Mean airway pressure and mean alveolar pressure during high-frequency jet ventilation in rabbits

Mean airway pressure underestimates mean alveolar pressure during high-frequency oscillatory ventilation. We hypothesized that high inspiratory flows characteristic of high-frequency jet ventilation may generate greater inspiratory than expiratory pressure losses in the airways, thereby causing mean airway pressure to overestimate, rather than underestimate, mean alveolar pressure. To test this hypothesis, we ventilated anesthetized paralyzed rabbits with a jet ventilator at frequencies of 5, 10, and 15 Hz, constant inspiratory-to-expiratory time ratio of 0.5 and mean airway pressures of 5 and 10 cmH2O. We measured mean total airway pressure in the trachea with a modified Pitot probe, and we estimated mean alveolar pressure as the mean pressure corresponding in the static pressure-volume relationship to the mean volume of the respiratory system measured with a jacket plethysmograph. We found that mean airway pressure was similar to mean alveolar pressure at frequencies of 5 and 10 Hz but overestimated it by 1.1 and 1.4 cmH2O at mean airway pressures of 5 and 10 cmH2O, respectively, when frequency was increased to 15 Hz. We attribute this finding primarily to the combined effect of nonlinear pressure frictional losses in the airways and higher inspiratory than expiratory flows. Despite the nonlinearity of the pressure-flow relationship, inspiratory and expiratory net pressure losses decreased with respect to mean inspiratory and expiratory flows at the higher rates, suggesting rate dependence of flow distribution. Redistribution of tidal volume to a shunt airway compliance is thought to occur at high frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional differences in abdominal pressure swings in dogs

The pressure swings under the costal (Pcos) and crural diaphragms (Pcru) and between the intestinal loops (Pint) were compared with the swings in gastric pressure (Pga) in 13 supine anesthetized dogs. Pcos, Pcru, and Pint were measured with air-filled latex balloons in eight dogs and saline-filled catheters in five. Pga was measured with an air-filled balloon in all dogs. During quiet breathing differences were often present, the directions of which were variable from animal to animal. During mechanical ventilation, all pressures increased, but both Pcos and Pcru increased more than Pga, whereas only a small change was observed in Pint. During bilateral stimulation of the costal diaphragm, Pcos invariably increased more than Pga and Pint, whereas almost no change was observed in Pcru. During bilateral stimulation of the crural diaphragm, Pcru invariably increased more than Pga, Pint, and Pcos. During abdominal muscle stimulation as during external abdominal compression, Pint always increased more than Pcos and Pcru. During lower rib cage compression, Pga, Pcos, and Pcru increased more than Pint. During sternocleidomastoid stimulation, all pressure swings were negative, but the change in Pint was always smaller than in Pcos, Pcru, or Pga. Inhomogeneities observed with balloons and saline-filled catheters were similar. After the abdomen was filled with 2 liters of saline all pressure swings became much more homogeneous.     

Demonstration of airway closure in man.

After partial equilibration of the lung with a N2O gas mixture absorption of N2O by the pulmonary circulation results in a flow of gas into the lungs during breath holding. A bolus of 133Xe introduced at the mouth at the beginning of the breath hold is carried in by the gas flow and distributed according to regional perfusion. In three subjects, breath holding at FRC, apex-to-base distribution of a 133Xe bolud delivered by N2O absorption (Xecar) was similar to that of a bolus injected intravenously (Xeiv). Near RV however, much less of Xecar penetrated into dependent zones than expected from the distribution of Xeiv. In fact, distribution of Xecar did not differ from that of a slowly inhaled bolus. Correction for Compton scatter in the chest wall, measured in one subject, accounted only in part for the radioactivity recorded over dependent lung regions. The findings indicate that near RV some but not all of the dependent airways must be closed. Furthermore, the distribution of airway closure completely accounts for the distribution of a bolus inhaled from RV.     

Minimization of lung pressure swings during high-frequency ventilation: a model

The goal of this theoretical study was to develop a simple computational model for determining the lung pressure excursions that accompany the maintenance of adequate gas transport through high-frequency airway oscillations applied via the trachea (HFAO) and by transthoracic means (HFTO). Respiratory mechanics and gas transport parameters estimated from the preceding companion study (J. Appl. Physiol. 67: 985-992, 1989) were used in the model for computing tracheal, alveolar, pleural, and transpulmonary pressure swings. Comparison of model predictions with corresponding data obtained in dogs showed close agreement. The specification of eucapnia as a constraint led to results that were significantly different from previous findings which had assumed constant airflow. We used the model to identify "quasi-optimal" strategies for HFAO and HFTO application in which all pressure excursions were kept below the corresponding levels produced by conventional mechanical ventilation operating at 15 breaths/min. The model suggests the application of both HFAO and HFTO at frequencies substantially lower than the settings commonly employed in high-frequency ventilation. Application of HFAO at frequencies ranging from 1 to 4 Hz is recommended, whereas for HFTO the quasi-optimal range lies between 1 and 1.7 Hz. In patients with chronic obstructive pulmonary disease, pressure costs during HFAO or HFTO are minimized in the vicinity of 1 Hz.     

Effect of airway closure on ventilation distribution

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80-90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502-2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.     

Surfactant effects in model airway closure experiments.

The capillary instability that occurs on an annular film lining a tube is studied as a model of airway closure. Small waves in the film can amplify and form a plug across the tube. This dynamical behavior is studied using theoretical models and bench-top experiments. Our model predicts the initial growth rate of the instability and its dependence on surfactant effects. In experiments, an annular film is formed by infusion of water into an initially oil-filled glass capillary tube. The thickness of the oil film varies with the infusion flow rate. The instability growth rate and closure time are measured for a range of film thicknesses. Our theory predicts that a thinner film and higher surfactant activity enhance stability; surfactant can decrease the growth rate to 25% of its surfactant-free value. In experiments, we find that surfactant can decrease the growth rate to 20% and increase the closure time by a factor of 3.8. Functional values of a critical film thickness for closure support the theory that it increases in the presence of surfactant.     

