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Biomedical subjects

D E Leith

Publications and source records attributed to D E Leith.

At least 55 records · Page 3Linked to original sources
PubMed1984

Mass transport in mammalian lungs: comparative physiology.

Comparative physiology of mass transport of gases in mammalian lungs is surveyed in terms of the use of experimental mammals in inhalation toxicology. Principles of similarity, scaling, and the relationship of metabolism to body size are touched on, with reference to the wide variability among mammals of similar size. Mechanisms that influence the magnitude and distribution of pulmonary ventilation are reviewed, including mechanical differences associated with variation in body size. More systematic and complete descriptions and understanding are needed. Recent advances in the understanding of gas mixing and transport in airways and in the pulmonary acinus have applications in comparative physiology and inhalation toxicology that are worth exploring.

Airway Resistance↗
PubMed1984

Adrenergic blockade does not change ventilatory response to CO2 in awake resting goats.

Although adrenergic agonists increase resting ventilation and responsiveness to CO2, there are conflicting data about the effect of adrenergic blockade on ventilatory responses. In this study, we investigated the effect of alpha- or beta-adrenergic blockade on the response to hyperoxic CO2 rebreathing in awake goats. In 5 goats, studied before and after intravenous administration of phentolamine or propranolol, there was no difference (compared to control studies) in the mean slope, x-intercept, or ventilation at end-tidal PCO2 (PETCO2) = 70 torr for the CO2 response curves after either drug. When mean inspiratory flow rate (VT/Ti) was plotted against PETCO2, there was also no change in these measurements after propranolol. After phentolamine, there was a slight decrease in the slope and x-intercept, but no change in VT/Ti at PETCO2 = 70 torr. We conclude that acute administration of alpha- or beta-adrenergic blockers does not affect ventilatory response to CO2 inhalation in goats, and suggest that adrenergic activity is not an important modulating influence for CO2 responsiveness in this species.

Animals↗
PubMed1983

Maximal oxygen consumption and pulmonary diffusing capacity: a direct comparison of physiologic and morphometric measurements in canids.

The purpose of this study was to check the validity of the morphometric model for estimating physiological conductances for gases, DL. We make a direct comparison between the lung's conductance for carbon monoxide, measured physiologically using the single breath method, DLCO (sb), and that measured morphometrically using the previously published model, DLCO(mm). We also make a direct comparison between the maximum rate of oxygen uptake by the lung during exercise, VO2max, and the lung's conductance for oxygen DLO2(mm). We made these measurements on four species of canids (foxes, coyotes, dogs and wolves). We find a direct proportionality between morphometric and physiologic DLCO measurements, the morphometric being consistently larger by a factor of two. We also find that both DLCO and DLO2 increase more steeply with body mass than VO2max, the difference between the allometric slopes being the same as we had found previously in a wide range of mammalian species ranging from 2 g to 700 kg, although the slopes themselves were different. We conclude that the discordant scaling of DLO2 and VO2max with respect to body mass is not an artifact of the model for calculating DLO2 from morphometric data.

Animals↗
PubMed1983

Maximal shortening of inspiratory muscles: effect of training.

Normal subjects can increase their vital capacity by appropriate training. We tested whether that change can be achieved by greater maximal shortening of the inspiratory muscles without concomitant increases in peak static inspiratory pressures. Sixteen healthy volunteers participated in the study: eight were randomly assigned to make 20 inhalations to total lung capacity, held for 10 s with the glottis open, each day for 6 wk; the remainder served as nontraining controls. Before and after the 6-wk study period, we made multiple determinations of lung volumes and of curves relating lung volume to maximal static inspiratory (and expiratory) pressure. Control subjects had no significant changes from base line in any variable. In the training group, the mean vital capacity increased 200 +/- 74 ml (P less than 0.05) or 3.9 +/- 1.3% (P less than 0.02), without a significant change in residual volume. After training, the mean maximal inspiratory pressure at the airway opening (PI) at a lung volume equal to the base-line total lung capacity was 27 +/- 8 cmH2O in this group (vs. zero before training; P less than 0.02). Values of PI in the mid-vital capacity range did not change. We conclude that in response to appropriate training stimuli inspiratory muscles can contract to shorter minimal lengths, a capacity potentially important in progressive pulmonary hyperinflation.

