Increase In Dynamic Compliance Research Articles

Effect of cross-linking and hydration on microscale flat punch indentation contact to collagen-hyaluronic acid films in the viscoelastic limit

The properties of the extracellular matrix (ECM) have profound impact upon cell behaviour. As an abundant protein in mammals, collagen is a desirable base material to engineer an ECM tissue scaffold, but its structural weakness generally requires molecular crosslinking or incorporation of additional ECM-based macromolecules such as glycosaminoglycans. We have performed microscopic indentation to test collagen films under dry and aqueous conditions prepared with different levels of physical and chemical crosslinking. Our technique isolates intrinsic properties of the poro-viscoelastic matrix in a regime minimizing the influence of drainage hydrodynamics and allows direct measurement of the effect of hydrating a specific sample. A doubling of the effective stress-strain stiffness under crosslinking could be directly correlated to structural changes in X-ray diffraction spectra, while electron microscopy revealed possible fibril bridging mechanisms explaining observed toughness. Overall, an intrinsic viscoelastic stress-strain response of collagen under various conditions of cross-linking was observed for both dry and wet conditions, with the latter most affected by indentation rate. Under creep testing, a three order of magnitude increase in dynamic compliance and factor three reduction in relaxation time was found going from the dry to hydrated state. When fitted to a simple viscoelastic model, crosslinking showed a tendency to decrease relaxation time in both states, but reduced dynamic compliance only in the hydrated case. This suggests a reduced role of virtual crosslinks under hydration. This is the first study reporting consistent mechanical testing of dry and hydrated ECM-derived biomaterials, accessing the intrinsic material mechanics under in vivo-like conditions. Statement of SignificanceThis manuscript presents new insights into the effect of crosslinking on mechanical properties of dry and hydrated collagen intended for tissue scaffolding applications. A novel microscopic indentation technique allowed testing of the poro-viscoelastic matrix isolated in a regime minimizing the influence of drainage hydrodynamics, so direct comparison of the effect of hydration on the intrinsic material behaviour to could be made. A variety of experimental techniques including X-ray diffraction, infrared spectroscopy, and scanning electron and atomic force microscopy were used to augment the mechanical testing. The results of creep testing were numerically analysed using a four-component viscoelastic model. This is the first mechanical testing of dry and hydrated ECM-derived biomaterials, accessing the intrinsic material mechanics under in vivo-like conditions.

The Effects of Alveolar Recruitment Maneuver Versus Low Tidal Volume Ventilation on Oxygenation and Lung Mechanics in Patients Undergoing Laparoscopic Surgeries: A Prospective Randomized Controlled Study.

Different ventilatory strategies have been studied to improve gas exchange and compliance of the lungs in patients undergoing laparoscopic surgeries. This study aimed to test the impact of alveolar recruitment maneuver versus low tidal volume ventilation combine with PEEP on arterial oxygenation and lung mechanics in patients undergoing laparoscopic surgeries. Sixty patients were randomly allocated into three equal groups according to the type of ventilation strategy used during surgery. In the control group, patients received conventional volume-controlled ventilation with 10ml/Kg VT and zero PEEP (ZEEP). In group II ( LTV ), patients received low tidal volume ventilation in the form of 6-8 ml/Kg VT and PEEP 5cmH2O. In group III (REC), patients received 6-8 ml/Kg and recruitment maneuvers were done every 10 minutes after intubation till extubation by manual inflation to 40cmH2O peak inspiratory pressure for 15 seconds then the patient was placed back to the same ventilation settings with PEEP of 5cmH2O. The primary outcome is the dynamic compliance. The secondary outcome measures include PaO2, PH, PCO2, SPO2, HR and MAP. Demographic characteristics and duration of surgery were comparable among groups. PaO2 was highly significantly increased (p <0.001) in the recruitment group (Rec) compared to the conventional group (C) and low tidal volume ventilation group (LTV). There was significant increase in dynamic compliance in the recruitment group (REC) compared with the conventional (C) and low tidal volume (LTV) groups. SpO2, PaCO2 showed a highly statistical significance differences between the three ventilated groups. There were no statistically significant differences between the three ventilated groups in terms of PH. There were no statistically significant differences between the three ventilated groups in terms of Mean arterial blood pressure and HR. repeated recruitment maneuvers combined with 5 cm H2O of PEEP increased respiratory system compliance and PaO2 in patients undergoing laparoscopic surgeries without hemodynamics adverse effects.

