Production mechanism of crackles in excised normal canine lungs

Lung crackles may be produced by the opening of small airways or by the sudden expansion of alveoli. We studied the generation of crackles in excised canine lobes ventilated in an airtight box. Total airflow, transairway pressure (Pta), transpulmonary pressure (Ptp), and crackles were recorded simultaneously. Crackles were produced only during inflation and had high-peak frequencies (738 +/- 194 Hz, mean +/- SD). During inflation, crackles were produced from 111 +/- 83 ms (mean +/- SD) prior to the negative peak of Pta, presumably when small airways began to open. When end-expiratory Ptp was set constant between 15 and 20 cmH2O and end-expiratory Ptp was gradually reduced from 5 cmH2O to -15 or -20 cmH2O in a breath-by-breath manner, crackles were produced in the cycles in which end-expiratory Ptp fell below -1 to 1 cmH2O. This pressure was consistent with previously known airway closing pressures. When end-expiratory Ptp was set constant at -10 cmH2O and end inspiratory Ptp was gradually increased from -5 to 15 or 20 cmH2O, crackles were produced in inspiratory phase in which end-inspiratory Ptp exceeded 4-6 cmH2O. This pressure was consistent with previously known airway opening pressures. These results indicate that crackles in excised normal dog lungs are produced by opening of peripheral airways and are not generated by the sudden inflation of groups of alveoli.     

Postnatal development of the Hering-Breuer reflex in the rat

The intensity of the Breuer-Hering inflation reflex was studied in newborn (1 day old), in young (8 days old) and in adult rats (90 days old) under urethane general anaesthesia (1.3 g/kg i.p.). The inflation pressure was adjusted with the aid of a water-valve. The reflex was present in all 3 age groups. An inflation pressure of 0.2 kPa applied in the course of expiration produced a long lasting apnoea in newborn rats which lasted 48 normal respiratory cycles. An inflation pressure of 0.5 kPa in young rats induced an apnoea lasting for only 3 normal respiratory cycles, whereas a pressure of 1 kPa in adult rats led to an apnoea which lasted for 20 normal respiratory cycles. The compliance of the respiratory system in relation to lung weight is approximately 5 times higher in adult rats compared with that of newborn rats. It is approximately double in comparison with young rats. The pressures of inflation mentioned in the 3 age categories can be considered as equieffective from the point of stimulation pulmonary stretch receptors. It can be concluded from these findings that the reflex of Breuer-Hering in newborn rats is more potent in comparison with adult rats, but it is lower in young rats at the age of 8 days. It is suggested that the differences observed are due to functional and anatomical maturation.     

Protective and defensive airway reflexes in premature infants

The incidence of respiratory reactions to stimulation of the nasal and propharyngeal mucose was studied in 44 newborn premature infants. The inhalation of menthol fumes or the administration of drops of Mukoseptonex to the nasal mucosa caused transient respiratory arrest or a drop in the respiration rate. The heart rate rose during chemical stimulation of the nasal mucosa, possibly in association with a general arousal reaction. Mechanical stimulation of the nasal mucosal with a nylon fibre elicited an expulsive reaction in 95% of the cases. As distinct from experimental animals, sneezing was not preceded by a deep initial inspiration. Stimulation of the oropharyngeal region produced transient apnoea in 24.5% of the cases, in 18% expiratory reactions reminiscent of the expiration reflex, in 33% independent, intensive inspiratory reactions and in 24.5% cough. Cough from both the oropharyngeal and the laryngeal region had a pronounced inspiratory component. Independent inspiratory reactions may to some extent be co-responsible for the high incidence of aspirations in the neonatal period.     

