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PubMed1987

Effect of resting smooth muscle length on contractile response in resistance airways.

We studied the effect of resting smooth muscle length on the contractile response of the major resistance airways (generations 0-5) in 18 mongrel dogs in vivo using tantalum bronchography. Dose-response curves to 10(-10) to 10(-7) mol/kg methacholine (MCh) were generated [at functional residual capacity (FRC)] by repeated intravenous bolus administration using tantalum bronchography after each dose. Airway constriction varied substantially with dose-equivalent stimulation and varied sequentially from trachea (8.8 +/- 2.2% change in airway diam) to fifth-generation bronchus (49.8 +/- 3.0%; P less than 0.001). Length-tension curves were generated for each airway to determine the airway diameter (i.e., resting in situ smooth muscle length) at which maximal constriction was elicited using bolus intravenous injection of 10(-8) mol/kg MCh. A Frank-Starling relationship was obtained for each airway; the transpulmonary pressure at which maximal constriction was elicited increased progressively from 2.50 +/- 1.12 cmH2O for trachea (approximately FRC) to 18.3 +/- 1.05 cmH2O for fifth-generation airways (approximately 50% TLC) (P less than 0.001). A similar relationship was obtained when change in airway diameter was plotted as a function of airway radius. We demonstrate substantial heterogeneity in the lung volumes at which maximal constriction is elicited and in distribution of parasympathomimetic constriction within the first few generations of resistance bronchi. Our data also suggest that lung hyperinflation may lead to augmented airway contractile responses by shifting resting smooth muscle length toward optimum resting smooth muscle length.

Airway Resistance↗

PubMed1994

Adverse effect of hyperinflation on parasternal intercostals.

The force-generating ability of the parasternal intercostals is maintained during acute hyperinflation in the dog (Jiang et al. Am. Rev. Respir. Dis. 139: 522-528, 1989). In the present studies, we assessed whether the ability of these muscles to expand the rib cage and inflate the lungs is really maintained. We thus measured the electromyogram and the changes in length of these muscles, the axial motion of the sternum and the ribs, and the changes in pleural pressure and tidal volume in anesthetized vagotomized phrenicotomized dogs during selective parasternal stimulation and during spontaneous breathing at different lung volumes corresponding to 0, 5, 10, and 15 cmH2O positive airway pressure. Compared with functional residual capacity, parasternal stimulation at 15 cmH2O positive airway pressure caused a mild decrease in muscle shortening, a large reduction in cranial rib motion, and a large reduction in pleural pressure fall. The caudal displacement of the sternum, however, was increased. Similar alterations in rib and sternal motions and in muscle shortening were seen during spontaneous breathing; tidal volume was markedly reduced as well. These observations thus indicate that hyperinflation affects the action of the parasternal intercostals on the rib cage; their rib-elevating action is decreased, whereas their action on the sternum is increased. As a result, their ability to inflate the lung is reduced. Thus, the inflationary actions of both the diaphragm and parasternal intercostals are reduced by hyperinflation.

Animals↗

PubMed2005

Lung volumes in infants who had mild to moderate bronchopulmonary dysplasia.

"New" bronchopulmonary dysplasia (BPD) has been suggested to be a maldevelopment sequence with reduced alveolarisation of the lungs; affected infants then would be predicted to have low lung volumes. The aim of this study was to test that hypothesis by comparing the lung volumes of infants who had had mild-moderate BPD with those without BPD of similar postmenstrual age. Lung volumes of 17 infants who had mild-moderate BPD (oxygen dependent beyond 28 days, but not past term) (BPD infants) were compared to those of 17 infants without BPD (non-BPD infants). All were born at less than 33 weeks of gestation and studied at postmenstrual ages of 33 to 39 weeks. Lung volume was assessed by measurement of functional residual capacity (FRC). The BPD infants had lower lung volumes (median 19.1 ml/kg) than the non-BPD infants (median 26.5 ml/kg) (p = 0.0001). The BPD compared to the non-BPD infants were of greater postnatal age (p = 0.0003), born at a lower gestational age (p = 0.0001) and of lighter birthweight (p = 0.0001). Regression analysis, however, demonstrated that lung volume was significantly related to BPD status (p = 0.005), independently of postnatal age, birthweight and gestational age. It is concluded that the lower lung volumes of the infants who had had mild-moderate BPD support the hypothesis that new BPD is associated with poor alveolarisation.

