Thoracoabdominal restriction in supine men: CT and lung function measurements

Thoracoabdominal restriction was brought on by means of a corset, and the subsequent effects on thoracic dimensions and lung tissue were studied by computerized tomography (CT) and by various lung function tests in supine healthy volunteers (mean age 30 yr). Restriction caused reductions in total lung capacity (helium equilibration) from mean 6.84 to 4.80 liters, in functional residual capacity (FRC) from 2.65 to 2.08 liters, and in vital capacity from 5.16 to 3.45 liters. Closing capacity (single-breath N2 washout) fell from 2.42 to 1.88 liters, thus matching the reduction in FRC. The static pressure-lung volume curve was shifted to the right by 1.5 cmH2O at 50% of total lung capacity. However, no change in the slope of the curve was observed. The diaphragm was moved cranially by 1.2 cm, and the thoracic cross-sectional area was reduced by a mean 32 cm2 at a level just above the diaphragm. No changes in the lung tissue were seen on CT scanning. Gas exchange, as assessed by multiple inert gas elimination technique and arterial blood gas analysis, was unaffected by restriction. It is concluded that in supine subjects, thoracoabdominal restriction that reduces FRC by 0.6 liter is not accompanied by atelectasis (normal CT scan). In this respect the result differs from that found in anesthetized supine subjects who show the same fall in FRC and atelectasis in dependent lung regions.     

Reproducibility of the multiple inert gas elimination technique

Although measurement errors in the multiple inert gas elimination technique have a coefficient of variation of approximately 3%, small biological fluctuations in ventilation, blood flow, or other variables must contribute additional variance to this method of assessing ventilation-perfusion (VA/Q) mismatch. To determine overall variance of computed indices of VA/Q mismatch, an analysis of variance was carried out using a total of 400 duplicate pairs of inert gas samples obtained from canine (N = 118) and human (N = 282) studies in the past 2 years. In both sets VA/Q mismatch ranged from minimal (2nd moment of ventilation and blood flow distributions, log SDV and log SDQ, respectively approximately equal to 0.3 each) to severe (log SDV and log SDQ approximately equal to 2.0). Differences between duplicate log SD values were computed and found to be a constant fraction of the mean log SD of each duplicate pair, averaging 13% for both canine and human ventilation and blood flow data. The resultant coefficient of variation for a single measurement of log SD about its mean averaged 8.6% for all data combined. This analysis demonstrates excellent reproducibility of these dispersion indices over a wide range of conditions, and if the mean of duplicate values is used, thus reducing variability by square root 2 to 6.1%, log SD can be estimated with an approximately 95% confidence limit of +/- 12%.     

Chest wall mechanics during artificial ventilation.

Chest wall mechanics were studied in six healthy volunteers before and during anesthesia prior to surgery. The intratracheal, esophageal, and intragastric pressures were measured concurrently. Gas flow was measured by pneumotachography and gas volume was obtained from it by electrical integration. Rib cage and abdomen movements were registered with magnetometers, these being calibrated by "isovolume" maneuvers. During spontaneous breathing in the conscious state, rib cage volume displacement corresponded to 40% of the tidal volume. During anesthesia and artificial ventilation, this rose to 72% of the tidal volume. The relative contributions of rib cage and abdomen displacements were not influenced by a change in tidal volume. Compliance was higher with a larger tidal volume, a finding which could be due to a curved pressure-volume relationship of the overall chest wall.     

Mutational eidence for a functional connection between two domains of 23S rRNA in translation termination

Nucleotide 1093 in domain II of Escherichia coli 23S rRNA is part of a highly conserved structure historically referred to as the GTPase center. The mutation G1093A was previously shown to cause readthrough of nonsense codons and high temperature-conditional lethality. Defects in translation termination caused by this mutation have also been demonstrated in vitro. To identify sites in 23S rRNA that may be functionally associated with the G1093 region during termination, we selected for secondary mutations in 23S rRNA that would compensate for the temperature-conditional lethality caused by G1093A. Here we report the isolation and characterization of such a secondary mutation. The mutation is a deletion of two consecutive nucleotides from helix 73 in domain V, close to the peptidyltransferase center. The deletion results in a shortening of the CGCG sequence between positions 2045 and 2048 by two nucleotides to CG. In addition to restoring viability in the presence of G1093A, this deletion dramatically decreased readthrough of UGA nonsense mutations caused by G1093A. An analysis of the amount of mutant rRNA in polysomes revealed that this decrease cannot be explained by an inability of G1093A-containing rRNA to be incorporated into polysomes. Furthermore, the deletion was found to cause UGA readthrough on its own, thereby implicating helix 73 in termination for the first time. These results also indicate the existence of a functional connection between the G1093 region and helix 73 during translation termination.     

