Matteo Pecchiari

Friction and lubrication of pleural tissues.

The frictional behaviour of rabbits visceral pleura sliding against parietal pleura was assessed in vitro while oscillating at physiological velocities and amplitudes under physiological normal forces. For sliding velocities up to 3 cm s(-1) and normal compressive loads up to 12 cm H2O, the average value of the coefficient of kinetic friction (mu) was constant at 0.019 +/- 0.002 (S.E.) with pleural liquid as lubricant. With Ringer-bicarbonate solution, mu was still constant, but significantly increased (Deltamu = 0.008 +/- 0.001; P < 0.001). Under these conditions, no damage of the sliding pleural surfaces was found on light and electron microscopy. Additional measurements, performed also on peritoneum, showed that changes in nominal contact area or strain of the mesothelia, temperature in the range 19-39 degrees C, and prolonged sliding did not affect mu. Gentle application of filter paper increased mu approximately 10-fold and irreversibly, suggesting alteration of the mesothelia. With packed the red blood cells (RBC) between the sliding mesothelia, mu increased appreciably but reversibly on removal of RBC suspension, whilst no ruptures of RBC occurred. In conclusion, the results indicate a low value of sliding friction in pleural tissues, partly related to the characteristics of the pleural liquid, and show that friction is independent of velocity, normal load, and nominal contact area, consistent with boundary lubrication.

Maintaining end-expiratory transpulmonary pressure prevents worsening of ventilator-induced lung injury caused by chest wall constriction in surfactant-depleted rats.

Objective:To see whether in acute lung injury 1) compression of the lungs caused by thoracoabdominal constriction degrades lung function and worsens ventilator-induced lung injury; and 2) maintaining end-expiratory transpulmonary pressure by increasing positive end-expiratory pressure reduces the deleterious effects of chest wall constriction. Design:Experimental study in rats. Setting:Physiology laboratory. Interventions:Acute lung injury was induced in three groups of nine rats by saline lavage. Nine animals immediately killed served as a control group. Group L had lavage only, group LC had the chest wall constricted with an elastic binder, and group LCP had the same chest constriction but with positive end-expiratory pressure raised to maintain end-expiratory transpulmonary pressure. After lavage, all groups were ventilated with the same pattern for 1½ hrs. Measurements and Main Results:Transpulmonary pressure, measured with an esophageal balloon catheter, lung volume changes, arterial blood gasses, and pH were assessed during mechanical ventilation. Lung wet-to-dry ratio, albumin, tumor necrosis factor-&agr;, interleukin-1&bgr;, interleukin-6, interleukin-10, and macrophage inflammatory protein-2 in serum and bronchoalveolar lavage fluid and serum E-selectin and von Willebrand Factor were measured at the end of mechanical ventilation. Lavage caused hypoxemia and acidemia, increased lung resistance and elastance, and decreased end-expiratory lung volume. With prolonged mechanical ventilation, lung mechanics, hypoxemia, and wet-to-dry ratio were significantly worse in group LC. Proinflammatory cytokines except E-selectin were elevated in serum and bronchoalveolar lavage fluid in all groups with significantly greater levels of tumor necrosis factor-&agr;, interleukin-1&bgr;, and interleukin-6 in group LC, which also exhibited significantly worse bronchiolar injury and greater heterogeneity of airspace expansion at a fixed transpulmonary pressure than other groups. Conclusions:Chest wall constriction in acute lung injury reduces lung volume, worsens hypoxemia, and increases pulmonary edema, mechanical abnormalities, proinflammatory mediator release, and histologic signs of ventilator-induced lung injury. Maintaining end-expiratory transpulmonary pressure at preconstriction levels by adding positive end-expiratory pressure prevents these deleterious effects.

Assessment of acute bronchodilator effects from specific airway resistance changes in stable COPD patients

BACKGROUND In COPD patients, reversibility is currently evaluated from the changes of forced expiratory volume at 1s (ΔFEV1) and forced vital capacity (ΔFVC). By lowering peripheral airway smooth muscle tone, bronchodilators should decrease dynamic hyperinflation, gas trapping, and possibly dyspnea at rest. Hence, we hypothesize that specific airway resistance changes (ΔsRAW) should better characterize the acute response to bronchodilators. METHODS On two days, 60 COPD patients underwent dyspnea evaluation (VAS score) and pulmonary function testing at baseline and one hour after placebo or 300μg indacaterol administration. RESULTS Spirographic and ΔsRAW-based criteria identified as responders 24 and 45 patients, respectively. ΔsRAW correlated with changes of intrathoracic gas volume (ΔITGV) (r=0.61; p<0.001), residual volume (ΔRV) (r=0.60; p<0.001), ΔFVC (r=0.44; p=0.001), and ΔVAS (r=0.73; p<0.001), while ΔFEV1 correlated only with ΔFVC (r=0.34; p=0.008). Significant differences in terms of ΔITGV (p=0.002), ΔRV (p=0.023), and ΔVAS (p<0.001) occurred only if patients were stratified according to ΔsRAW. CONCLUSIONS In assessing the acute functional effect of bronchodilators, ΔsRAW-based criterion is preferable to FEV1-FVC-based criteria, being more closely related to bronchodilator-induced improvements of lung mechanics and dyspnea at rest.