Adolescent↗
PubMed1983

Acclimatization to high altitude in goats with ablated carotid bodies.

In awake goats with ablated carotid bodies, we studied resting pulmonary ventilation, CO2 production, composition of arterial blood and cerebrospinal fluid (CSF), and ventilatory responsiveness to hyperoxic CO2 rebreathing at sea level (SL) and after 3 days at simulated high altitude (HA) (PB 446 +/- 5 Torr, equivalent to 4,300 m). At HA, resting pulmonary ventilation was increased, resulting in marked hypocapnia with appropriate base deficit in blood plasma; CSF became more alkaline; CO2-response curves were shifted to lower PCO2 levels, and their slopes were steeper than at SL. Although these changes in regulation of respiration were not demonstrably different from those seen after normal acclimatization to HA with carotid bodies intact, the mechanisms of their initiation and development are probably different.

Acclimatization↗
PubMed1983

Mammalian tracheal dimensions: scaling and physiology.

Mammalian tracheal dimensions vary with body mass in a way which suggests that expiratory flow limitation, inertance, and resistance are dominant constraints on tracheal design, rather than dead space or minimum work or effort. The fraction of total resistance attributable to the trachea appears to be about the same regardless of body size. Tracheal inertance appears to vary with body mass to the -1/2 power, so that inertial pressures, like elastic and resistive pressures, are invariant with body size and natural frequency, like respiratory frequency, varies with body mass to the -1/4 power. Other dominant constraints on tracheal design may include clearance functions and specialized habitat or behavior.

Adaptation, Biological↗
PubMed1983

Reversal of arterial-to-expired CO2 partial pressure differences during rebreathing in goats.

Whether CO2 partial pressure (PCO2) in expired gas may exceed that in arterial blood has been controversial. We measured arterial PCO2 (Paco2) and end-tidal PCO2 (PETco2) in four awake goats during air breathing and during hyperoxic CO2 rebreathing in various conditions of acid-base balance. During air breathing, Paco2 was slightly higher than PETco2; i.e., the mean (+/- SE) difference, Paco2 - PETco2, was positive by + 2.36 +/- 0.53 Torr (P less than 0.001). In contrast, during CO2 rebreathing with the same techniques of measurement, this difference was always negative (mean +/- SE = -11.63 +/- 0.22 Torr, P less than 0.001), and it widened as Paco2 increased with rebreathing. Magnitude of the negative difference during rebreathing was too great to be accounted for by incorrect assumptions or measurement error, even if reasonable contributions from all known sources of error were concurrently invoked. We conclude that during hyperoxic CO2 rebreathing in goats, PETco2 exceeds Paco2.

Animals↗
PubMed1983

Target device for regulating ventilation during voluntary hyperpnea.

A ventilatory target device is described enabling subjects to maintain specified levels of ventilation during voluntary hyperpnea. Inspired air passes through a linear resistor. The associated pressure drop is measured and displayed by a mechanical manometer with a very slow response. This time-mean pressure is proportional to time-mean inspiratory flow and thus to inspired minute ventilation. Construction and calibration are described. Inspiratory resistances range between 0.6 and 1.9 cmH2O X 1(-1)S for devices with capacities up to 240 and 80 l/min, respectively. The device is simple, cheap, stable, portable, rugged, unpowered, and accurate. Inexperienced subjects quickly learn to use it and can maintain ventilations within about 5% of specified values.

Humans↗
PubMed1983

Comparative mammalian respiratory mechanics.