Induction of anaesthesia with sevoflurane and isoflurane in the rabbit

The effects of induction of anaesthesia with sevoflurane and isoflurane were studied in rabbits. All rabbits had periods of apnoea (ranging from 30-180 s) during induction which resulted in moderate hypercapnia and acidosis. Arterial pCO2 rose from 4.1 +/- 0.3 kPa to a peak of 7.6 +/- 0.4 kPa (mean +/- SD) (both agents). All animals showed a significant reduction in heart rate (P < 0.05). Heart rate (HR) fell from 226 +/- 33 to a minimum during induction of 57 +/- 32 (sevoflurane) and 199 +/- 41 to 45 +/- 11 (isoflurane). Most animals struggled violently during induction. Use of sevoflurane did not prevent the breath-holding response seen during induction of anaesthesia with other volatile anaesthetics in this species, and the severe apnoea which occurs may represent a significant hazard. The behaviour of the animals indicated that both sevoflurane and isoflurane are aversive, suggesting that this technique should be avoided whenever possible.     

Effects of moderate hypoxia on fetal electrocortical activity, eye movements, and breathing activity in sheep

Isocapnic hypoxaemia (delta PaO2 = -8.0 +/- 0.5 mmHg; delta CaO2 = -2.86 +/- 0.20 ml/dl) was produced in fetal sheep by having the ewe breathe for one hour a gas mixture (v/v) of 10.5% O2 and 1.5% CO2 in N2. Mean fetal heart rate, blood pressure, and incidence of low voltage electrocortical activity were not affected. However, the incidence of rapid-eye-movements and breathing activity was reduced by about 40%. Breathing movements during hypoxaemia had a mean inspiratory time, breath interval, and tracheal pressure amplitude which did not differ significantly from those during control experiments in which the ewe breathed air from the plastic bag. These observations suggest that hypoxia decreases the incidence of breathing movements but does not affect the amplitude or pattern of breathing activity and that it may reduce the incidence of eye movements and breathing activity through a common mechanism.     

Role of the autonomic nervous system in the development of cardiovascular changes during nasal apnoea and lung inflation.

The role of the sympathetic system in the development of bradycardia during nasal apnoea and the role of the sympathetic and parasympathetic system in the development of cardiovascular changes during and immediately after lung inflation were determined in anaesthetized rabbits. Transection of the cervical cord (C5-7) completely blocked the hypertensive response to chemical stimulation of the nasal mucosa. The degree of nasal bradycardia was 72% lower than in stimulation of the controls. Propranolol had no effect on the hypertensive reaction, but inhibited nasal bradycardia, which was 68% lower than in the controls. Lung inflation induced tachycardia, which was only non-significantly reduced by bilateral vagotomy. Vagotomy inhibited the bradycardiac response to removal of occlusion of the trachea and the subsequent rise in blood pressure, however. Cervical cord transection likewise did not reduce inflation-induced tachycardia, but it significantly influenced the heart rate during the second phase of prolonged inflation, when the heart is affected by hypoxia. Inflation-induced tachycardia was likewise not influenced by bilateral vagotomy associated with cervical cord transection. Similar cardiac responses also occur in the presence of the simple increase in pericardial pressure produced by left pneumothorax without lung inflation.     

Factors influencing glottic dimensions during forced expiration

To examine the relationship between expiratory effort, expiratory flow, and glottic aperture, we compared the effects of actively and passively produced changes in flow in six normal subjects. During flow transients of 1.08 +/- 0.08 l/s produced by voluntary expiratory effort, glottic width (dg) increased by 54 +/- 13% (mean +/- SE). In contrast transient increases in expiratory flow, produced passively by chest compression, were not accompanied by increases in glottic dimensions. Similarly, when subjects expired through a resistance, transient passive increases in mouth pressure of 8.1 +/- 0.8 cmH2O failed to increase glottic width. However, when similar positive-pressure transients were produced actively, dg increased by 97 +/- 36% even though the expiratory efforts were accompanied by relatively small increases in flow (0.20 +/- 0.05 l/s). During tidal breathing glottic widening commenced 160 +/- 60 ms before the onset of inspiratory flow, whereas the widening associated with active flow and pressure transients did not measurably precede the onset of the change in flow or pressure. Our results indicate that transient expulsive efforts are associated with synchronous increases in dg, regardless of whether expiratory flow increases. The findings are most readily explained by a centrally determined synchronous recruitment of intrinsic laryngeal and expiratory muscles that facilitates lung emptying by minimizing airway resistance during forced exhalation.     