Effect of Cross-Linking and Hydration on Microscale Flat Punch Indentation of Collagen-Hyaluronic Acid Films in the Viscoelastic Limit

The properties of the extracellular matrix (ECM) have profound impact upon cell behaviour. As an abundant protein in mammals, collagen is a desirable base material to engineer an ECM tissue scaffold, but its structural weakness generally requires molecular crosslinking or incorporation of additional ECM-based macromolecules such as glycosaminoglycans. We have performed microscopic indentation to test collagen films under dry and aqueous conditions prepared with different levels of physical and chemical crosslinking. Our technique isolates intrinsic properties of the poro-viscoelastic matrix in a regime minimizing the influence of drainage hydrodynamics and allows direct measurement of the effect of hydrating a specific sample. A doubling of the effective stress-strain stiffness under crosslinking could be directly correlated to structural changes in X-ray diffraction spectra, while electron microscopy revealed possible fibril bridging mechanisms explaining observed toughness. Overall, an intrinsic viscoelastic stress-strain response of collagen under various conditions of cross-linking was observed for both dry and wet conditions, with the latter most affected by indentation rate. Under creep testing, a three order of magnitude increase in dynamic compliance and factor three reduction in relaxation time was found going from the dry to hydrated state. When fitted to a viscoelastic model, crosslinking showed a tendency to decrease relaxation time but gave no recognizable trend to dynamic compliance. This is the first reported approach that allows for repeatable mechanical data on dry and hydrated ECM-derived biomaterials, accessing the intrinsic material mechanics under in vivo-like conditions.

In-situ observation of evolving microstructural damage and associated effective electro-mechanical properties of PZT during bipolar electrical fatigue

We investigate the fatigue behavior of bulk polycrystalline lead zirconate titanate (PZT) during bipolar electric field cycling. We characterize the frequency- and cycle-dependent degradation in both the effective electro-mechanical properties (specifically, the electrical hysteresis and the macroscopic viscoelastic stiffness and damping measured by Broadband Electromechanical Spectroscopy, BES) and the microstructural damage evolution (quantified via scanning electron microscopy). The BES setup enables the mechanical characterization while performing electrical cycling so as to measure the evolving viscoelasticity without remounting the sample; particularly measuring the viscoelastic damping allows us to gain insight into the ferroelectric domain wall activity across the full electric hysteresis and over the full range of cycles. A clear dependence on the electric cycling frequency is observed in the rates of degradation of all measured properties including an up to 10% increase in dynamic compliance and a 70% decrease in electric displacement magnitude. We quantify the evolving micro-crack density across wide ranges of numbers of cycles and compare with changes in the effective compliance. Interestingly, the observed strong degradation in the ferroelectric hysteresis is contrasted by relatively mild changes in the effective viscoelastic moduli, while samples clearly indicate increasing levels of micro-damage.

