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Reduced expression of BMP-3 due to mechanical loading: a link between mechanical stimuli and tissue differentiation.

Mechanical signaling and BMP expression appear to be involved in controlling the differentiation of cartilage in fracture repair, but the connection between mechanics and BMP signaling is not known. In this study of rats, we used a bone chamber to see how BMP gene expression was changed by a mechanical loading regime that induces cartilage formation in this model. We compared the still undifferentiated tissue in loaded and unloaded chambers in the same rat regarding the expression of TGFbeta-1, BMP-2, 3, 4, 5, 6, 7, CDMP-1, 2 and ALK-2 and 3 by using RT-PCR normalized against GAPDH. We found expression of TGFbeta-1, BMP-2 and 4 in all specimens, and BMP 5-7 and CDMPs in none. 1 week after loading started, BMP-3 was strongly expressed in the unloaded control specimens in 7 of 8 animals, but detectable in only I of the contralateral loaded ones. After 2 weeks of loading, the BMP-3 expression pattern was less clear, but with both time groups taken together, there was still less BMP-3 expression on the loaded side in 9 rats, more in 1 and no difference in 5 (p = 0.01). ALK-2 at 1 week was expressed in all specimens expressing BMP-3 and in none of the others. At 2 weeks, ALK-2 was expressed in all specimens. Thus, a loading regime, known to induce cartilage in this model, caused down-regulation of BMP-3 and ALK-2. The results are consistent with the view that BMP-3 inhibits differentiation, as recently described. This role appears to be linked to the ALK-2 receptor. Most importantly, the results indicate a link between mechanical signaling and BMP expression such that mechanically-induced down-regulation of the inhibiting BMP-3 enabled the induction of cartilage.

Activin Receptors, Type I↗

Mechanical signaling through connective tissue: a mechanism for the therapeutic effect of acupuncture.

The mechanism of action of acupuncture remains largely unknown. The reaction to acupuncture needling known as 'de qi', widely viewed as essential to the therapeutic effect of acupuncture, may be a key to understanding its mechanism of action. De qi includes a characteristic needling sensation, perceived by the patient, and 'needle grasp' perceived by the acupuncturist. During needle grasp, the acupuncturist feels pulling and increased resistance to further movement of the inserted needle. We hypothesize that 1) needle grasp is due to mechanical coupling between the needle and connective tissue with winding of tissue around the needle during needle rotation and 2) needle manipulation transmits a mechanical signal to connective tissue cells via mechanotransduction. Such a mechanism may explain local and remote, as well as long-term effects of acupuncture.

Acupuncture Therapy↗

Effects of mechanical ventilation at low lung volume on respiratory mechanics and nitric oxide exhalation in normal rabbits.

Lung mechanics, exhaled NO (NOe), and TNF-alpha in serum and bronchoalveolar lavage fluid were assessed in eight closed and eight open chest, normal anesthetized rabbits undergoing prolonged (3-4 h) mechanical ventilation (MV) at low volume with physiological tidal volumes (10 ml/kg). Relative to initial MV on positive end-expiratory pressure (PEEP), MV at low volume increased lung quasi-static elastance (+267 and +281%), airway (+471 and +382%) and viscolelastic resistance (+480 and +294%), and decreased NOe (-42 and -25%) in closed and open chest rabbits, respectively. After restoration of PEEP, viscoelastic resistance returned to control, whereas airway resistance remained elevated (+120 and +31%) and NOe low (-25 and -20%) in both groups of rabbits. Elastance remained elevated (+23%) only in closed-chest animals, being associated with interstitial pulmonary edema, as reflected by increased lung wet-to-dry weight ratio with normal albumin concentration in bronchoalveolar lavage fluid. In contrast, in 16 additional closed- and open-chest rabbits, there were no changes of lung mechanics or NOe after prolonged MV on PEEP only. At the end of prolonged MV, TNF-alpha was practically undetectable in serum, whereas its concentration in bronchoalveolar lavage fluid was low and similar in animals subjected or not subjected to ventilation at low volume (62 vs. 43 pg/ml). These results indicate that mechanical injury of peripheral airways due to their cyclic opening and closing during ventilation at low volume results in changes in lung mechanics and reduction in NOe and that these alterations are not mediated by a proinflammatory process, since this is expressed by TNF-alpha levels.