Health effects of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure: a systematic review of the research evidence.

OBJECTIVE: To examine the research evidence for the health consequences of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure. DESIGN: A systematic review of published research, studies being identified by searching Medline (1966-96), Embase (1974-96), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1982-95); scanning citations; and consulting experts. Studies in all languages were considered which either investigated the association between obstructive sleep apnoea in adults and key health outcomes or evaluated the effectiveness of treatment of obstructive sleep apnoea with continuous positive airways pressure in adults. MAIN OUTCOME MEASURES: Mortality, systematic hypertension, cardiac arrhythmias, ischaemic heart disease, left ventricular hypertrophy, pulmonary hypertension, stroke, vehicle accidents, measures of daytime sleepiness, and quality of life. RESULTS: 54 epidemiological studies examined the association between sleep apnoea and health related outcomes. Most were poorly designed and only weak or contradictory evidence was found of an association with cardiac arrhythmias, ischaemic heart disease, cardiac failure, systemic or pulmonary hypertension, and stroke. Evidence of a link with sleepiness and road traffic accidents was stronger but inconclusive. Only one small randomised controlled trial evaluated continuous positive airways pressure. Five non-randomised controlled trials and 38 uncontrolled trials were identified. Small changes in objectively measured daytime sleepiness were consistently found, but improvements in morbidity, mortality, and quality of life indicators were not adequately assessed. CONCLUSIONS: The relevance of sleep apnoea to public health has been exaggerated. The effectiveness of continuous positive airways pressure in improving health outcomes has been poorly evaluated. There is enough evidence suggesting benefit in reducing daytime sleepiness in some patients to warrant large randomised placebo controlled trials of continuous positive airways pressure versus an effective weight reduction programme and other interventions.     

Respiratory effects of the scalene and sternomastoid muscles in humans.

Previous studies have shown that in normal humans the change in airway opening pressure (DeltaPao) produced by all the parasternal and external intercostal muscles during a maximal contraction is approximately -18 cmH(2)O. This value is substantially less negative than DeltaPao values recorded during maximal static inspiratory efforts in subjects with complete diaphragmatic paralysis. In the present study, therefore, the respiratory effects of the two prominent inspiratory muscles of the neck, the sternomastoids and the scalenes, were evaluated by application of the Maxwell reciprocity theorem. Seven healthy subjects were placed in a computed tomographic scanner to determine the fractional changes in muscle length during inflation from functional residual capacity to total lung capacity and the masses of the muscles. Inflation induced greater shortening of the scalenes than the sternomastoids in every subject. The inspiratory mechanical advantage of the scalenes thus averaged (mean +/- SE) 3.4 +/- 0.4%/l, whereas that of the sternomastoids was 2.0 +/- 0.3%/l (P < 0.001). However, sternomastoid muscle mass was much larger than scalene muscle mass. As a result, DeltaPao generated by a maximal contraction of either muscle would be 3-4 cmH(2)O, which is about the same as DeltaPao generated by the parasternal intercostals in all interspaces.     

Respiratory and non-respiratory thoracic movements in the fetal pig.