Effect of Ultrasound-Guided Thoracocentesis on Clinical and Physiological Outcomes in Mechanically Ventilated Patients

Background: Pleural effusions are common in critically ill patients, causes are multifactorial. Mechanical ventilation and critical illness lead to disturbance of the normal physiological processes which regulate pleural fluid homeostasis. Ultrasound can detect small volume of pleural effusion up to 20 mL. Aim of the work: We investigated the influence of large pleural effusion drainage on oxygenation, hemodynamics, and respiratory mechanics in mechanically ventilated patients. Methodology: We performed a prospective observational study on 65 mechanically ventilated patients examining the effects of large pleural fluid drainage on oxygenation; PaO2/FiO2 and Respiratory mechanics; peak inspiratory pressures, plateau pressures, dynamic compliance and total PEEP. Hemodynamics and complications also recorded at baseline, 6 h and 24 h after drainage. Results: Among 65 patients, the mean volume of effusion drained was (1868 ± 640) ml at 24 h. Uncomplicated pneumothorax occurred in two patients. When compared baseline; 6 h and 24 h after drainage,PaO2/FiO2 ratio significantly improved (196.69 ± 34.27, 227.02 ± 35.81, 269.78 ± 48.39; p<0.001), with a decrease in peak inspiratory pressure (38.23 ± 5.71, 34.14 ± 4.70, 29.89 ± 4.58 cm H2O, p<0.001) and plateau pressures (21.06 ± 3.47, 18.77 ± 3.17, 15.49 ± 2.91 cm H2O, p<0.001) and a large increase in dynamic compliance (17.48 ± 4.12, 21.79 ± 4.47, 26.77 ± 4.94 ml/cm H2O, p<0.001). Hemodynamics were not changed by drainage apart from respiratory rate which decreased significantly (19.4 ± 5.5, 17.4 ± 5, 16.5 ± 6.8 breaths/min, P=0.019). Conclusions: Ultrasound pleural effusion drainage in mechanically ventilated patients is safe. It appears to ameliorate oxygenation and respiratory mechanics and reducing the respiratory rate without affecting hemodynamics.

Aging-related changes in respiratory system mechanics and morphometry in mice.

Previous work investigating respiratory system mechanics in mice has reported an aging-related increase in compliance and mean linear intercept (Lm). However, these changes were assessed using only a young (2-mo-old) and old (20- and 26-mo-old) group yet were interpreted to reflect a linear evolution across the life span. Therefore, to investigate respiratory system mechanics and lung morphometry across a more complete spectrum of ages, we utilized 2 (100% survival, n = 6)-, 6 (100% survival, n = 12)-, 18 (90% survival, n = 12)-, 24 (75% survival, n = 12)-, and 30 (25% survival, n = 12)-mo-old C57BL/6 mice. We found a nonlinear aging-related decrease in respiratory system resistance and increase in dynamic compliance and hysteresis between 2- and 24-mo-old mice. However, in 30-mo-old mice, respiratory system resistance increased, and dynamic compliance and hysteresis decreased relative to 24-mo-old mice. Respiratory system impedance spectra were measured between 1-20.5 Hz at positive end-expiratory pressures (PEEP) of 1, 3, 5, and 7 cmH2O. Respiratory system resistance and reactance at each level of PEEP were increased and decreased, respectively, only in 2-mo-old animals. No differences in the respiratory system impedance spectra were observed in 6-, 18-, 24-, and 30-mo-old mice. Additionally, lungs were fixed following tracheal instillation of 4% paraformaldehyde at 25 cmH2O and processed for Lm and airway collagen deposition. There was an aging-related increase in Lm consistent with emphysematous-like changes and no evidence of increased airway collagen deposition. Accordingly, we demonstrate nonlinear aging-related changes in lung mechanics and morphometry in C57BL/6 mice.

Senescent Cells Contribute to the Physiological Remodeling of Aged Lungs.

