Effects of chest wall strapping on mechanical response to methacholine in humans.

We examined the effects of chest wall strapping (CWS) on the response to inhaled methacholine (MCh) and the effects of deep inspiration (DI). Eight subjects were studied on 1 day with MCh inhaled without CWS (CTRL), 1 day with MCh inhaled during CWS (CWSon/on), and 1 day with MCh inhaled during temporary removal of CWS (CWSoff/on). On the CWSon/on day, MCh caused greater increases in pulmonary resistance, upstream resistance, dynamic elastance, residual volume, and greater decreases in maximal expiratory flow than on the CTRL day. On the CWSoff/on day, the changes in these parameters with MCh were not different from the CTRL day. Six of the subjects were again studied using the same protocol on CTRL and CWSon/on days, except that, on a third day, MCh was given after applying the CWS, but the measurements before and after the inhalation were made without CWS (CWSon/off). The latter sequence was associated with more severe airflow obstruction than during CTRL, but less than with CWSon/on. The bronchodilator effects of a DI were blunted when CWS was applied during measurements (CWSon/on and CWSoff/on) but not after it was removed (CWSon/off). We conclude that CWS is capable of increasing airway responsiveness only when it is applied during the inhalation of the constrictor agent. We speculate that breathing at low lung volumes induced by CWS enhances airway narrowing because the airway smooth muscle is adapted at a length at which the contractile apparatus is able to generate a force greater than normal.     

Effect of shape and size of lung and chest wall on stresses in the lung.

Conflicting results have been reported on the changes in the distribution of pleural pressures caused by alterations of chest shape. To understand better the effect of shape and size of lung and chest wall on the distribution of stresses, strains, and surface pressures, we analyzed a theoretical model using the technique of finite elements. The study was in two parts. First we investigated the effects of changing the chest wall shape during expansion, and second we studied lungs of a variety of inherent shapes and sizes. We found that, in general, the distributions of alveolar size, mechanical stresses, and surface pressures in the lungs were dominated by the weight of the lung and that changing the shape of the lung or chest wall had relatively little effect. Only at high states of expansion where the lung was very stiff did changing the shape of the chest wall cause substantial changes. Altering the inherent shape of the lung generally had little effect but the topographical differences in stresses and surface pressures were approximately proportional to lung height. The results are generally consistent with those found in dog by Hoppin et al. (J. Appl. Physiol. 27: 863-873, 1969).     

An animal model for the study of regional lung function

An animal model for the study of regional lung function is described. In sheep, the bronchus to the right apical lobe (RAL) of the lung arises directly from the trachea. A tracheal divider, inserted under local anesthesia via a permanent tracheostomy, was used to separate the ventilation of the RAL from that of the rest of the lung. Lobar blood flow was estimated from the RAL contribution to the pulmonary clearance of an intravenous bolus of 85Kr. Gas exchange was measured by conventional methods. Expressed as a percentage of the value obtained for the whole lung, lobar expired volume was 14.7 +/- 4.3%, capillary perfusion was 12.3 +/- 4.2%, oxygen uptake was 14.7 +/- 4.9%, and carbon dioxide production was 13.4 +/- 5.5% (mean +/- SD of 25 studies in 11 animals breathing air). The model permits the study of experimental conditions confined to a single lobe of the lung and offers the advantages of an intact chest wall, spontaneous ventilation and an unanesthetized animal.     

Surface biophysics of the surface monolayer theory is incompatible with regional lung function.

The surface monolayer theory of Clements was tested on open surface films of calf lung surfactant extract in a leak-free vertical film surface balance in which alveolar area (A) changes in each lung zone were simulated in accordance with the theory. We found that: 1) physiologically necessary low surface tension (gamma), < 4 dyn/cm, was sustained only by continuous film compression ("expiration"); 2) compression from A equivalent to total lung capacity to functional residual capacity produced fleeting gamma reduction in all zones and quick reversal to high gamma with A changes that simulated tidal volume (VT) breathing at both 14 (adult) and 40 (neonatal) cpm; 3) phase differences between gamma and A axes of VT loops that indicate mixed surface film composition may be attributable to film inertia and viscoelasticity; 4) estimated alveolar retraction pressure due to gamma (P gamma) exceeds "net" transpulmonary pressure, i.e., favors alveolar collapse, under virtually all conditions of the theory in all zones; 5) return to transient, fleeting low gamma in successive VT cycles was determined by the inherent difference in compression and decompression rates, which results in exhaustion of available A in very few cycles; 6) the "sigh", which restores stable low gamma according to the theory, actually produced unstable high gamma during virtually all phases of the maneuver. In contrast, closed bubble films of the surfactant were structurally stable and produce stable near 0 gamma and P gamma.     