Animals↗

Should mechanical ventilation be optimized to blood gases, lung mechanics, or thoracic CT scan?

This study was aimed at providing data for optimization of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). The effects of ventilation with positive end-expiratory pressure (PEEP) titrated to blood gases were studied by thoracic computed tomographic (CT) scans and lung mechanics measurements in eight patients. CT density histograms at end-expiration were used to investigate the effects of PEEP on three differently aerated zones. Static pressure-volume (P-V) curves were used to determine the deflection point above which baro-volotrauma (a combination of barotrauma and volotrauma) may occur. Peak pressures, plateau pressures, and lung volumes measured by Respitrace were compared with the deflection point. CT scan showed that PEEP increased "normally aerated" areas, decreased "nonaerated" areas, and did not change "poorly aerated" zones. No correlations were found between CT scan and either PaO2 or mechanical data. Pressure at the deflection point was lower than the usually recommended 35 to 40 cm H2O for peak pressure in four patients (range, 28 to 32 cm H2O). With regard to plateau pressures, only one patient was ventilated above the deflection point. However, monitoring of volumes showed that these four patients had an end-inspiratory volume above this point. We conclude that mechanical ventilation may be initially adjusted on the basis of blood gas values and then optimized on the basis of lung mechanics to limit the risk of baro-volotrauma.

Adolescent↗

Development of a novel compression tester and rheo-mechanical properties of wet-mass powder. I--Effect of kneading time on the rheo-mechanical properties.

In our previous paper [Watano S., et al., Chem. Phram. Bull., 49(1), 64-68, (2001)], a compaction tester was developed to quantitatively evaluate the water dispersion condition of wet kneaded masses prepared by a paddle type kneader. It was also demonstrated that the physical properties of pellets prepared by extrusion granulation after the kneading could be well predicted by the vertical pressure transmission obtained through the compaction tester. However, in this compression tester, the vertical pressure transmission was just obtained and rheological and mechanical properties (so called rheo-mechanical properties) of wet mass-powder that should be the most important to determine the deformation process were not well studied. In this study, a novel compression tester, which can measure both vertical and radial pressure transmissions, has been developed. Based on the compression test, mechanical property (Young's modulus) and rheological property (effective internal friction) of wet mass powder prepared by different kneading times were quantitatively investigated. Granules (pellets) were then obtained through the extrusion granulation and fluidized bed drying, and the physical properties (strength and disintegration time) of the obtained pellet were evaluated. The relationship between the granule (pellet) physical properties and the mechanical and rheological (rheo-mechanical) properties was analyzed.

Compressive Strength↗

Effect of thoracentesis on respiratory mechanics and gas exchange in the patient receiving mechanical ventilation.

BACKGROUND: This study reports the effect of thoracentesis on respiratory mechanics and gas exchange in patients receiving mechanical ventilation. STUDY DESIGN: Prospective. SETTING: University hospital. PATIENTS: Eight patient receiving mechanical ventilation with unilateral (n = 7) or bilateral (n = 1) large pleural effusions. INTERVENTION: Therapeutic thoracentesis (n = 9). MEASUREMENTS: Resistances of the respiratory system measured with the constant inspiratory flow interrupter method measuring peak pressure and plateau pressure, effective static compliance of the respiratory system (Cst,rs), work performed by the ventilator (Wv), arterial blood gases, mixed exhaled Pco2, and pleural liquid pressure (Pliq). RESULTS: Thoracentesis resulted in a significant decrease in Wv and Pliq. Thoracentesis had no significant effect on dynamic compliance of the respiratory system; Cst,rs; effective interrupter resistance of the respiratory system, or its subcomponents, ohmic resistance of the respiratory system and additional (non-ohmic) resistance of the respiratory system; or intrinsic positive end-expiratory pressure (PEEPi). Indices of gas exchange were not significantly changed by thoracentesis. CONCLUSIONS: Thoracentesis in patients receiving mechanical ventilatory support results in significant reductions of Pliq and Wv. These changes were not accompanied by significant changes of resistance or compliance or by significant changes in gas exchange immediately after thoracentesis. The reduction of Wv after thoracentesis in patients receiving mechanical ventilation is not accompanied by predictable changes in inspiratory resistance and static compliance measured with routine clinical methods. The benefit of thoracentesis may be most pronounced in patients with high levels of PEEPi.

