Edgardo D’Angelo

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.

The effects of CO2 on respiratory mechanics in anesthetized paralyzed humans.

BackgroundThere is little information concerning the carbon dioxide–related effects on respiratory mechanics in anesthetized, paralyzed subjects; however, hypocapnia or hypercapnia is often permitted in patients with severe brain injury or acute respiratory distress syndrome. Therefore, the carbon dioxide dependence of respiratory mechanics in healthy anesthetized, paralyzed subjects was investigated. MethodsInterrupter resistance (Rint), additional tissue viscoelastic resistance (&Dgr;R), and quasi-static elastance (Est) of lung (L) and chest wall were assessed by means of the rapid end-inspiratory occlusion method in two groups of seven healthy paralyzed subjects anesthetized with diazepam or isoflurane. They underwent ventilation with a fixed pattern and hyperoxic gas mixtures with different fractions of inspired carbon dioxide (Fico2) to produce a partial pressures of arterial carbon dioxide (Paco2) of 24.4 ± 3.4, 39.6 ± 3.2, and 62 ± 4.1 (SD) mmHg. ResultsChest wall mechanics and Est,L were unaffected by Paco2 changes. With diazepam anesthesia, Rint,L decreased linearly, with increasing Paco2, from 2.3 to 1.4 cm H2O · s · l−1, whereas &Dgr;R,L decreased from 2 to 1.7 cm H2O · s · l−1, though not significantly. With isoflurane anesthesia, the decrease of Rint,L (0.2 ± 0.5 cm H2O · s · l−1) was not significant, and &Dgr;RL remained unchanged. With diazepam, Rint,L was 45 (hypercapnia) to 110% (hypocapnia) greater than with isoflurane. ConclusionsChanges of Paco2 from 20–65 mmHg cause increasing bronchodilation in anesthetized, paralyzed subjects, this effect being attenuated or abolished by drugs (e.g., halogenated anesthetics) that depress smooth muscle tone substantially. The carbon dioxide bronchodilating effects are probably direct for peripheral structures and are paralleled by a tendency of lung tissue resistance to decrease. Because local Paco2-related changes in bronchomotor tone promote &OV0312;a/˙Q matching, this mechanism should be impaired by anesthetics that cause bronchodilation.

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.

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.

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.

Effects of Various Modes of Mechanical Ventilation in Normal Rats

Background:Recent studies in healthy mice and rats have reported that positive pressure ventilation delivered with physiological tidal volumes at normal end-expiratory volume worsens lung mechanics and induces cytokine release, thus suggesting that detrimental effects are due to positive pressure ventilation per se. The aim of this study in healthy animals is to assess whether these adverse outcomes depend on the mode of mechanical ventilation. Methods:Rats were subjected to 4 h of spontaneous, positive pressure, and whole-body or thorax-only negative pressure ventilation (N = 8 per group). In all instances the ventilatory pattern was that of spontaneous breathing. Lung mechanics, cytokines concentration in serum and broncho–alveolar lavage fluid, lung wet-to-dry ratio, and histology were assessed. Values from eight animals euthanized shortly after anesthesia served as control. Results:No evidence of mechanical ventilation–dependent lung injury was found in terms of lung mechanics, histology, or wet-to-dry ratio. Relative to control, cytokine levels and recruitment of polymorphonuclear leucocytes increased slightly, and to the same extent with spontaneous, positive pressure, and whole-body negative pressure ventilation. Thorax-only negative pressure ventilation caused marked chest and lung distortion, reversible increase of lung elastance, and higher polymorphonuclear leucocyte count and cytokine levels. Conclusion:Both positive and negative pressure ventilation performed with tidal volumes and timing of spontaneous, quiet breathing neither elicit an inflammatory response nor cause morpho-functional alterations in normal animals, thus supporting the notion of the presence of a critical volume threshold above which acute lung injury ensues. Distortion of lung parenchyma can induce an inflammatory response, even in the absence of volotrauma.

Influence of abdomen on respiratory mechanics in supine rabbits

Previous studies showed that abdominal evisceration has no effect on respiratory system compliance. We hypothesized that this could be related to lung distortion in eviscerated animals. Methods were developed for continuous recording of pleural pressure (Ppl) at various sites over the costal (co) and diaphragmatic lung surface (di) in acutely and chronically instrumented rabbits. We compared deltaPpl,co and deltaPpl,di recorded at mid-lung height during inflations in anesthetized, paralyzed supine rabbits before and after evisceration. Cranial and caudal deltaPpl.co were the same under all conditions. In intact animals, deltaPpl.co and deltaPpl,di were equal at all inflation volumes, whilst in eviscerated animals, deltaPpl,di were smaller than deltaPpl,co, the difference increasing with lung inflation. At any given volume, rib cage circumference (Crc) was smaller after evisceration, but the Crc deltaPpl,co relationship remained unchanged. These results are indicative of non-uniform lung expansion after evisceration and are consistent with model predictions based on cylindrical deformation and lung stress-strain relationship. This deformation should mimic the effect of a reduced lung compliance, keeping respiratory system compliance of eviscerated animals nearly normal. Similar deformation should have occurred also in intact rabbits during strong inspiratory efforts and in the erect posture, because lower Ppl,di than Ppl,co values were observed at the same lung height under these conditions.

Airway occlusion assessed by single breath N2 test and lung P-V curve in healthy subjects and COPD patients.

PURPOSE To determine whether the analysis of the slow expiratory transpulmonary pressure-volume (PL-V) curve provides an alternative to the single-breath nitrogen test (SBN) for the assessment of the closing volume (CV). METHODS SBN test and slow deflation PL-V curve were simultaneously recorded in 40 healthy subjects and 43 COPD patients. Onset of phase IV identified CV in SBN test (CVSBN), whereas in the PL-V curve CV was identified by: a) deviation from the exponential fit (CVexp), and b) inflection point of the interpolating sigmoid function (CVsig). RESULTS In the absence of phase IV, COPD patients exhibited a clearly discernible inflection in the PL-V curve. In the presence of phase IV, CVSBN and CVexp coincided (CVSBN/CVexp=1.04±0.04 SD), whereas CVsig was systematically larger (CVsig/CVexp=2.1±0.86). CONCLUSION The coincidence between CVSBN and CVexp, and the presence of the inflection in the absence of phase IV indicate that the deviation of the PL-V curve from the exponential fit reliably assesses CV.

150 years of blowing: Since John Hutchinson

Three recent advances in assessment of routine lung function are reviewed. In both normal subjects and patients with obstructive lung disease, the flows during the forced vital capacity (FVC) manoeuvre depend significantly on the pattern of the preceding inspiratory manoeuvre. Accordingly, the latter should be standardized in clinical and epidemiological studies. Although the nature of this phenomenon is not fully understood, stress relaxation of lung tissues probably plays the primary role. The negative expiratory pressure technique provides a simple and reliable tool for detecting expiratory flow limitation both at rest and during exercise. The method does not require body plethysmography or the patient’s cooperation and coordination, and can be applied in any desired body posture. A simple method for monitoring FVC performance has been developed. It allows detection of flow limitation during the FVC manoeuvre.