Maintaining nitric oxide-induced airway relaxation with superoxide dismutase

BACKGROUND: We have previously shown that the protective effect of inhaled nitric oxide (iNO) against methacholine-induced bronchoconstriction is negated in airways subjected to hyperosmotic stress. In this study, hypothesizing that the impaired efficiency of iNO was caused by release of reactive oxygen radicals, we examined the effect of the radical scavenging enzyme superoxide dismutase (SOD). METHODS: Hemodynamic and respiratory measurements were performed on anesthetized rabbits after (1) inhalation of methacholine (MCh), (2) iNO (80ppm), followed by MCh, (3) inhalation of hypertonic saline (HS), followed by iNO and MCh and (4) pre-treatment with inhalation of SOD, followed by HS, iNO and MCh. We analyzed plasma for a marker of oxidative stress, 8-iso-prostaglandin (PG)F(2alpha) and for a marker of activation of COX-mediated inflammatory cascades, PGF(2alpha) metabolite. RESULTS: Pre-treatment with SOD restored the bronchoprotective response to iNO in hyperosmotic airways. No direct effect was seen by SOD treatment on levels of 8-iso-PGF(2alpha), but this marker of oxidative stress correlated positively with increased bronchoconstriction. Hyperosmotic challenge elevated levels of PGF(2alpha) metabolite, and pre-treatment with SOD protected against this activation of the inflammatory cascade. CONCLUSION: SOD pre-treatment restores the relaxant effects of iNO in hyperosmotically challenged airways by attenuating oxidative stress and activation of COX-mediated inflammatory cascades.     

Evaluation of a combination of continuum and truss finite elements in a model of passive and active muscle tissue

The numerical method of finite elements (FE) is a powerful tool for analysing stresses and strains in the human body. One area of increasing interest is the skeletal musculature. This study evaluated modelling of skeletal muscle tissue using a combination of passive non-linear, viscoelastic solid elements and active Hill-type truss elements, the super-positioned muscle finite element (SMFE). The performance of the combined materials and elements was evaluated for eccentric motions by simulating a tensile experiment from a published study on a stimulated rabbit muscle including three different strain rates. It was also evaluated for isometric and concentric contractions. The resulting stress-strain curves had the same overall pattern as the experiments, with the main limitation being sensitivity to the active force-length relation. It was concluded that the SMFE could model active and passive muscle tissue at constant rate elongations for strains below failure, as well as isometric and concentric contractions.     

Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice

Background

Deep inspirations (DI) have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation.

Methods

Balb/c mice were sensitized to ovalbumin (OVA) and exposed to nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which were given twice during the minute before assessment of lung mechanics.

Results

DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8 ± 0.3 to 2.8 ± 0.1 cmH₂O·s·mL^-1 in healthy mice and 5.1 ± 0.3 to 3.5 ± 0.3 cmH₂O·s·mL^-1 in acute airway inflammation (both P < 0.001). In healthy mice, DI reduced the maximum decrease in lung compliance from 15.9 ± 1.5% to 5.6 ± 0.6% (P < 0.0001). This protective effect was even more pronounced in mice with chronic inflammation where DI attenuated maximum decrease in compliance from 44.1 ± 6.6% to 14.3 ± 1.3% (P < 0.001). DI largely prevented increased peripheral tissue damping (G) and tissue elastance (H) in both healthy (G and H both P < 0.0001) and chronic allergen-treated animals (G and H both P < 0.0001).

Conclusion

We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.     

Effect of sedation with detomidine and butorphanol on pulmonary gas exchange in the horse

Background  

Sedation with α₂-agonists in the horse is reported to be accompanied by impairment of arterial oxygenation. The present study was undertaken to investigate pulmonary gas exchange using the Multiple Inert Gas Elimination Technique (MIGET), during sedation with the α₂-agonist detomidine alone and in combination with the opioid butorphanol.