Effects of exercise training on airway closure in asthmatics

We previously reported that responsiveness to methacholine (Mch) in the absence of deep inspiration (DI) decreased in healthy subjects after a short course of exercise training. We assessed whether a similar beneficial effect of exercise on airway responsiveness could occur in asthmatics. Nine patients (male/female: 3/6; mean age ± SD: 24 ± 2 yr) with mild untreated asthma [forced expiratory volume in 1 s (FEV(1)): 100 ± 7.4% pred; FEV(1)/vital capacity (VC): 90 ± 6.5%] underwent a series of single-dose Mch bronchoprovocations in the absence of DI in the course of a 10-wk training rowing program (6 h/wk of submaximal and maximal exercise), at baseline (week 0), and at week 5 and 10. The single-dose Mch was established as the dose able to induce ≥15% reduction in inspiratory vital capacity (IVC) and was administered to each subject at every challenge occasion. Five asthmatics (male/female: 1/4; mean age ± SD: 26 ± 3 yr) with similar baseline lung function (FEV(1): 102 ± 7.0% predicted; FEV(1)/VC: 83 ± 6.0%; P = 0.57 and P = 0.06, respectively) not participating in the exercise training program served as controls. In the trained group, the Mch-induced reduction in IVC from baseline was 22 ± 10% at week 0, 13 ± 11% at week 5 (P = 0.03), and 11 ± 8% at week 10 (P = 0.028). The Mch-induced reduction in FEV(1) did not change with exercise (P = 0.69). The reduction in responsiveness induced by exercise was of the same magnitude of that previously obtained in healthy subjects (50% with respect to pretraining). Conversely, Mch-induced reduction in IVC in controls remained unchanged after 10 wk (%reduction IVC at baseline: 21 ± 20%; after 10 wk: 29 ± 14%; P = 0.28). This study indicates that a short course of physical training is capable of reducing airway responsiveness in mild asthmatics.     

Partitioning of inspiratory pressure swings between diaphragm and intercostal/accessory muscles

We tested the hypothesis that the inspiratory pressure swings across the rib-cage pathway are the sum of transdiaphragmatic pressure (Pdi) and the pressures developed by the intercostal/accessory muscles (Pic). If correct, Pic can only contribute to lowering pleural pressure (Ppl), to the extent that it lowers abdominal pressure (Pab). To test this we measured Pab and Ppl during during Mueller maneuvers in which deltaPab = 0. Because there was no outward displacement of the rib cage, Pic must have contributed to deltaPpl, as did Pdi. Under these conditions the total pressure developed by the inspiratory muscles across the rib-cage pathway was less than Pdi + Pic. Therefore, we rejected the hypothesis. A plot of Pab vs. Ppl during relaxation allows partitioning of the diaphragmatic and intercostal/accessory muscle contributions to inspiratory pressure swings. The analysis indicates that the diaphragm can act both as a fixator, preventing transmission of Ppl to the abdomen and as an agonist. When abdominal muscles remain relaxed it only assumes the latter role to the extent that Pab increases.     

Propranolol impairs the closure of pressure ulcers in mice

Aims

β-Adrenoceptors modulate acute wound healing; however, few studies have shown the effects of β-adrenoceptor blockade on chronic wounds. Therefore, this study investigated the effect of β₁-/β₂-adrenoceptor blockade in wound healing of pressure ulcers.

Main methods

Male mice were daily treated with propranolol (β₁-/β₂-adrenoceptor antagonist) until euthanasia. One day after the beginning of treatment, two cycles of ischemia–reperfusion by external application of two magnetic plates were performed in skin to induce pressure ulcer formation.

Key findings

Propranolol administration reduced keratinocyte migration, transforming growth factor-β protein expression, re-epithelialization, and necrotic tissue loss. Neutrophil number and neutrophil elastase protein expression were increased in propranolol-treated group when compared with control group. Propranolol administration delayed macrophage mobilization and metalloproteinase-12 protein expression and reduced monocyte chemoattractant protein-1 protein expression. Myofibroblastic differentiation, angiogenesis, and wound closure were delayed in the propranolol-treated animals. Propranolol administration increased neo-epidermis thickness, reduced collagen deposition, and enhanced tenascin-C expression resulting in the formation of an immature and disorganized collagenous scar.

Significance

β₁-/β₂-Adrenoceptor blockade delays wound healing of ischemia–reperfusion skin injury through the impairment of the re-epithelialization and necrotic tissue loss which compromise wound inflammation, dermal reconstruction, and scar formation.     

Effect of previous volume history on airway closure

We studied the effect of volume history on airway closure in six healthy males ranging from 32 to 67 yr of age. The method used was to compare the regional distribution of 133Xe boluses distributed according to N2O uptake during open-glottis breath-hold maneuvers with the regional distribution of boluses of intravenously injected 133Xe. Measurements were made at two lung volumes, one close to residual volume (RV) and the other just below closing volume. The required volume was reached either by expiring from total lung capacity or by inspiring from RV. Although there was considerable airway closure in the basal regions of the lungs at both lung volumes studied, the degree of airway closure was not dependent on the previous volume history. We conclude that the airways concerned with closure have a volume-pressure hysteresis similar to that of the lung parenchyma. Furthermore in normal humans the volume-pressure hysteresis of the lung is not secondary to airway closure.