with a constant flow (V) of O2 ranging from 0.2 to 3.0 l/min was inserted to within 1 cm of the carina. With all flow rates, PaO2 and PaCO2 initially increased with time; the rate of increase of PaO2 was greater and that of PaCO2 was less, with increasing V. In three dogs studied at flow rates of 2.0 or 3.0 l/min, arterial blood gases reached a plateau after about 2 h: pH = 6.87; PCO2 = 164 mmHg; and PO2 = 363 mmHg (mean values). These studies were stopped at between 4 and 5 h, with no dogs showing any signs of cardiovascular or other decompensation. Results in which catheter position was studied indicated that as long as the catheter tip was at or past the carina, gas transport was similar to that observed when the catheter tip was 1 cm proximal to the carina. The authors conclude that TRIO at low flow rates can produce sufficient gas exchange to support life for prolonged periods in apneic dogs.

Animals↗
PubMed1985

Endogenous opioids and ventilatory responses to hypercapnia in normal humans.

Though administration of opioid peptides depresses ventilation and ventilatory responsiveness, the role of endogenous opioid peptides in modulating ventilatory responsiveness is not clear. We studied the interaction of endogenous opioids and ventilatory responses in 12 adult male volunteers by relating hypercapnic responsiveness to plasma levels of immunoactive beta-endorphin and by administering the opiate antagonist naloxone. Ventilatory responsiveness to hypercapnia was not altered by pretreatment with naloxone, and this by itself suggests that endogenous opioids have no role in modulating this response. However, there was an inverse relationship between basal levels of immunoactive beta-endorphin in plasma and ventilatory responsiveness to CO2. Furthermore, plasma beta-endorphin levels rose after short-term hypercapnia but only when subjects had been pretreated with naloxone. We conclude that measurement of plasma endorphin levels suggests relationships between endogenous opioid peptides and ventilatory responses to CO2 that are not apparent in studies limited to assessing the effect of naloxone.

Adult↗
PubMed1985

Endogenous opioids and ventilatory responses to hypoxia in normal humans.

We studied the putative role of endorphins in modulating hypoxic ventilatory responsiveness. In 12 healthy men, minute ventilation (VE)and mouth occlusion pressure (P0.1) responses to progressive isocapnic hypoxia were determined before and after the intravenous administration of the opioid antagonist naloxone (10 mg) or placebo. Plasma levels of beta-endorphin were measured before and after hypoxia. Naloxone did not affect the slopes or x-intercepts of the relationships between either VE or P0.1 and arterial O2 saturation. There was no correlation between the baseline plasma level of beta-endorphin and any measure of responsiveness to hypoxia. Plasma beta-endorphin levels were not affected by either short-term hypoxia or naloxone alone; however, when hypoxia followed naloxone administration, mean +/- SD beta-endorphin increased from 8.0 +/- 8.9 pg/ml to 20.2 +/- 16.6 pg/ml (p less than 0.005). We concluded that endogenous opioids do not have an important modulating influence on hypoxic ventilatory responsiveness in adult human volunteers.

Adult↗
PubMed1985

The development of cough.

Control of coughing is immature at birth; less than half of newborns cough spontaneously or on direct laryngeal stimulation. It is not known whether timing and distribution of motor outflow is optimized for muscle and lung mechanics. The musculoskeletal system is immature. Inspiratory and expiratory pressures appear to be adequate at birth, but the ranges of pressures and volumes actually used by infants during coughing are not well known. Lung structure is immature at birth. Low lung recoil pressures and low tracheal elastance (easy collapsibility) probably combine to reduce maximal gas velocities in uncompressed intrathoracic airways, and relatively low maximal expiratory pressures and high flow-resistive losses may combine to reduce maximal velocities in compressed regions of intrathoracic airways. Better descriptions of normal and pathologic aspects of structure and function are needed, with attention to control, motor, and lung mechanical functions during coughing and forced expiration in human infants. Application to the developing respiratory system of scaling techniques and models of forced expiration, and advances in understanding of two-phase flow in airways, would be helpful.

Cough↗
PubMed1984

Naloxone does not affect ventilatory responses to hypoxia and hypercapnia in rats.

Ventilatory responses (tidal volume, respiratory frequency, and minute ventilation) to steady-state hypoxia and steady-state hypercapnia were measured plethysmographically in awake unrestrained adult rats, before and after subcutaneous injection of placebo (saline) naloxone in doses up to 5.0 mg/kg. Naloxone did not alter the ventilatory responses to hypoxia or hypercapnia.

Animals↗
PubMed1984

Respiration of chemodenervated goats in acute metabolic acidosis.

In awake goats before and after ablation of carotid bodies (CBx) we studied the effect of acute metabolic acidosis (AMA) produced by intravenous infusion of HCl on composition of arterial blood and CSF, and on ventilatory responsiveness to hyperoxic CO2 rebreathing AMA caused decrease in PaCO2 (breathing air at rest) indicating that alveolar ventilation was increased relative to CO2 production; position of CO2 response curves was shifted toward lower values of PCO2. These changes were similar before and after CBx, though the levels of PCO2 in arterial blood during air breathing at rest, and in expired gas at a given level of ventilation during CO2 rebreathing, were higher after CBx. We conclude that a respiratory adaptation to AMA does occur in goats deprived of peripheral chemoreceptors, and is probably mediated by the central chemoreceptors.

Acidosis↗