Birth Weight↗

PubMed1987

Bronchial responsiveness to histamine in wheezy infants.

Little is known about airway responsiveness in infancy. The bronchial response to incremental doses of nebulised histamine (to a maximum dose of 8 g/l) was measured in 11 wheezy infants with a mean age of 8.7 months. The study was repeated after a 30-40 minute recovery period in seven infants and again on a separate day in 10. The index of response was the provoking concentration of histamine that produced a 30% fall in the maximum expiratory flow at functional residual capacity (PC30), taken from partial forced expiratory flow-volume curves produced in a pressure jacket. Nine of 11 infants had a PC30 of less than 8 g/l. The response was consistent between tests in both the nine responders and the two who failed to respond at 8 g/l. The PC30 was lower in infants with more severe baseline airway obstruction. Spontaneous recovery after challenge was complete in 30 minutes in seven of eight infants studied. The highest doses of histamine caused changes in the configuration of the flow-volume curves and symptomatic cough and wheeze in addition to a change in forced flow rates. This study provides clear evidence of intrathoracic airway responsiveness to histamine in infancy.

Bronchi↗

PubMed1981

Respiratory and cardiovascular responses to PEEP in artificially ventilated patients after cardiopulmonary bypass surgery.

The respiratory and haemodynamic effects of incremental levels of positive and expiratory pressure (PEEP) to 9 cm H2O were studied in ten adult patients 3--6 hours after uneventful cardiopulmonary bypass surgery. Functional residual capacity was increased and deadspace-tidal volume ratio tended to fall, the latter approaching significance at +6 and +9 cm PEEP. Thus lung volume was increased and there was a tendency to improved gas distribution to the alveoli. However there was no significant change in PaO2, alveolar-arterial oxygen tension difference or venous admixture. Cardiac index, and left ventricular strokework index were marginally depressed at 6 cm PEEP and further at 9 cm, while right atrial pressure and pulmonary artery occlusion pressure were raised at 9 cm PEEP. It would appear that low levels (3--6 cm) of PEEP do not improve gas exchange in the lungs to any worthwhile degree, and levels (6--9 cm) may impair cardiac performance.

Cardiopulmonary Bypass↗

PubMed1984

Maturation of eupneic respiration in the neonatal monkey.

Comparison between 21 2-day-old infant monkeys and 17 21-day-old infants during non-rapid eye movement sleep demonstrated that minute ventilation (VI) increased from 141 +/- 30 to 257 +/- 65 ml/min secondary to elevations in tidal volume (VT) and mean inspiratory flow (VT/Ti) with little change in respiratory timing. These volumetric parameters of ventilation as well as functional residual capacity remained significantly augmented when standardized for gain in body weight. Dynamic lung compliance increased from 0.69 +/- 0.19 to 0.89 +/- 0.39 ml/cm H2O with age while inspiratory pulmonary resistance did not change. Effective elastance fell significantly with maturation (5.27 +/- 1.51 cm H2O/ml on day 2 versus 4.15 +/- 1.35 cm H2O/ml on day 21) while effective impedance was elevated postnatally. The postnatal ventilatory gain (80% increase in VI) was attributable to increases both in dynamic lung compliance (30%) and inspiratory effort (50%) as determined by esophageal pressure changes. Isometric occlusion pressures (P0.1, P0.2 . . . Pmax) also significantly increased during this time span, suggesting that the increased ventilation resulted from an elevated respiratory drive.

Aging↗

PubMed1985

Alveolar pressures and lung volumes during high-frequency oscillatory ventilation in dogs.

A constant-volume plethysmograph was used to measure functional residual capacity (FRC) in anesthetized dogs before, during, and after high-frequency oscillatory ventilation (HFO). The phrenic nerves were electrically stimulated to provide the necessary respiratory effort. In addition to FRC, mean alveolar pressure (PA) was obtained from the pressure axis of the static pressure/volume (P/V) curve at FRC. In eight dogs, the first min of HFO at 22 ml, 20 Hz, and a 4 L/min bias flow of air increased FRC by an average of 63.6% above the apneic value, where it remained for the subsequent 15 min. PA values were significantly higher than mean airway pressures (Paw) measured in the endotracheal tube, indicating higher pressure in the terminal lung units. In five other dogs, FRC, Paw, and mean pleural pressure increased as HFO was increased from 15 to 30 Hz with 1 and 4 L/min bias flows of air. We speculate that these increases may account for both the impairment of cardiovascular function and improvements in oxygen tensions often seen with HFO.