Adult↗

Doxofylline and respiratory mechanics. Short-term effects in mechanically ventilated patients with airflow obstruction and respiratory failure.

To assess the short-term effects of a methylxanthine (doxofylline) on respiratory mechanics in mechanically ventilated patients with airway obstruction and respiratory failure, nine consecutive patients were examined within three days from the onset of mechanical ventilation. Flow, changes in pulmonary volume, and Paw were measured using a ventilator (Servo 900C). End-expiratory and end-inspiratory airway occlusion was performed to measure PEEPi, Cstrs, Rrsmax, and Rrsmin. Measurements were performed before and at 5, 15, and 30 minutes after an intravenous loading dose of doxofylline (5 to 6 mg/kg). We found that doxofylline determined, on the average, a marked decrease in respiratory resistance (Rrsmax and Rrsmin, -27.2 percent and -36.5 percent, respectively) without significant changes in Cstrs and Pmax. The PEEPi, reflecting pulmonary dynamic hyperinflation, was also significantly decreased by doxofylline (-41 percent, on the average). The Pmax was not reliable for evaluation of a single patient, since changes in the elastic pressure can offset changes in the resistive one. No patient experienced significant side effects due to doxofylline. We conclude that (1) the effects of therapy can be assessed noninvasively at bedside in critically ill patients; (2) doxofylline is a rapid and efficient bronchodilator in mechanically ventilated patients with ARF and airflow obstruction; and (3) the decrease in the respiratory resistance and PEEPi, associated with an improved mechanical efficiency of the respiratory muscles at a lower pulmonary volume, can provide better conditions for the patient-ventilator interaction and for weaning.

Bronchodilator Agents↗

Molecular and cellular mechanisms of mechanical stress-induced cardiac hypertrophy.

Congestive heart failure is one of the major issues for cardiologists. Since cardiac hypertrophy deteriorates into heart failure, it is important to elucidate the mechanisms of cardiac hypertrophy. Hemodynamic overload, namely mechanical stress, is a major cause for cardiac hypertrophy. Mechanical stress induces various hypertrophic responses such as activation of phosphorylation cascades of many protein kinases, expression of specific genes and an increase in protein synthesis. During this process, secretion and production of vasoactive peptides such as angiotensin II and endothelin-1, are increased and play critical roles in the induction of these hypertrophic responses. Recently, a Ca2+ dependent protein kinase, CaMK, and a Ca2+ dependent protein phosphatase, calcineurin, have attracted great attention as critical molecules that induce cardiac hypertrophy. In this review, we described the mechanisms by which mechanical stress induces cardiac hypertrophy, especially focusing on the role of calcineurin in the development of cardiac hypertrophy.

Angiotensin II↗

In vitro response of chondrocytes to mechanical loading. The effect of short term mechanical tension.

Chick epiphyseal chondrocytes were grown in high density cultures for 14 days, after which the cell layers were placed in a cyclical stretching apparatus and subjected to a strain of 5.5% at a frequency of 0.2 Hz. There was a 1.4- and 1.7-fold increase in the incorporation of 35SO4 and 14C-glucosamine, respectively, into glycosaminoglycans in cultures subjected to mechanical loading for 24 h. No significant change was observed in the hydrodynamic size of the proteoglycans synthesized by chondrocytes subjected to mechanical loading. In this time period there was no increase in 3H-glycine incorporation into acid-insoluble protein, but there was a 2.4-fold increase of 3H-thymidine into DNA in cultures subjected to tensional strain. Concomitant with these changes, the cellular levels of cyclic AMP increased 2.2 times in the mechanically loaded cultures. This is discussed as a possible mechanism whereby chondrocytes respond to mechanical stimuli.

Animals↗

Pulmonary mechanics in preterm neonates with respiratory failure treated with high-frequency oscillatory ventilation compared with conventional mechanical ventilation.