Respiratory mechanics can be studied in mammals of all sizes by the same methods used in man, although some definitions need to be modified and special attention given to small size and fast events. Mechanical properties vary with body size in regular ways. Operating pressures are invariant with size, volumes and compliances varying with body mass (M) approximately to the first power, and ventilation and conductance with M3/4. Thus, time constants vary with M1/4 and frequencies with M -1/4. Tracheal cross-section varies with M3/4 and appears to be constrained by expiratory flow-limitation mechanics. Smaller mammals have more compliant chest walls and lower relaxation volumes, so FRC is more likely to be influenced by reflex and dynamic mechanisms. Methods and procedures are not standardized; variability of observations is great and our ability to discriminate specialized characteristics is undeveloped. Recent fundamental challenges to conceptual foundations of scaling are unresolved. Thus, uncertainty and skepticism about existing views are appropriate.

Animals↗
PubMed1982

Dynamic hyperinflation and ventilator dependence in chronic obstructive pulmonary disease.

In advanced chronic obstructive pulmonary diseases, functional residual capacity (FRC) can be markedly increased by dynamic mechanisms involving expiratory flow limitation. We studied respiratory mechanics in a seated ventilator-dependent patient with such changes. Relaxed expiration was flow-limited; pressures of 9 to 27 cm H2O (varying with lung volume) could be applied to the airway opening (Pao) without decreasing expiratory flow rate. The FRC was at least 2 L above relaxation volume. Inspiratory total resistance was 16 cm H2O/L/s. Compliance of the lung was 0.16, chest wall was 0.04, and respiratory system was 0.032 L/cm H2O. More importantly, recoil pressures at end inspiration and end expiration, respectively, were 6.5 and 1.5 cm H2O for the lung, 33 and 11 cm H2O for chest wall, and 38 and 12 cm H2O for the respiratory system. Thus the chest wall recoiled inward at all times, pleural pressure was always substantially positive (11 to 33 cm H2O), expiratory flow was maximal, and jugular veins were always full and nonpulsating. Inspiratory work was about 0.27 kg-m per breath (7 times normal), most of it elastic work done on the chest wall.

Aged↗
PubMed1981

Potentiation by triorthotolyl phosphate of acrylate ester-induced alterations in respiration.

The purpose of this study was to determine whether triorthotolyl phosphate (TOTP), an inhibitor of carboxylesterases, would enhance the inhibitory effects of acrylate esters on respiration. Respiratory frequency was measured and the calculated decreases in respiratory frequency were used as an index of respiratory irritancy due to acrylate compounds. Tidal volume, minute ventilation, and rectal temperature were also measured. Dose-dependent decreases in frequency were found in rats inhaling methyl acrylate, ethyl acrylate and acrylic acid. Tidal volume was also reduced in rats exposed to acrylate compounds and, as a result, the percentage change in minute ventilation was greater than the percentage change in frequency or tidal volume alone. Pretreatment with TOTP (125 mg/kg) enhanced the decreases in frequency and minute ventilation caused by acrylate esters but not those resulting from exposure to acrylic acid. Exposure to ethyl acrylate and acrylic acid also resulted in dose-dependent reductions in rectal temperature. TOTP potentiated ethyl acrylate-induced decreases in rectal temperature but not those caused by acrylic acid. The results suggest that inhibition of carboxylesterases can result in enhanced irritant action of acrylate esters on the upper respiratory tract, and provide support for a local role of carboxylesterases in the detoxification of these irritant esters.

Acrylates↗
PubMed1981

Fast integrated flow plethysmograph for small mammals.

The accurate measurement of a forced vital capacity (FVC) maneuver in a small mammal requires that the plethysmograph in use have good response characteristics at high frequencies. We develop, on a theoretical basis, the behavior of zeroth-order (pressure type), first-order (flow type without inertance), and second-order (flow type with inertance) plethysmogrphs. The actual frequency response of a mouse-sized plethysmograph is then presented, and a technique for improving its response characteristics is described. A flat amplitude response (within 3% of a reference flow taken as truth) was obtained for sinusoidal inputs below 240 Hz. A phase lag with respect to the reference flow equivalent to a simple time delay of 1.4 ms was observed up to 150 Hz. A typical FVC curve for a mouse is shown, and criteria are provided for designing similar plethysmographs suitable for use with larger animals.