Helium-oxygen ventilation in the presence of expiratory flow-limitation: a model study.

A comparison between air and heliox (80% helium-20% oxygen) ventilation was performed using a mathematical, non-linear dynamic, morphometric model of the respiratory system. Different obstructive conditions, all causing expiratory flow limitation (EFL), were simulated during mechanical ventilation to evaluate and interpret the effects of heliox on tidal EFL and dynamic hyperinflation. Relative to air ventilation, intrinsic positive end-expiratory pressure did not change with heliox if the obstruction was limited to the peripheral airways, i.e. beyond the seventh generation. When central airways were also involved, heliox reduced dynamic hyperinflation (DH) if the flow-limiting segment remained in the fourth to seventh airway generation during the whole expiration, but produced only minor effects if, depending on the contribution of peripheral to total apparent airway resistance, the flow-limiting segment moved eventually to the peripheral airways. In no case did heliox abolish EFL occurring with air ventilation, indicating that any increase in driving pressure would be without effect on DH. Hence, to the extent that chronic obstructive pulmonary disease (COPD) affects primarily the peripheral airways, and causes EFL through the same mechanisms operating in the model, heliox administration should not be expected to appreciably reduce DH in the majority of COPD patients who are flow-limited at rest.

Effects of abdominal distension on breathing pattern and respiratory mechanics in rabbits

The effects of acute abdominal distension (AD) on the electromechanical efficiency (Eff) of the inspiratory muscles were investigated in anesthetized rabbits by recording the electrical activity (A), pressure (P) exerted by the diaphragm (di) and parasternal intercostal muscles (ic), and lung volume changes when an abdominal balloon was inflated to various degrees. Eff,ic increased with increasing AD both in supine and upright postures. In upright rabbits Eff,di increased for intermediate but decreased at higher levels of AD, whilst it decreased at all levels of AD in supine rabbits. Tidal volume (VT) response followed that of Eff,di. Tonic Aic and Adi and inspiratory prolongation were elicited by AD. The effects of these neural mechanisms, acting to limit end-expiratory lung volume and VT changes, were however small since vagotomy prevented tonic Adi and inspiratory prolongation and reduced tonic Aic, but changed lung volume responses to AD only little. Hence, reduced respiratory system compliance and changes in inspiratory muscle electromechanical efficiency dominate lung volume responses to acute AD.

Plasma membrane disruptions with different modes of injurious mechanical ventilation in normal rat lungs

Objectives:Plasma membrane disruptions are caused by excessive mechanical stress and thought to be involved in inflammatory mediator upregulation. Presently, plasma membrane disruption formation has been studied only during mechanical ventilation with large tidal volumes and limitedly to subpleural alveoli. No information is available concerning the distribution of plasma membrane disruptions within the lung or the development of plasma membrane disruptions during another modality of injurious mechanical ventilation, i.e., mechanical ventilation with eupneic tidal volume (7 mL·kg−1) at low end-expiratory lung volume. The aim of this study is to assess whether 1) mechanical ventilation with eupneic tidal volume at low end-expiratory lung volume causes plasma membrane disruptions; and 2) the distribution of plasma membrane disruptions differs from that of mechanical ventilation with large tidal volume at normal end-expiratory lung volume. Design:Experimental animal model. Subjects:Sprague-Dawley rats. Interventions:Plasma membrane disruptions have been detected as red spots in gelatin-included slices of rat lungs stained with ethidium homodimer-1 shortly after anesthesia (control) after prolonged mechanical ventilation with eupneic tidal volume at low end-expiratory lung volume followed or not by the restoration of physiological end-expiratory lung volume and after prolonged mechanical ventilation with large tidal volumes and normal end-expiratory lung volume. Measurements and Main Results:Plasma membrane disruptions increased during mechanical ventilation at low end-expiratory lung volume, mainly at the bronchiolar level. Resealing of most plasma membrane disruptions occurred on restoration of normal end-expiratory lung volume. Mechanical ventilation with large tidal volume caused the appearance of plasma membrane disruptions, both bronchiolar and parenchymal, the latter to a much greater extent than with mechanical ventilation at low end-expiratory lung volume. The increase of plasma membrane disruptions correlated with the concomitant increase of airway resistance with both modes of mechanical ventilation. Conclusions:Amount and distribution of plasma membrane disruptions between small airways and lung parenchyma depends on the type of injurious mechanical ventilation. This could be relevant to the release of inflammatory mediators.