Age-associated decline in organ function governs life span. We determined the effect of aging on lung function and cellular/molecular changes of 8- to 32-month old mice. Proteomic analysis of lung matrix indicated significant compositional changes with advanced age consistent with a profibrotic environment that leads to a significant increase in dynamic compliance and airway resistance. The excess of matrix proteins deposition was associated modestly with the activation of myofibroblasts and transforming growth factor-beta signaling pathway. More importantly, detection of senescent cells in the lungs increased with age and these cells contributed toward the excess extracellular matrix deposition observed in our aged mouse model and in elderly human samples. Mechanistic target of rapamycin (mTOR)/AKT activity was enhanced in aged mouse lungs compared with those from younger mice associated with the increased expression of the histone variant protein, MH2A, a marker for aging and potentially for senescence. Introduction in the mouse diet of rapamycin, significantly blocked the mTOR activity and limited the activation of myofibroblasts but did not result in a reduction in lung collagen deposition unless it was associated with prevention of cellular senescence. Together these data indicate that cellular senescence significantly contributes to the extracellular matrix changes associated with aging in a mTOR 1-dependent mechanism.

ABSTRACT 392

Background and aims: A lung recruitment maneuver (RM) is an applied transient increase in transpulmonary pressure intended to increase end-expiratory lung volume and re-expand collapsed lung units. Due to the potential detrimental effects on hemodynamics by the maneuvers, there is very limited data in its use in the pediatric cardiac patient population. Aims: To demonstrate safety of lung RM in post-operative pediatric cardiac patients and evaluate the ability of lung RM to improve pulmonary compliance. Methods: A retrospective chart review was performed on a convenience sample of 62 post-operative cardiac surgical patients. IRB approval was obtained. Study patients were selected from patients who met criteria between June 2011 to May 2012 during which time a RM protocol was implemented at a free standing children’s hospital. Due to RMs generating a temporary increase in intrathoracic pressure, physiologic variables were monitored before, during, and after the RM. Results: RMs were safe and well-tolerated hemodynamically, and there was no significant change in oxygen saturation, blood pressure or heart rate during the maneuvers. RMs resulted in a post-maneuver increase in dynamic pulmonary compliance from 0.48 to 0.63 mL / cmH2O / kg (P< .001; 95% CI). An increase in dynamic compliance following completion of the RM was seen in all 62 patients. Conclusions: In this retrospective study, RMs were well tolerated by post-operative cardiac surgical patients. RMs also increased pulmonary compliance, and had no noticeable detrimental hemodynamic effects. These findings suggest RM protocols in post-operative pediatric cardiac surgical patients could be investigated in a prospective study.

A physiologic and biochemical profile of clinically rejected lungs on a normothermic ex vivo lung perfusion platform

BackgroundAlthough ex vivo lung perfusion (EVLP) is increasingly being used to evaluate and manipulate potential donor lungs before lung transplantation (LTx), data on the biochemistry of lungs during EVLP are limited. In this study, we examined the physiology and biochemistry of human lungs on an EVLP circuit. MethodsWe recovered unallocated double lungs in standard fashion and split them into single lungs. All lungs received a nebulized arginase inhibitor, 2-S-amino-6-boronohexanoic acid (ABH), at either the onset (n = 6) or after 3 h (n = 8) of EVLP. Serial biochemical analysis included levels of arginase, endogenous nitric oxide synthase (eNOS), cyclic guanosine monophosphate, and reactive oxygen species. We considered lungs transplantable if they sustained a PaO2:FiO2 ≥ 350 in addition to stable pulmonary function during EVLP. ResultsWe recovered a total of 14 single lungs. We deemed three single lungs from different donors to be transplantable after EVLP. These lungs had superior oxygenation, lower carbon dioxide, and more stable pulmonary artery pressures. Transplantable lungs had higher baseline levels of eNOS and higher final levels of cyclic guanosine monophosphate than non-transplantable lungs. Early ABH administration was associated with a transient increase in dynamic compliance. ConclusionsIn this biochemical characterization of lungs deemed unsuitable for LTx, early levels of eNOS and late levels of cyclic guanosine monophosphate appear to be associated with improved allograft function during EVLP. In addition, nebulized ABH is associated with a significant increase in dynamic compliance. These data suggest that biochemical markers during EVLP may predict acceptable allograft function, and that this platform can be used to biochemically manipulate donor lungs before LTx.