The aim of this study was to characterize the pre-natal activity of the respiratory muscles in a non-ruminant, the pig. Tracheal pressure was recorded from 11 unanaesthetized fetal pigs in utero during late gestation in 9 sows. Two types of inspiratory effort occurred episodically in each fetus during each recording period. Episodes of breathing movements lasted 8.6 +/- 1.1 min and their overall incidence was 41.1 +/- 3.4% of recording time. The mean amplitude of the respiratory efforts was 7.6 +/- 1.1 mmHg and the mean inspiratory time was 0.8 +/- 0.1 s. Episodes of non-respiratory inspiratory efforts, considered to be fetal hiccups, lasted 5.6 +/- 0.8 min. Individual hiccups had a duration of 150-200 msec, a mean amplitude of 41.4 +/- 2.4 mmHg and a mean frequency, during episodes, of 21.9 +/- 2.0 min-1. In contrast to fetal breathing movements, hiccups appeared to be stereotyped events. It is concluded that, in common with other ruminant and non-ruminant species, two types of inspiratory effort occur in the fetal pig. Fetal hiccups, which have been observed in non-ruminant species, may be analogous to deep inspiratory efforts in the sheep fetus. The stimulus for, and function of, fetal hiccupping remain to be determined.     

Effect of fatigue on maximal inspiratory pressure-flow capacity.

The inspiratory muscles can be fatigued by repetitive contractions characterized by high force (inspiratory resistive loads) or high velocities of shortening (hyperpnea). The effects of fatigue induced by inspiratory resistive loaded breathing (pressure tasks) or by eucapnic hyperpnea (flow tasks) on maximal inspiratory pressure-flow capacity and rib cage and diaphragm strength were examined in five healthy adult subjects. Tasks consisted of sustaining an assigned breathing frequency, duty cycle, and either a "pressure-time product" of esophageal pressure (for the pressure tasks) or peak inspiratory flow rate (for the flow tasks). Esophageal pressure was measured during maximal inspiratory efforts against a closed glottis (Pesmax), maximal transdiaphragmatic pressure was measured during open-glottis expulsive maneuvers (Pdimax), and maximal inspiratory flow (VImax) was measured during maximal inspiratory efforts with no added external resistance before and after fatiguing pressure and flow tasks. The reduction in Pesmax) with pressure fatigue (-25 +/- 7%) was significantly greater than the change in Pesmax with flow fatigue (-8 +/- 8%, P less than 0.01). In contrast, the reductions in Pdimax (-11 +/- 8%) and VImax (-16 +/- 3%) with flow fatigue were greater than the changes in Pdimax (-0.6 +/- 4%, P less than 0.05) or VImax (-3 +/- 4%, P less than 0.05) with pressure fatigue. We conclude that respiratory muscle performance is dependent not only on the presence of fatigue but whether fatigue was induced by pressure tasks or flow tasks. The specific impairment of Pesmax and not of Pdimax or flow with pressure fatigue may reflect selective fatigue of the rib cage muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory arrhythmias and airway CO2, lung receptors, and central inspiratory activity

The purpose of this study was to determine whether hypocapnia affects heart rate secondary to an effect on pulmonary receptors. Dogs were anesthetized and placed on cardiopulmonary bypass. Interrelationships among airway CO2, central inspiratory activity, and lung receptor effects on respiratory-related heart rate changes (respiratory arrhythmias) were studied after vagal efferent activity was increased secondary to baroreceptor stimulation. Hypocapnia, isolated to the lungs, produced an increase in the magnitude of the respiratory arrhythmias observed. Two mechanisms may produce these results. Hypocapnia affects pulmonary receptors, which 1) reflexly alter heart rate and 2) modulate breathing frequency, thus altering the dynamics of the respiratory arrhythmias that were produced. The results also suggested that the reflex increase in heart rate in response to lung inflation and the Hering-Breuer expiratory-facilitatory reflex are either produced by different pulmonary receptors or by the same pulmonary receptors but may be mediated by different central mechanisms.     

Pulmonary edema and hemoptysis after breath-hold diving at residual volume.