Motor control of the diaphragm in anesthetized rabbits

Diaphragmatic regions are recruited in a specialized manner either as part of a central motor program during non-respiratory maneuvers, e.g. vomiting, or because of reflex responses, e.g. esophageal distension. Some studies in cats and dogs suggest that crural and costal diaphragm may be differentially activated also in response to respiratory stimuli from chemoreceptors or lung and chest wall mechanoreceptors. To verify whether this could occur also in other species, the EMG activity from the sternal, costoventral, costodorsal, and crural diaphragm was recorded in 42 anesthetized rabbits in response to various respiratory maneuvers, such as chemical stimulation, mechanical loading, lung volume and postural changes before and after vagotomy, or a non-respiratory maneuver such as esophageal distension. Regional activity was evaluated from timing of the raw EMG signal, and amplitude and shape of the moving average EMG. In all animals esophageal distension caused greater inhibition of the crural than sternal and costal diaphragm, whereas under all the other conditions differential diaphragmatic activation never occurred. These results indicate that in response to respiratory stimuli the rabbit diaphragm behaves as a single unit under the command of the central respiratory control system.

Bronchodilation test in COPD: effect of inspiratory manoeuvre preceding forced expiration

The effects of an inspiratory manoeuvre preceding forced expiration on functional tests performed under routine conditions before and after inhalation of a bronchodilator drug (salbutamol) were assessed on 150 consecutive chronic obstructive pulmonary disease outpatients. The patients performed forced vital capacity manoeuvres either immediately after a rapid inspiration (manoeuvre no. 1) or after a slow inspiration with a 4–6 s pause (manoeuvre no. 2). Under baseline conditions, forced expiratory volume in one second (FEV1) values were 8% (% control) larger with manoeuvre no. 1 than no. 2. FEV1 values increased with salbutamol administration by ∼8% and were, on average, still 7% larger with manoeuvre no. 1 than no. 2. The incidence of reversibility, assessed according to American Thoracic Society criteria, was 76% when manoeuvre no. 2 was selected to represent baseline conditions and manoeuvre no. 1 was chosen to represent the effects of bronchodilator administration, whereas the lowest incidence (2%) was found when manoeuvre no. 1 was selected to represent baseline conditions and manoeuvre no. 2 was chosen to represent the effects of bronchodilator administration. These results indicate that the time dependence of the forced vital capacity manoeuvre has an important impact on the assessment of routine lung function in a clinical setting and supports the notion that the time course of the inspiration preceding the forced vital capacity manoeuvre should be standardised.

Expiratory flow-limitation and heliox breathing in resting and exercising COPD patients

In 26 stable patients with chronic obstructive pulmonary disease, tidal expiratory flow-limitation (TEFL), inspiratory capacity, breathing pattern and dyspnea sensation were assessed during air and heliox (20% O(2) in He) breathing at rest and during exercise up to 2/3 maximal work rate. Breathing air, the 13 patients with TEFL at rest remained flow-limited also during exercise, while 7 of the non-flow-limited patients became flow-limited; tidal volume increased more in non-flow-limited patients, whereas inspiratory capacity decreased in flow-limited and increased in the non-flow-limited patients. Heliox did not abolish flow-limitation, had no effect on breathing pattern, reduced exercise dynamic hyperinflation in 25% of the flow-limited patients, depending on the degree of the dynamic hyperinflation on air, and lessened dyspnea sensation in all patients. Hence, the presence of TEFL has no systematic effects on the respiratory response to heliox, and the heliox-induced decrease of exercise dyspnea is not mainly due to changes in dynamic hyperinflation or TEFL.

The fall in exhaled nitric oxide with ventilation at low lung volumes in rabbits: an index of small airway injury.

The mechanisms involved in the fall of exhaled nitric oxide (NOe) concentration occurring in normal, anesthetized open chest rabbits with prolonged mechanical ventilation (MV) at low lung volume have been investigated. NOe, pH of exhaled vapor condensate, serum prostaglandin E(2), and F(2alpha), tumor necrosis factor (TNF-alpha), PaO(2), PaCO(2), pHa, and lung mechanics were assessed before, during, and after 3-4h of MV at zero end-expiratory pressure (ZEEP), with fixed tidal volume (9 ml kg(-1)) and frequency, as well as before and after 3-4h of MV on PEEP only. Lung histology and wet-to-dry ratio (W/D), and prostaglandin and TNF-alpha in bronchoalveolar lavage fluid (BALF) were also assessed. While MV on PEEP had no effect on the parameters above, MV on ZEEP caused a marked fall (45%) of NOe, with a persistent increase of airway resistance (45%) and lung elastance (12%). Changes in NOe were independent of prostaglandin and TNF-alpha levels, systemic hypoxia, hypercapnia and acidosis, bronchiolar and alveolar interstitial edema, and pH of exhaled vapor condensate. In contrast, there was a significant relationship between the decrease in NOe and bronchiolar epithelial injury score. This indicates that the fall in NOe, which occurs in the absence of an inflammatory response, is due to the epithelial damage caused by the abnormal stresses related to cyclic opening and closing of small airways with MV on ZEEP, and suggests its use as a sign of peripheral airway injury.