Animals↗

PubMed1975

Static recoil of the lungs and static compliance in healthy children.

The static lung compliance was studied in 57 healthy children, 6 to 14 years old. A new method called ' end-expiratory-compliane' (C1 EE) has been developed and the results were compared to the data obtained from ZAPLETAL et al. with the 'static pressure-volume' curves technique. The advantages of the method are discussed. The static lung compliance of children increases with height. Static lung compliance value is greater than dynamic lung compliance. This difference is discussed. Static recoil pressure of the lung was measured by the oesophageal baloon technique at so-called 'zero volume' of air in the balloon. At functional residual capacity (FRC), i.e. 41-44% total lung capacity (TLC), static recoil pressure is negative in all children, according to this technique. The taller the child, the more negative is the intrathoracic pressure at the same lung volume in percent of TLC, the slopes of the P/V curve being significantly different in younger and in older children. These data are compared to those observed in adults. The elastic properties of the lungs in younger children seem to be similar to those in older adults as a result of lung growth and aging, which successively influence the elastic behaviour of the lung tissue. The influence of the experimental conditions (intra-oesophageal ballon) on the data collected in children is emphasized.

Adolescent↗

PubMed1979

Antigen-induced bronchospasm in conscious sheep.

In 10 conscious ewes with cutaneous sensitivity to Ascaris suum, measurements of pulmonary resistance (RL), static lung compliance (Cst), functional residual capacity (FRC), and arterial blood gas composition along with arterial plasma histamine concentration (H) were obtained before and after inhalation challenge with A. suum extract. Five animals showed no changes in respiratory mechanics after A. suum challenge; in these H did not change. The remaining five animals responded to A. suum challenge with bronchospasm reflected by the following maximum changes in mean values that were significant 15 and 30 min after beginning of challenge, respectively: RL 248% , FRC 126%, specific pulmonary conductance 33%, and arterial PO2 63% of base line. These parameters returned towards base line by 120 min. No changes occurred in Cst, arterial PCO2, and pH. Five minutes after beginning of A. suum challenge, mean H was increased to 423% of base line with a return to base line 10 min later. In the same 5 animals, no changes were observed in pulmonary function or H after inhalation of ragweed extract (control). These results suggest that antigen-induced bronchospasm in sensitized conscious sheep represents an anaphylactic airway response and shares distinct physiological features with human bronchial asthma including pulmonary hyperinflation.

Airway Resistance↗

PubMed1994

Respiratory mechanics of the horse during the first year of life.

This study investigated the developmental changes in the mechanical properties of the respiratory system in growing horses. Pulmonary mechanics and lung volumes were serially measured in anesthetized foals during the first year of life. Quasi-static pressure-volume curves were generated, and functional residual capacity (FRC) was measured using a closed nitrogen equilibration technique. At birth, chest wall compliance normalized to body weight was substantially less than that reported in other less precocious newborn species, while lung compliance normalized to body weight was similar to values reported for other species. Characteristics of the transition from the neonatal to adult respiratory system in the foal included a decrease in the ratios of chest wall to lung compliance (Cw/CL) and the unstressed volume of the chest wall to TLC, and a constant FRC/TLC throughout most of the study period. The somatic growth of the foal and its respiratory system were uneven processes, with increases in lung volume lagging increases in overall body size.

Age Factors↗

PubMed1995

Pre mortem analysis of lung injury and lung function in oxygen toxic rabbits.