Pulmonary mechanics were measured in 43 preterm neonates (mean +/- SD values of birth weight 1.2 +/- 0.3 kg, gestational age 30 +/- 2 weeks) with respiratory failure who were concurrently randomly assigned to receive conventional mechanical ventilation (n = 22) or high-frequency ventilation (n = 21). The incidence of bronchopulmonary dysplasia was comparable in the two groups (high-frequency ventilation 57%, conventional ventilation 50%). Pulmonary functions were determined at 0.5, 1.0, 2.0, and 4.0 weeks postnatal ages. Data were collected while subjects were in a nonsedated state during spontaneous breathing. These sequential data show similar patterns of change in pulmonary mechanics during high-frequency ventilation and conventional mechanical ventilation irrespective of gestational age, birth weight stratification, or bronchopulmonary dysplasia. There was no significant difference in the pulmonary functions with either mode of ventilation during the acute phase (less than or equal to 4 weeks) of respiratory disease. When evaluated by the clinical diagnosis of bronchopulmonary dysplasia, the pulmonary data suggested a less severe dysfunction in the high-frequency oscillatory ventilation-treated bronchopulmonary dysplasia group compared with the conventional mechanical ventilation-treated group. These results indicate that high-frequency oscillatory ventilation in preterm neonates does not reduce the risk of acute lung injury; however, the magnitude of the pulmonary dysfunction in the first 2 weeks of life merits a reevaluation.

Bronchopulmonary Dysplasia↗

The effects of bedside pulmonary mechanics testing during infant mechanical ventilation: a retrospective analysis.

We examined the effects of regular bedside testing of pulmonary mechanics (PM) on the outcome of 468 acutely ill, mechanically ventilated neonates. During the first of two 18-month study periods, 217 infants were mechanically ventilated without the assistance of PM measurements. During the second 18-month period, 251 infants were ventilated with the assistance of at least daily PM measurements. Using data obtained from the PM tests, we adjusted the infants' ventilators to maintain tidal volume, inspiratory time, and pressure-volume loops within predetermined limits. With the exception of the PM measurements, given the limitations of retrospective analyses, both groups of infants received identical medical and nursing care. The infants ventilated with the assistance of PM testing developed fewer pneumothoraces (4.0%; 10/251) vs. no PM testing, 10.1% (22/217); P < 0.05 by Chi-square analysis]. Infants weighing less than 1,500 g ventilated with the assistance of PM measurements had less intraventricular hemorrhage (IVH) overall, most notably, less grades I and II IVH (total IVH-PM testing, 39.1% vs. no PM testing, 65.7%; P < 0.01; Grades I-II IVH-PM testing, 30.4% vs. no PM testing, 54.9%; P < 0.01). IVH incidence was decreased independent of pneumothorax occurrence. Survival rates, incidences of bronchopulmonary dysplasia, and durations of mechanical ventilation and hospitalization were similar. This retrospective analysis suggests that PM testing during infant mechanical ventilation reduces common acute ventilator-associated complications.

Bronchopulmonary Dysplasia↗

Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury.

Fasted Wistar rats were subjected to either a mild mechanical injury, 6 min of transient forebrain ischemia, or a mild mechanical injury followed 1 h later by 6 min of forebrain ischemia. EEG and evoked potentials were assessed intermittently and morphological analyses were performed after 7 days postinjury survival. In all groups complete qualitative recovery of electrical activity and general behavior was observed with 7-day survival. However, rats subjected to combined concussion and ischemia displayed EEG spike activity and a delayed return of EEG and evoked potentials during acute recovery not evident in other groups. No overt neuronal cell loss was seen in trauma alone and was minimal or absent in ischemia alone. However, extensive bilateral CA1 and subicular pyramidal cell loss was found in the septal and mid-dorsal hippocampi in the combined trauma and ischemia group. In contrast, no overt axonal injury was found in any group. We conclude that even mild mechanical injury can potentiate selective ischemic hippocampal neuronal necrosis in the absence of overt axonal injury. This potentiation also occurs in conjunction with more generalized electrophysiological disturbances such as EEG evidence of postischemic neuronal hyperactivity suggesting that mild concussion may also decrease the threshold for post-ischemic neuronal excitation. These results suggest the potential of this model for examining common or different injury mechanisms in mechanical and ischemic brain injury.

Animals↗

An energy 'sources' and 'fractions' approach to the mechanical energy expenditure problem--III. Mechanical energy expenditure reduction during one link motion.