To simulate pressure effects and experience thoracic compression while breath-hold diving in a relatively safe environment, competitive breath-hold divers exhale to residual volume before diving in a swimming pool, thus compressing the chest even at depth of only 3-6 m. The study was undertaken to investigate whether such diving could cause pulmonary edema and hemoptysis. Eleven volunteer breath-hold divers who regularly dive on full exhalation performed repeated dives to 6 m during a 20-min period. The subjects were studied with dynamic spirometry, video-fibernasolaryngoscopy, and single-breath diffusion capacity of carbon monoxide (Dl(CO)). The duration of dives with empty lungs ranged from 30 to 120 s. Postdiving forced vital capacity (FVC) was reduced from mean (SD) 6.57 +/- 0.88 to 6.23 +/- 1.02 liters (P < 0.05), and forced expiratory volume during the first second (FEV(1.0)) was reduced from 5.09 +/- 0.64 to 4.59 +/- 0.72 liters (P < 0.001) (n = 11). FEV(1.0)/FVC was 0.78 +/- 0.05 prediving and 0.74 +/- 0.05 postdiving (P < 0.001) (n = 11). All subjects reported a (reversible) change in their voice after diving, irritation, and slight congestion in the larynx. Fresh blood that originated from somewhere below the vocal cords was found by laryngoscopy in two subjects. Dl(CO)/alveolar ventilation (Va) was 1.56 +/- 0.17 mmol.kPa(-1).min(-1).l(-1) before diving. After diving, the Dl(CO)/Va increased to 1.72 +/- 0.24 (P = 0.001), but 20 min later it was indistinguishable from the predive value: 1.57 +/- 0.20 (n = 11). Breath-hold diving with empty lungs to shallow depths can induce hemoptysis in healthy subjects. Edema was possibly present in the lower airways, as suggested by reduced dynamic spirometry.     

Power spectra of inspiratory nerve activity with lung inflations in cats

To investigate the effect of lung inflations on the high-frequency synchrony (70-122 Hz) observed in the inspiratory activity of respiratory motor nerves of decerebrate cats, I applied a step increase in lung inflation pressure at fixed delays into the inspiratory phase and computed power spectra of phrenic neurograms before and during inflation. In 25 decerebrate paralyzed cats the frequency of the high spectral peak was 92.3 +/- 11.1 Hz before and 105.3 +/- 12.1 Hz during the step in inflation pressure, shifting upward by 13.0 +/- 6.0 Hz. For 8 of the 25 cats, the recurrent laryngeal and phrenic neurograms were recorded simultaneously. The high spectral peak was present during inspiration in the recurrent laryngeal power spectra and coherent with the high peak in the phrenic power spectra. In response to lung inflation, the high peak disappeared from the power spectra of the recurrent laryngeal nerve as the inspiratory activity was inhibited; a shift upward in frequency was not detectable. Comparing inspiratory times (TI, based on the phrenic neurograms) for breaths with no lung inflations to those for breaths with lung inflations, I found that lung inflations early in inspiration caused a decrease in TI, lung inflations at intermediates times had no effect on TI, and lung inflations late in inspiration caused an increase in TI. Despite lung inflation decreasing, not affecting, or increasing inspiratory duration and amplitude of the phrenic neurogram, lung inflation always caused a shift upward in the high-frequency peak of the phrenic power density. The fact that lung inflation, a powerful respiratory stimulus, affected the frequency of the high peak in a consistent manner suggests that the high-frequency synchrony is an important and robust feature of the central respiratory pattern generator.     

Influence of acute inspiratory loading upon diaphragm motor-evoked potentials in healthy humans.