506 Heliox in the Management of Neonates with Meconium Aspiration Syndrome (MAS)

The aim of the study was to asses the influence of short-term mechanical ventilation with heliumoxygen mixture (heliox) in newborns with MAS on basic vital signs, oxygenation, acid-base balance and respiratory mechanics.The study was carried out in newborns with respiratory failure requiring mechanical ventilation due to MAS. Patients were ventilated using PC-SIMV. Parameters of mechanical ventilation, respiratory mechanics, oxygenation, acid-base balance and vital signs were recorded during three periods of one hour before, during and after heliox ventilation.Nine newborns with MAS were enrolled in the study. Mechanical ventilation with heliox did not affect vital signs, and infants' general condition remained stable during and after ventilation with heliox. Mechanical ventilation with heliox was associated with a statistically significant increase in dynamic compliance(mean 0,4 vs 0,53ml/cmH2O). Heliox caused an increase in tidal volume(mean 5,57 vs 6,84ml/kg)and minute ventilation(mean 0,87 vs 0,95l)but this was not statistically significant. Mechanical ventilation with heliox allowed the use of significantly lower fractions of inspired oxygen(mean 0,62 vs 0,35), with a significant decrease in the oxygenation index(mean 8,09 vs 4,26)and alveolararterial oxygen tension difference(mean 320,04 vs 127,65mmHg).A significant increase in pH(mean 7,34 vs 7,38) was also observed with a concomitant decrease in PaCO2(mean 43,4 vs 39,9)which was not statistically significant. Beneficial effects of heliox reversed after ventilation with this gas mixture was stopped. Patients required higher FiO2(mean 0,35 vs 0,38), OI(mean 4,26 vs 5,27)and AaDO2(mean 127,65 vs 159,6)increased. There was also a significant decrease in oxygen saturation(mean 93,69 vs 91,63).Ventilation with heliox had a positive effect on the selected parameters of oxygenation, acid-base balance and respiratory mechanics in newborns with MAS.

Efficacy and safety of intrapulmonary percussive ventilation superimposed on conventional ventilation in obese patients with compression atelectasis

Purpose To investigate the efficacy and safety of intrapulmonary percussive ventilation (IPV) in obese patients, we assessed their respiratory and hemodynamic functions during IPV superimposed on conventional ventilation. Materials and Methods Ten obese patients with acute respiratory failure due to compression atelectasis who had not improved by conventional ventilation were treated with IPV. Hemodynamic parameters, ventilator settings, and intracranial pressure (n = 1) were recorded every hour. Arterial blood gas was analyzed every 3 hours. The efficacy and safety of IPV was assessed at the start of weaning. Results Before IPV, Pa o 2/F io 2 ratio remained low (189 ± 63 mm Hg), which significantly increased to 243 ± 67 mm Hg at 3 hours from the initiation of IPV ( P < .01). Furthermore, it continuously increased to 280 ± 50 mm Hg at 24 hours ( P < .01). Intrapulmonary percussive ventilation induced significant increase in dynamic compliance from control value of 30 ± 8 mL/cm H 2O at 0 hours to 35 ± 9 mL/cm H 2O at 12 hours ( P < .05) and to 38 ± 8 mL/cm H 2O at 24 hours ( P < .01). Heart rate and mean arterial pressure were not significantly changed during IPV. Improvement of compression atelectasis was confirmed by their chest computed tomographic scans. Adverse effects such as pneumothorax and intracranial hypertension were not seen. Conclusions These results demonstrated that IPV was effective and safe in improving compression atelectasis without adverse effects in obese patients.