Effect of gravity on chest wall mechanics.

Chest wall mechanics was studied in four subjects on changing gravity in the craniocaudal direction (G(z)) during parabolic flights. The thorax appears very compliant at 0 G(z): its recoil changes only from -2 to 2 cmH(2)O in the volume range of 30-70% vital capacity (VC). Increasing G(z) from 0 to 1 and 1.8 G(z) progressively shifted the volume-pressure curve of the chest wall to the left and also caused a fivefold exponential decrease in compliance. For lung volume <30% VC, gravity has an inspiratory effect, but this effect is much larger going from 0 to 1 G(z) than from 1 to 1.8 G(z). For a volume from 30 to 70% VC, the effect is inspiratory going from 0 to 1 G(z) but expiratory from 1 to 1.8 G(z). For a volume greater than approximately 70% VC, gravity always has an expiratory effect. The data suggest that the chest wall does not behave as a linear system when exposed to changing gravity, as the effect depends on both chest wall volume and magnitude of G(z).     

Effects of pulse lung inflation on chest wall expiratory motor activity.

The effects of pulse lung inflation (LI) on expiratory muscle activity and phase duration (Te) were determined in anesthetized, spontaneously breathing dogs (n = 20). A volume syringe was used to inflate the lungs at various times during the expiratory phase. The magnitude of lung volume was assessed by the corresponding change in airway pressure (Paw; range 2-20 cmH(2)O). Electromyographic (EMG) activities were recorded from both thoracic and abdominal muscles. Parasternal muscle EMG was used to record inspiratory activity. Expiratory activity was assessed from the triangularis sterni (TS), internal intercostal (IIC), and transversus abdominis (TA) muscles. Lung inflations <7 cmH(2)O consistently inhibited TS activity but had variable effects on TA and IIC activity and expiratory duration. Lung inflations resulting in Paw values >7 cmH(2)O, however, inhibited expiratory EMG activity of each of the expiratory muscles and lengthened Te in all animals. The responses of expiratory EMG and Te were directly related to the magnitude of the lung inflation. The inhibition of expiratory motor activity was independent of the timing of pulse lung inflation during the expiratory phase. The inhibitory effects of lung inflation were eliminated by bilateral vagotomy and could be reproduced by electrical stimulation of the vagus nerve. We conclude that pulse lung inflation resulting in Paw between 7 and 20 cmH(2)O produces a vagally mediated inhibition of expiratory muscle activity that is directly related to the magnitude of the inflation. Lower inflation pressures produce variable effects that are muscle specific.     

Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease.

Eleven instances of a mixed acid-base disorder consisting of chronic respiratory acidosis and metabolic alkalosis were recognized in eight patients with chronic obstructive lung disease and carbon dioxide retention. Correction of the metabolic alkalosis led to substantial improvement in blood gas values and clinical symptoms. Patients with mixed chronic respiratory acidosis and metabolic alkalosis constitute a common subgroup of patients with chronic obstructive lung disease and carbon dioxide retention; these patients benefit from correction of the metabolic alkalosis.     

Effect of posture on regional gas exchange in pigs.