Acute prior activity of the inspiratory muscles can enhance inspiratory muscle strength and reduce effort perception during subsequent inspiratory efforts. However, the mechanisms subserving these changes are poorly understood. Responses to magnetic stimulation in 10 subjects were studied after an acute bout of nonfatiguing inspiratory muscle loading (IML), corresponding to 40% of subjects' initial maximal inspiratory pressure (MIP), and after an acute bout of nonloaded, forced inspiration (NLF). Motor-evoked potentials elicited by cortical stimulation (MEP(c)) and by phrenic nerve stimulation (MEP(p)) were recorded transcutaneously from the diaphragm before, immediately after, and 15 min after two sets of 30 inspiratory efforts, at rest and during an MIP effort. After IML, MIP increased to 113 +/- 3% (SE) of baseline and diaphragm MEP(p) (during MIP) significantly increased (129 +/- 10% of baseline). Diaphragmatic MEP(c) (during MIP), expressed as a percentage of maximal MEP(p), decreased after IML (from 29 +/- 9% to 20 +/- 6%; P = 0.017) and after NLF (from 43 +/- 5% to 31 +/- 5%; P = 0.032). Observations from the biceps brachi demonstrated that changes after IML and NLF were specific to the inspiratory muscle, since no significant changes were observed in biceps force generation or in MEP(p) or MEP(c) amplitudes. These data indicate that after IML increased global inspiratory strength is accompanied by increased peripheral excitability and by a dampening of corticospinal excitability of the diaphragm.     

The effect of lung inflation on the inspiratory action of the canine parasternal intercostals.

Inflation induces a marked decrease in the lung-expanding ability of the diaphragm, but its effect on the parasternal intercostal muscles is uncertain. To assess this effect, the phrenic nerves and the external intercostals were severed in anesthetized, vagotomized dogs, such that the parasternal intercostals were the only muscles active during inspiration, and the endotracheal tube was occluded at different lung volumes. Although the inspiratory electromyographic activity recorded from the muscles was constant, the change in airway opening pressure decreased with inflation from -7.2+/-0.6 cmH2O at functional residual capacity to -2.2+/-0.2 cmH2O at 20-cmH2O transrespiratory pressure (P<0.001). The inspiratory cranial displacement of the ribs remained virtually unchanged, and the inspiratory caudal displacement of the sternum decreased moderately. However, the inspiratory outward rib displacement decreased markedly and continuously; at 20 cmH2O, this displacement was only 23+/-2% of the value at functional residual capacity. Calculations based on this alteration yielded substantial decreases in the change in airway opening pressure. It is concluded that, in the dog, 1) inflation affects adversely the lung-expanding actions of both the parasternal intercostals and the diaphragm; and 2) the adverse effect of inflation on the parasternal intercostals is primarily related to the alteration in the kinematics of the ribs. As a corollary, it is likely that hyperinflation also has a negative impact on the parasternal intercostals in patients with chronic obstructive pulmonary disease.     

Comparison of three tracers for detecting lung epithelial injury in anesthetized sheep

We compared the ability of three aerosolized tracers to discriminate among control, lung inflation with a positive end expired pressure of 10 cmH2O, lung vascular hypertension and edema without lung injury, and lung edema with lung injury due to intravenous oleic acid. The tracers were 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA, mol wt 492), 99mTc-human serum albumin (99mTc-ALB, mol wt 69,000), and 99mTc-aggregated albumin (99mTc-AGG ALB, mol wt 383,000). 99mTc-DTPA clearance measurements were not able to discriminate lung injury from lung inflation. The 99mTc-AGG ALB clearance rate was unchanged by lung inflation and increased slightly with lung injury. The 99mTc-ALB clearance rate (0.06 +/- 0.02%/min) was unchanged by lung inflation (0.09 +/- 0.02%/min, P greater than 0.05) or 4 h of hypertension without injury (0.09 +/- 0.04%/min, P greater than 0.05). Deposition of 99mTc-ALB within 15 min of the administration of the oleic acid increased the clearance rate to 0.19 +/- 0.06%/min, which correlated well with the postmortem lung water volume (r = 0.92, P less than 0.01). This did not occur when there was a 60-min delay in the deposition of 99mTc-ALB. We conclude that 99mTc-ALB is the best indicator for studying the effects of lung epithelial injury on protein and fluid transport into and out of the air spaces of the lungs in a minimally invasive manner.     