Mechanics of Breathing after Surgical Ligation of Patent Ductus arteriosus in Newborns with Respiratory Distress Syndrome

The aim of the study was to detect changes in pulmonary function following ligation of a patent ductus arteriosus (PDA). Pulmonary function was recorded in 16 newborns (birth weight 1,081 ± 166 g, gestational age 27.6 ± 1.7 weeks) before and after ligation. No change in resistance of airways or mean airway pressure was observed. We found an increase in dynamic compliance (Cdyn) of 77% (p < 0.01), in tidal volume (TV) of 29% (p = 0.004), and in minute ventilation (MV) of 17% (p < 0.01) after the procedure. We demonstrated that pulmonary function improves after surgical ligation of the PDA. Because of considerable variation in intubated and spontaneously breathing premature newborns, we recommend the analysis of three main parameters: Cdyn, TV and MV for estimation of pulmonary mechanics in these infants.

Partial liquid ventilation and nitric oxide in congenital diaphragmatic hernia

Purpose: In congenital diaphragmatic hernia (CDH) there is immature lung development with a resulting clinical picture of pulmonary hypoplasia, surfactant deficiency, and pulmonary hypertension. Pulmonary hypoplasia and surfactant deficiency both have been successfully treated using partial liquid ventilation (PLV). Pulmonary hypertension associated with CDH has proven difficult to treat, but inhaled nitric oxide, which is a potent highly selective pulmonary vasodilator, may have potential. The aim of this study was to assess PLV in CDH and to document the effect of nitric oxide when administered through perfluorocarbon. Methods: This study using the lamb CDH model consisted of two groups; a conventional mechanically ventilated (CMV) group and a PLV group. At 1 and 3 hours, nitric oxide (80 ppm) was given for 15 minutes. Data collected included blood gases, pulmonary function tests, pulmonary and systemic blood pressure. Results: After 30 minutes of ventilation, blood gases in the PLV group were all significantly improved ( P < .001): pH, CMV 6.92 ± 0.15 versus PLV 7.24 ± 0.11; P CO 2 , CMV 139 ± 26 mmHg versus PLV 52 ± 11 mmHg; P O 2 , CMV 26 ± 15 mmHg versus PLV 184 ± 60 mmHg. In addition, there was a significant increase in dynamic compliance and a reduction in pulmonary hypertension. Nitric oxide was only efficacious in the PLV group, causing a further increase in oxygenation and a decrease in pulmonary hypertension. These effects were reversed when the nitric oxide was stopped. Conclusion: This study shows that PLV both improves gas exchange and pulmonary mechanics in CDH and allows the effective delivery of nitric oxide to reduce the pulmonary hypertension associated with CDH.

Inhalation exposure to JP-8 jet fuel alters pulmonary function and substance P levels in Fischer 344 rats.

In a simulated military flightline exposure protocol, Fischer 344 rats (F344) were used to investigate the pulmonary effects of JP-8 jet fuel inhalation. Exposures were nose only and for 1 h daily. Groups were exposed for 7 days (7D) or 28 days (28D). Each exposure group had a matched longitudinal control group (LC7 and LC28). Exposure concentrations of 520 mg m-3 caused an increase in dynamic compliance after 7 days of exposure, but compliance changes were not seen with continued exposure (28D, 495 mg m-3). Pulmonary resistance was increased in both 7- and 28-day JP-8-exposed groups. Changes in pulmonary function were accompanied by a decrease in substance P concentrations from the bronchoalveolar lavage fluid (BALF). No significant change was observed in BALF levels of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, which is a marker of endothelial cell function. The JP-8-exposed rats gained significantly less weight during the study period than the LC7 and LC28 groups, and the lungs of the 7D group were heavier by wet lung/body weight ratio (WtL/WtB). Alveolar clearance of technetium-labelled diethylenetriamine pentaacetate ([99mTc]DTPA) was increased in jet fuel-exposed groups. Light microscopy showed no pathological evidence of lung injury. Recovery from the early pulmonary effects of JP-8 inhalation occurred with continued exposure, as seen by recovery of pulmonary compliance and WtL/WtB.