Although recent high-resolution studies demonstrate the importance of nongravitational determinants for both pulmonary blood flow and ventilation distributions, posture has a clear impact on whole lung gas exchange. Deterioration in arterial oxygenation with repositioning from prone to supine posture is caused by increased heterogeneity in the distribution of ventilation-to-perfusion ratios. This can result from increased heterogeneity in regional blood flow distribution, increased heterogeneity in regional ventilation distribution, decreased correlation between regional blood flow and ventilation, or some combination of the above (Wilson TA and Beck KC, J Appl Physiol 72: 2298-2304, 1992). We hypothesize that, although repositioning from prone to supine has relatively small effects on overall blood flow and ventilation distributions, regional changes are poorly correlated, resulting in regional ventilation-perfusion mismatch and reduction in alveolar oxygen tension. We report ventilation and perfusion distributions in seven anesthetized, mechanically ventilated pigs measured with aerosolized and injected microspheres. Total contributions of pulmonary structure and posture on ventilation and perfusion heterogeneities were quantified by using analysis of variance. Regional gradients of posture-mediated change in ventilation, perfusion, and calculated alveolar oxygen tension were examined in the caudocranial and ventrodorsal directions. We found that pulmonary structure was responsible for 74.0 +/- 4.7% of total ventilation heterogeneity and 63.3 +/- 4.2% of total blood flow heterogeneity. Posture-mediated redistribution was primarily oriented along the caudocranial axis for ventilation and along the ventrodorsal axis for blood flow. These mismatched changes reduced alveolar oxygen tension primarily in the dorsocaudal lung region.     

Three-dimensional characterization of regional lung deformation

The deformation of the lung during inspiration and expiration involves regional variations in volume change and orientational preferences. Studies have reported techniques for measuring the displacement field in the lung based on imaging or image registration. However, means of interpreting all the information in the displacement field in a physiologically relevant manner is lacking. We propose three indices of lung deformation that are determinable from the displacement field: the Jacobian--a measure of volume change, the anisotropic deformation index--a measure of the magnitude of directional preference in volume change and a slab-rod index--a measure of the nature of directional preference in volume change. To demonstrate the utility of these indices, they were determined for six human subjects using deformable image registration on static CT images, registered from FRC to TLC. Volume change was elevated in the inferior-dorsal region as should be expected for breathing in the supine position. The anisotropic deformation index was elevated in the inferior region owing to proximity to the diaphragm and in the lobar fissures owing to sliding. Vessel regions in the lung had a significantly rod-like deformation compared to the whole lung. Compared to upper lobes, lower lobes exhibited significantly greater volume change (19.4% and 21.3% greater in the right and left lungs on average; p<0.005) and anisotropy in deformation (26.3% and 21.8% greater in the right and left lungs on average; p<0.05) with remarkable consistency across subjects. The developed deformation indices lend themselves to exhaustive and physiologically intuitive interpretations of the displacement fields in the lung determined through image-registration techniques or finite element simulations.     

Effect of somatostatin on renal function.

Somatostatin has profound effects on both splanchnic and portal vascular beds. The effects of intravenous somatostatin (100 micrograms/h) on urinary volume, effective renal plasma flow, and glomerular filtration rate were compared with the effects of a control infusion of physiological saline in six normal subjects. Renal plasma flow and glomerular filtration rate were measured by primed constant isotope infusions of iodine-125 iodohippurate and chromium-51 edetic acid. Urinary volume, renal plasma flow, and glomerular filtration rate were measured during 20 minute clearance periods. During the control infusion urinary volume, renal plasma flow, and glomerular filtration rate remained essentially unchanged at 254 (SEM 3) ml/20 min, 568 (5) ml/min/1.73 m2, and 110 (2) ml/min/1.73 m2 respectively. From similar basal values the infusion of somatostatin led to a rapid decrease in all three variables. After 120 minutes of infusion of somatostatin urinary volume, renal plasma flow, and glomerular filtration rate were reduced to 148 (17) ml/20 min (p less than 0.01), 422 (7) ml/min/1.73 m2 (p less than 0.001), and 93 (3) ml/min/1.73 m2 (p less than 0.05) respectively. This effect on renal function should be borne in mind whenever somatostatin is used.     

Effect of coumarins on mitochondrial function.

Several derivatives of coumarin inhibited mitochondrial respiration and ATPase activity. The extent of inhibition depended on the concentration of the coumarins as well as on the substituents of the coumarin ring. Some of the coumarins stimulated ATPase activity, but all of them inhibited uncoupler-stimulated ATPase activity. Coumarins with free or substituted phenolic groups were found to exert profound effects on respiration and ATPase activity.