Inhibition of respiratory reflexes by local anesthetic aerosols in dogs and rabbits.

The effects of inhalation of 100 breaths of bupivacaine hydrochloride (5 percent solution in saline) on the cough reflex, the Breuer-Hering inflation, reflex, and the duration of apnea and bronchoconstriction produced by histamine aerosol were studied in nine anesthetized dogs. Cough was abolished in every animal; the duration of the inflation reflex was shortened from 47 +/- 4.6 s (mean plus or minus SE) to 16 +/- 3.4 s. The duration apnea produced by histamine was abolished or shortened and the rise in resistance was diminished from 170 plus or minus 22 per cent (control) to 49 +/- 6 per cent (after bupivacaine). These reflexes returned toward control values within 45 min. Bupivacaine inhibited the bronchoconstriction produced by electrical stimulation of the distal ends of cut vagus nerves both in dogs and in rabbits, but it did not alter the rise in resistance produced by histamine aerosol in vagotomized dogs. We conclude that administration of bupivacaine aerosol produces a reversible blockage of both afferent and efferent nervous activity in airways without abolishing the ability of smooth muscles to contract.     

Prolongation of inspiration during lower airway occlusion in children

Inspiration is strongly inhibited by volume-related vagal afferents in human neonates and animals, but this reflex is not as active in human adults during normal breathing. To determine whether volume-related inspiratory inhibition occurs beyond the neonatal period, we performed 10 +/- 1 end-expiratory occlusions in nine asleep children, ages 2-29 mo, with cuffed tracheostomy or endotracheal tubes in place. Airflow, tidal volume, occlusion pressure, and surface diaphragm electromyogram (DIA EMG) were simultaneously recorded. Occlusion consistently increased mechanical (P less than 0.002) and neural inspiratory times (P less than 0.001). During occluded respiratory efforts, peak amplitude of DIA EMG increased by 22 +/- 10% (P less than 0.002). In contrast, initial rate of rise of DIA EMG did not change. We conclude that in children with isolated lower airways, end-expiratory occlusions prolonged inspiratory duration as measured by both mechanical and neural parameters. The lack of an associated increase in rate of rise of DIA EMG strongly suggests that inspiration is prolonged by release of volume-related inhibition of inspiration rather than by facilitation. These data provide evidence for the presence of the Hering-Breuer reflex beyond the neonatal period.     

Effects of lung volume on clearance of solutes from the air spaces of lungs

Several investigators have shown that the clearance rate of aerosolized 99mTc-labeled diethylenetriamine pentaacetate (DTPA, mol wt = 492, radius = 0.6 nm) from the air spaces of the lungs of humans and experimental animals increases with lung volume. To further investigate this phenomenon we performed a compartmental analysis of the 2-h clearance of DTPA from the lungs of anesthetized sheep using a new method to more accurately correct for the effects of DTPA recirculation. This analysis showed that the DTPA clearance in eight sheep ventilated with zero end-expired pressure was best described by a one-compartment model with a clearance rate of 0.42 +/- 0.15%/min. Ventilating eight sheep with an end-expired pressure of 10 cmH2O throughout the study increased the end-expired volume 0.4 +/- 0.1 liter BTPS and created a clearance curve that was best described by a two-compartment model. In these sheep 56 +/- 16% of the DTPA cleared from the lungs at a rate of 7.9 +/- 2.9%/min. The remainder cleared at a rate similar to that measured in the sheep ventilated with zero end-expired pressure (0.35 +/- 0.18%/min). Additional control and lung inflation experiments were performed using 99mTc-labeled human serum albumin (mol wt = 66,000, radius = 3.6 nm). In six control sheep ventilated with zero end-expired pressure the albumin clearance was best described by a one-compartment model with a clearance rate of 0.06 +/- 0.02%/min. The clearance rate in six sheep with increased lung volume was slightly larger (0.09 +/- 0.02, P less than 0.05) but was well described by a one-compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)