Mechanical energy economy and transformation during one link motion are analyzed on the basis of the theory developed in the previous publications (parts I and II of this series, J. Biomechanics 19, 287-300). The 'compensation coefficient' characterizing mechanical energy economy is introduced. The attempts to estimate MEE using only energy curves and neglecting the powers of real sources of energy implicitly lead to replacement of real force and moment systems by the systems reduced to the centers of mass. But such an unintentional substitution of imaginary sources for real ones, specifically, the reduction of forces acting on the link to the equivalent system, changes estimates of mechanical energy expenditure (MEE). That is why the methods of calculating MEE economy based on the determination of so-called 'quasi-mechanical' work (the sum of the kinetic and potential energy increases per one cycle of motion) are not correct. There are two mechanisms to reduce the MEE using the antiphase fluctuations (corresponding to energy transformations) of the (a) rotational and translational fractions of the total energy (at the expense of the F-sources); (b) potential and kinetic energies (at the expense of the mg-source).

Biomechanical Phenomena↗

Mechanical restitution in isolated mammalian myocardium: species differences and underlying mechanisms.

Ventricular myocardium was obtained from guinea-pig, ferret and human hearts. In each case small strips were mounted isometrically in a tissue bath and superfused with a physiological saline at 37 degrees C. The preparations were stimulated at 1 Hz and ectopic stimuli of different preceding intervals were given. The relationship between the force produced by the ectopic contraction and the duration of the preceding interval was plotted to form mechanical restitution curves (MRC). In the guinea-pig the MRC is described by a rapid recovery phase with an exponential time constant of 220 +/- 22.7 ms (mean +/- S.E.M.) followed by a decay (28.5 +/- 8.4 s). In ferret and man the rising phase is described by two exponentials (192.5 +/- 43.2 ms and 4.4 +/- 1.5 s in the ferret; 259.7 +/- 45.2 ms and 3.0 +/- 1.0 s in man). The decay phase is slower in ferret (22 +/- 156 s, P less than 0.02) and man (177 +/- 70 s, P less than 0.002) than in guinea-pig. There was no significant difference between the time constants of the rapid recovery phase of mechanical restitution in each species. The time constant of the rapid recovery phase (tau 1) was abbreviated by ryanodine, ouabain and adrenaline in human myocardium and by ryanodine alone in guinea-pig. Verapamil increased tau 1 in both species. The decay time constant (tau 3) was prolonged by ouabain, verapamil and by increasing extracellular [Ca2+] in human myocardium and by ouabain and verapamil in guinea-pig. The recovery of the second inward current in human myocardium was not correlated to the recovery of mechanical function. It is suggested that tau 1 is dependent on the recycling of Ca2+ within the cell as well as the reactivation of the second inward current. The decay phase, tau 3, is dependent on the rate of Ca2+ efflux from the cell, possibly via a Na+/Ca2+ exchange mechanism. The mechanisms underlying the slow recovery time constant, tau 2, are unclear but it is important to calculate tau 2 for the proper evaluation of tau 1.

Animals↗

Mechanisms of mechanical stress-induced Ca(2+)-mobilization sensitized by lysophosphatidic acid in cultured smooth muscle cells.

We have previously reported that lysophosphatidic acid (LPA) sensitizes mechanical stress-induced cytosolic free Ca2+ concentration ([Ca2+]i) response related to Ca2+ entry through Gd(3+)-sensitive ion channels (Biochem. Biophys. Res. Commun. 208 19-25 1995). Here we examined the contribution of Ca2 release from intracellular stores to the mechanical stress-induced [Ca2+]i response sensitized by LPA in cultured longitudinal muscle cells from guinea pig ileum. Although the percentage of responsive cells to the mechanical stress in the presence of 30 nM LPA declined by decreasing extracellular Ca2+ concentration to less than 20 microM, the amplitude of the mechanical stress-induced [Ca2+]i transient did not depend on extracellular Ca2+ concentrations (10 microM-1.8 mM). The [Ca2+]i transient was completely abolished by treatment with thapsigargin. In addition, the amplitude of the [Ca2+]i transient gradually decreased after ryanodine and caffeine treatment. These results indicate that the mechanical stress-induced [Ca2+]i transient in the presence of LPA is mainly due to Ca2+ release from ryanodine-sensitive intracellular stores and may be triggered by Ca2+ influx through Gd(3+)-sensitive ion channels.