OBJECTIVES: To determine whether respiratory system mechanics measurements could detect lung injury in oxygen toxic rabbits before clinical deterioration. To determine whether respiratory system mechanics measurements, using a power analysis, have the statistical power to detect significant reductions in hyperoxic lung injury due to an intervention when compared with traditional post mortem measurements of lung injury, extravascular lung water, and bronchoalveolar lavage protein concentration. DESIGN: Prospective, controlled study. SETTING: Institutional animal laboratories. SUBJECTS: Adult New Zealand white rabbits. INTERVENTIONS: Spontaneously breathing adult New Zealand white rabbits were exposed continuously to either > 95% oxygen or room air. MEASUREMENTS AND MAIN RESULTS: We measured arterial pH, blood gas tensions, and respiratory system mechanics in rabbits twice, both before exposure to > 95% oxygen, and after the rabbits developed symptoms of mild lung dysfunction. After the second set of respiratory system mechanics measurements, we measured extravascular lung water and bronchoalveolar lavage protein concentration in the hyperoxia-exposed rabbits and compared the values with those values obtained in animals that breathed room air only. Our hyperoxia-exposed rabbits developed symptoms of mild respiratory impairment at 69 +/- 2 hrs. In these hyperoxia-exposed rabbits, measurements of static compliance, quasi-static compliance and resistance all changed significantly (p < .05) when compared with baseline measurements. Functional residual capacity and arterial blood gas values did not change significantly. Furthermore, assuming that an intervention reduced hyperoxic lung injury by a given amount, we performed a power analysis and found that the measurement of static compliance had at least equivalent power to detect a reduction in lung injury from an intervention when compared with measurement of extravascular lung water and bronchoalveolar lavage protein concentration. CONCLUSIONS: Measurements of respiratory system mechanics can detect lung injury in hyperoxic rabbits before the onset of severe clinical deterioration or death. Furthermore, measurement of static compliance of the respiratory system is likely to be a powerful tool to detect a reduction in lung injury produced by an intervention.

Airway Resistance↗

PubMed1977

Respiratory patterns during progressive asphyxia in newborn rabbits.

During acute progressive asphyxia an abrupt transition occurs from regular respiratory efforts to primary apnea and gasping. To study this transition we measured inspiratory duration (TI), expiratory duration (TE), maximal inspiratory tracheal pressure (Pmax), electromyographic activity (EMG) of different muscle groups, and the electrocorticogram (ECoG) of 3- to 5-day-old rabbits following airway occlusion at functional residual capacity (FRC). The onset of primary apnea was associated with other central nervous system events as indicated by decerebrate posture and maximal EMG activity which were followed by relaxation, loss of EMG activity, and an isoelectric ECoG. Indices of inspiratory drive (Pmax and Pmax/TI) were preserved or accentuated following primary apnea despite a reduction of overall respiratory activity (frequency X Pmax). The onset of primary apnea appears to be due to interruption of the respiratory cycling controls rather than failure of the respiratory center which regulates inspiratory force. Gasping appears to be linked with progressive changes in respiratory patterns which are observed prior to primary apnea. These findings do not support the concept of a "gasping" center.

Airway Obstruction↗

PubMed1987

Relationship of end-expiratory pressure, lung volume, and 99mTc-DTPA clearance.

We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH2O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH2O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH2O PEEP. At 2.5 cmH2O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH2O (P less than 0.05). Between 15 and 20 cmH2O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized 99mTc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation.

Administration, Inhalation↗

PubMed2000

Airway-parenchyma uncoupling in nocturnal asthma.

Airway flow resistance is well known to be dependent upon lung volume. The rise in lung volume that occurs in asthma is therefore thought to be an important mechanism that defends airway patency. The purpose of the current study was to investigate the interdependence or mechanical coupling between airways and lung parenchyma during the inflammatory processes that occur in the patient with nocturnal asthma. Five patients with documented nocturnal asthma were studied in both a vertical and a horizontal body plethysmograph. Lung volume was altered with continuous negative pressure as applied to the chest wall with a poncho cuirass in different postures and during sleep. We found during the awake phase that an increase in lung volume decreased lower pulmonary resistance (Rlp); however, within 30 min of sleep onset, functional residual capacity (FRC) fell and Rlp rose more than would be expected for the fall in FRC. Restoring FRC to presleep values either at an early (half-hour) or a late (3-h) time point did not cause Rlp to significantly fall. A second phase of the study showed that the loss of Rlp dependence on lung volume was not due to the assumption of the supine posture. Indirect measurements of lung compliance were consistent with a stiffening of the lung. We conclude that with sleep there is an immediate uncoupling of the parenchyma to the airway, resulting in a loss of interdependence that persists throughout sleep and may contribute to the morbidity and mortality associated with nocturnal asthma.

Adult↗

PubMed1976

Pulmonary function in premature lambs during the first few hours of life.