Animals↗
PubMed1979

Dynamic mechanisms determine functional residual capacity in mice, Mus musculus.

Awake mice (22.6--32.6 g) were anesthetized intravenously during head-out body plethysmography. One minute after pentobarbital sodium anesthesia, tidal volume had fallen from 0.28 +/- 0.04 to 0.14 +/- 0.02 ml and frequency from 181 +/- 20 to 142 +/- 8. Functional residual capacity (FRC) decreased by 0.10 +/- 0.02 ml. Expiratory flow-volume curves were linear, highly repeatable, and submaximal over substantial portions of expiration in awake and anesthetized mice; and expiration was interrupted at substantial flows that abruptly fell to and crossed zero as inspiration interrupted relaxed expiration. FRC is maintained at a higher level in awake mice due to a higher tidal volume and frequency coupled with expiratory braking (persistent inspiratory muscle activity or increased glottal resistance). In anesthetized mice, the absence of braking, coupled with reductions in tidal volume and frequency and a prolonged expiratory period, leads to FRCs that approach relaxation volume (Vr). An equation in derived to express the difference between FRC and Vr in terms of the portion of tidal volume expired without braking, the slope of the linear portion of the expiratory flow-volume curve expressed as V/V, the time fraction of one respiratory cycle spent in unbraked expiration, and respiratory frequency.

Anesthesia↗
PubMed1978

Ventilatory muscle training and the oxygen cost of sustained hyperpnea.

We measured the oxygen cost of breathing during sustained voluntary normocarbic hyperpnea in 12 subjects (4 endurance trainers, 4 strength trainers, and 4 controls) before and after a 5-wk training program limited to the ventilatory muscles (Leith, D. E., and M. E. Bradley. J. Appl. Physiol. 41: 508-516, 1976). "Steady-state" measurements of oxygen consumption were made at pulmonary ventilations ranging from 103 to 250 l/min. There were marked differences in the relationship between the metabolic cost of breathing and pulmonary ventilations between subjects. Spontaneously chosen respiratory frequencies ranged from 80 to 120 breaths/min and varied widely, even in a given subject, suggesting that the optima for frequency are broad or that optimization was imperfect. The subject group who performed endurance training increased by 19% the level of hyperpnea that they could sustain for 7--15 min, and increased their oxygen consumptions during this hyperpnea by an average of 67%. Following a 15-wk period of detraining, endurance trainers had lost 50% of their gains in the ventilations that they could sustain and in the accompanying oxygen consumptions. We conclude that ventilatory muscle endurance training can appreciably increase the aerobic endurance of the respiratory muscles.

Adult↗
PubMed1977

Relative contributions of hypocarbia and hyperpnea as mechanisms in postexercise asthma.

The purpose of this investigation was to assess the relative contributions of hyperpnea and hypocapnia in the induction of postexercise asthma. To achieve these ends, eight young asthmatics were exercised on a treadmill while minute ventilations (VE) and end-tidal CO2 (PET CO2) tensions were continuously recorded. The subjects were then restudied using a partial rebreathing technique that allowed separation of minute and alveolar ventilations so that independent evaluations could be made of the relative effects of bulk airflow on pulmonary mechanics as well as a systematic study of hypocapnia in a dose-response fashion. Sustained hyperpnea with VEidentical to those recorded during exercise was totally without effect when the mean PET CO2 was isocapnic or lowered to approximately 30 Torr. Reduction in PETCO2 to 21.3 +/-0.9 Torr brought about significant changes in mechanics, but in every variable measured, exercise produced the greatest alterations and did so at PETCO2 values that had no effect when studied in a controlled fashion. Consequently, neither high VE per se, nor hypocapnia can be considered as the mechanisms underlying exercise induced asthma.

Adult↗