Animals↗

Mechanism of dioxygen formation catalyzed by vanadium bromoperoxidase from Macrocystis pyrifera and Fucus distichus: steady state kinetic analysis and comparison to the mechanism of V-BrPO from Ascophyllum nodosum.

Vanadium bromoperoxidase (V-BrPO) catalyzes the oxidation of bromide by hydrogen peroxide, which results in the bromation of appropriate organic substrates or the formation of dioxygen, in the absence of an organic substrate and under certain other conditions. The mechanism of the bromide-assisted disproportionation of hydrogen peroxide catalyzed by V-BrPO, which is the reaction that forms dioxygen, has been investigated for V-BrPO isolated from two new marine algal sources, Macrocystis pyrifera and Fucus distichus. The steady state kinetic studies have been performed under conditions of 0.02-40 mM H2O2, 1-500 mM Br- and pH 4.0-8.0. The rate data is consistent with a substrate-inhibited bi bi ping pong mechanism, in which the substrate bromide, is also an inhibitor by a noncompetitive-type mechanism. Bromide inhibits V-BrPO from M. pyrifera most strongly at pH 5.0-5.5 and V-BrPO from F. distichus most strongly at pH 5.5-6.0. The steady state mechanism of the Macrocystis and the Fucus enzymes are compared to the mechanism of the bromide-assisted disproportionation of hydrogen peroxide catalyzed by V-BrPO from Ascophyllum nodosum. In addition, the substrate hydrogen peroxide can also inhibit V-BrPO.

Catalysis↗

The mechanism of lamellar-to-inverted hexagonal phase transitions in phosphatidylethanolamine: implications for membrane fusion mechanisms.

We studied the mechanism of the lamellar-to-inverted hexagonal (L alpha/H[II]) phase transition, using time-resolved cryotransmission electron microscopy (TRC-TEM), 31P-NMR, and differential scanning calorimetry. The transition was initiated in dispersions of large unilamellar vesicles of dipalmitoleoyl phosphatidylethanolamine (DiPoPE). We present evidence that the transition proceeds in three steps. First, many small connections form between apposed membranes. Second, the connections aggregate within the planes of the bilayers, forming arrays with hexagonal order in some projections. Third, these quasihexagonal structures elongate into small domains of H(II) phase, acquiring lipid molecules by diffusion from contiguous bilayers. A previously proposed membrane fusion mechanism rationalizes these results. The modified stalk theory predicts that the L alpha/H(II) phase transition involves some of the same intermediate structures as membrane fusion. The small interbilayer connections observed via TRC-TEM are compatible with the structure of a critical intermediate in the modified stalk mechanism: the trans monolayer contact (TMC). The theory predicts that 1) TMCs should form starting at tens of degrees below TH; 2) when TMCs become sufficiently numerous, they should aggregate into transient arrays like the quasihexagonal arrays observed here by TRC-TEM; and 3) these quasihexagonal arrays can then elongate directly into H(II) phase domains. These predictions rationalize the principal features of our data, which are incompatible with the other transition mechanisms proposed to date. Thus these results support the modified stalk mechanism for both membrane fusion and the L alpha/H(II) phase transition. We also discuss some implications of the modified stalk theory for fusion in protein-containing systems. Specifically, we point out that recent data on the effects of hydrophobic peptides and viral fusion peptides on lipid phase behavior are consistent with an effect of the peptides on TMC stability.

Biophysical Phenomena↗

Volume and flow dependence of respiratory mechanics in mechanically ventilated COPD patients.

Volume and flow dependencies of respiratory mechanics are examined in 10 COPD patients under mechanical ventilation (MV) at 3 levels of externally applied PEEP (PEEPe). Airways pressure (Paw), flow (V') and volume (V) data are analyzed according to (1) the linear and (2) a non-linear model, accounting for volume dependence of elastance and for flow and volume dependence of resistance. The models' fitness to data is assessed by the regression errors. Non-linear modelling fits significantly better to data, while the difference of fitness decreases with PEEPe. Linear mechanics are not significantly different between the 3 levels of PEEPe. A positive volume dependence of elastance observed at 0, decreases at 5 and increases again at 10 hPa of PEEPe. A seriously negative volume dependence of resistance at 0 turned to positive with PEEPe. These dependencies of respiratory mechanics during COPD under MV, show that the present non-linear respiratory mechanical monitoring may help for better and less risky adjustment of PEEPe.

Female↗