This study establishes the mean values, variations, and trend of pulmonary function during the first few hours of life in premature lambs. Measurements of intraesophaheal and tracheal pressure, air flow, tidal volume, and functional residual capacity enabled calculations of lung compliance, specific lung compliance, and inspiratory and expiratory resistance of the lungs. Arterial carbon dioxide tension and pH were maintained within a physiologic range. Mean arterial oxygen tension (PO2) at elevated inspired oxygen tension, varied in the individual animals from 51 to 185 mm Hg at an inspired oxygen concentration of 46 to 71%. It was found that the lungs of premature lambs delivered by cesarean section were mechanically unstable; the lambs were all ineffectual at breathing and required some form of mechanical ventilation. During the first 6 hours of postnatal life the lungs of premature lambs are characterized by a wide range of mechanical values and blood gas tensions.

Animals↗

PubMed2005

Lung function at term reflects severity of bronchopulmonary dysplasia.

OBJECTIVE: To test whether infants with bronchopulmonary dysplasia (BPD) express the same functional impairments at term as healthy, preterm infants, and whether clinical severity of BPD is qualitatively or quantitatively related. STUDY DESIGN: Prospective measurements on a consecutive sample of 50 infants with BPD and 19 healthy preterm controls in a university hospital. BPD infants were classified as "severe," "moderate," or "mild," according to their need for oxygen. A multiple-breath nitrogen wash-out method was used to assess functional residual capacity (FRC) and gas mixing efficiency. Mechanical variables were estimated by the occlusion test. RESULTS: Infants with severe BPD had lower FRC, less efficient gas mixing, and higher specific conductance than those with mild and moderate BPD, and the preterm controls. Mild and moderate BPD did not differ in any property from each other but differed from controls in the same variables. The elastic properties of the respiratory system appeared unaffected by BPD. CONCLUSIONS: The ventilatory impairments in BPD were of the same nature as in healthy preterm infants when compared with term infants, but their magnitude was related to the clinical severity of the BPD. Gas mixing efficiency together with FRC appears to be useful to assess lung development in BPD.

Bronchopulmonary Dysplasia↗

PubMed1985

Influence of the heart on the vertical gradient of transpulmonary pressure in dogs.

Estimations were made of the vertical gradient of transpulmonary pressure (VGTP) from measurements of esophageal pressure in nine head-up dogs at functional residual capacity (FRC) when alive, when dead, and after total bilateral pneumothorax. The VGTP of 0.4 cmH2O/cm height in the alive state was abolished by pneumothorax, and roentgenograms showed that the heart moved in a caudal-dorsal direction. There was a small but significant increase in the VGTP on going from FRC to near total lung capacity (TLC) in alive head-up dogs. In eight dead head-up dogs heart weight was increased by replacing various amounts of heart blood with Hg. The VGTP was significantly increased from 0.28 to 0.51 cmH2O/cm height. The fractional increase in the VGTP was similar to the fractional increase in heart weight. In five dogs extrapolation to zero heart weight gave an average VGTP of 0.14 cmH2O/cm height. We conclude that the lungs help support the heart in the head-up dog and that the VGTP is in part determined by the pressure distribution required for this support.

Animals↗

PubMed1982

Mechanical properties of rat lung during prolonged hypercapnia.

Young adult rats were exposed to short-term (2 or 4 h) and prolonged (1 day to 3 wk) 5% CO2 to determine whether changes in lung mechanical properties might contribute to ventilatory adaptation. Anaesthetized rats were tracheotomized for measurement of functional residual capacity (FRC) and respiratory rates (chest intact), and for pressure-volume (PV) curves (chest open). Total lung capacity, minimal volume, lung compliance, and lung wet weight-to-dry weight ratio did not change significantly (P greater than 0.05) from air control values with CO2 exposure. From 4 h to 3 wk of hypercapnia, FRC was increased significantly (P less than 0.01) by about 25%; some of this rise could be associated with dynamic factors such as increased breathing frequency. Lung PV curves showed a small (0.5 cmH2O) left shift early in the short exposure period; this reversed into a slight (0.5 cmH2O) right shift after prolonged CO2. It is unlikely that these relatively small changes in FRC and lung recoil could contribute significantly to the previously reported long-term ventilatory adaptation to CO2.

Adaptation, Physiological↗