Modulation of bronchial responsiveness in horses by phenylbutazone and furosemide

Summary Effects of phenylbutazone (pbz) and furosemide (fur) on the respiratory tract of horses were evaluated, focusing on bronchial responsiveness. Four healthy Thoroughbreds were used and data were analyzed by use of a Latin square design. Histamine provocation tests (0.5, 1, 2, and 4 µg/kg/min, iv) were done: (1) without prior treatment with pbz or fur, (2) 30 minutes after administration of pbz (8 mg/kg, iv), (3) 1 hour after administration of fur (1 mg/kg, iv), and (4) after administration of pbz plus fur. Pulmonary function tests (dynamic compliance, resistance, respiratory frequency, and tidal volume) and heart rate were monitored throughout the experiments. Phenylbutazone did not influence basal pulmonary function test results, whereas fur caused a significant (P &lt; 0.05) increase in dynamic compliance and decrease in resistance. Histamine infusion resulted in a dose-dependent decrease in dynamic compliance and a dose-dependent increase in resistance, respiratory frequency, and heart rate. Phenylbutazone administration significantly (P &lt; 0.05) attenuated most of the changes induced by histamine, whereas fur had less protective action. Administration of pbz plus fur before administration of histamine was less effective than administration of pbz alone.

Flunixin meglumine blocks frusemide‐induced bronchodilatation in horses with chronic obstructive pulmonary disease

Six horses that developed acute airway obstruction (heaves) when housed in a barn and fed poor-quality hay were studied. Airway obstruction was verified by a maximal change in pleural pressure during tidal breathing (delta Pplmax) of at least 15 cmH2O. Frusemide (1.0 mg/kg bwt) or an equivalent volume of vehicle was then administered intravenously (iv) and lung function was measured 15, 30, 60, 120, 180, 240 and 300 mins after drug administration. The effect of frusemide on lung function was also studied after treatment of horses with the cyclooxygenase inhibitor flunixin meglumine (1.1 mg/kg every 8 h for 2 days before the experiment). Frusemide significantly reduced the delta Pplmax beginning 15 mins after drug administration. This effect persisted for 5 h. The reduction in delta Pplmax was due partly to an increase in dynamic compliance and partly to a decrease in pulmonary resistance. Tidal volume and respiratory frequency were unaffected by frusemide. Vehicle had no effect on lung function. Flunixin meglumine abolished the effect of frusemide on airway calibre but did not prevent diuresis. These results indicate that the effect of frusemide on airways of horses with heaves persists for at least 5 h, is mediated through prostanoids, and is not a result of diuresis.

The effect of clenbuterol on lung function parameters in calves suffering from bronchopneumonia.

Pulmonary function testing was performed in calves affected with bronchopneumonia. In these calves respiratory rate, viscous work per litre air and per minute, intrapleural pressure difference, mean inspiratory and expiratory flow rate and ventilation per minute were significantly increased. Total resistance of the lung was just not significantly increased. Dynamic compliance and tidal volume were significantly reduced. The main effect of clenbuterol was a significant increase in dynamic compliance. The reduction in the total resistance of the lung was just not significant. These results indicate that clenbuterol can antagonise, at least partly, the alterations caused by bronchopneumonia.

Reversibility of airway obstruction in chronic obstructive lung disease.

The effect of intravenous aminophylline on pulmonary mechanics was investigated in 31 patients with chronic obstructive lung disease. Significant decrease in pulmonary resistance and early increase in dynamic compliance were characteristic of patients with asthma and bronchitis whereas in patients with emphysema change in resistance was insignificant and increase in dynamic compliance was delayed. Patients with bronchial asthma showed greater decrease in inspiratory resistance than patients with chronic bronchitis and greater decrease in both inspiratory and expiratory resistance than patients with chronic bronchitis and emphysema. Study of changes in pulmonary mechanics after a bronchodilator might be useful in distinguishing various types of chronic obstructive lung disease.