Lung-thorax Compliance Research Articles

Nebulized corticosteroid improves pulmonary function and outcome in experimental porcine septicemia

Nebulized beclomethasone dipropionate was administered to six anesthetized and artificially ventilated pigs at 6-hourly intervals after infusion of live S. aureus (aerosol group). Changes in pulmonary mechanics, gas exchange and hemodynamics during an observation period of 44 h were compared with those in six pigs subjected to the same insults but given no corticosteroid (non-treatment group). Six pigs served as controls, without sepsis or aerosol, but with the same general management (control group). The septic insult induced an acute 3-fold increase in mean pulmonary artery pressure (MPAP) in the aerosol and non-treatment group. MPAP fell to near baseline levels in the aerosol group, but remained significantly higher in the non-treatment group. Mean systemic arterial pressure fell more in the non-treatment than in the aerosol group, reaching its lowest level at 32 h. Pulmonary function was less affected in the aerosol group, with significantly better maintenance of arterial oxygenation, lower venous admixture and superior lung-thorax compliance than in the non-treatment group. Survival was significantly improved in the aerosol group. In this porcine model of septicemia-induced adult respiratory distress syndrome, nebulized corticosteroid thus attenuated the development of respiratory failure.

Experimental Neonatal Respiratory Failure Induced by a Monoclonal Antibody to the Hydrophobic Surfactant-Associated Protein SP-B

The present experiments were designed to test whether selective blocking of the surfactant-associated hydrophobic polypeptide SP-B (8.7 kD) would interfere with lung function during neonatal adaptation. A MAb to porcine SP-B was produced by hybridoma cell line (8B5E); this antibody cross-reacts with rabbit SP-B. Six mg of MAb to SP-B, dissolved in 0.2 mL of saline, was instilled into the airways of near-term newborn rabbits (gestational age 29 d), before the onset of ventilation. Control animals received the same amount of nonspecific rabbit IgG in saline, or were untreated. The animals were ventilated for 120 min with a standardized tidal volume (10 mL/kg). The specific antibody caused a prominent, immediate decrease in lung-thorax compliance, associated with acute inflammatory and exudative lung lesions including hyaline membranes. IgG alone had no such effects. Our data suggest that the MAb to SP-B inhibits surfactant function in the neonatal period by blocking one of the mechanisms responsible for fast adsorption of the surfactant phospholipids to the alveolar air-liquid interface. In addition, an acute inflammatory reaction is probably triggered in the lung parenchyma by the immune reaction.

Application of a new ventilator-multi-plethysmograph system for testing efficacy of surfactant replacement in newborn rabbits

We applied a new ventilator-multi-plethysmograph system to evaluate the effect of surfactant replacement in newborn rabbits under well controlled, nearly physiological conditions characterized by normal ECG and adequate PCO2 in right ventricular heart blood obtained at the end of the experiment. Up to 10 animals were ventilated in parallel with a pressure-constant common respirator system. Using a working pressure of 4.9 kPa (50 cmH2O), we could adjust the pressure delivered to each animal within the range of 0.49-4.4 kPa (5-45 cmH2O), by changing the length of an open high-resistance tube constituting the outflow limb of the connection between the common ventilator tube and the tracheal cannula. Immature newborn animals obtained after 27.5 days gestation and ventilated for 30 min with a tidal volume of 8-10 ml.kg-1 had a mean +/- SD lung-thorax compliance of 4.2 +/- 1.1 ml.kPa-1.kg-1 (0.41 +/- 0.11 ml.cmH2O-1.kg-1) and PCO2 of 8.5 +/- 1.9 kPa. In littermates treated at birth with a large dose of natural surfactant (Curosurf, 200 mg.kg-1, compliance increased to 6.0 +/- 1.0 ml.kPa-1.kg-1 (0.68 +/- 0.10 ml.cmH2O-1.kg-1) (p less than 0.01) and PCO2 decreased to 6.9 +/- 1.2 kPa (p less than 0.01). Near-term animals, obtained at 30 days gestation and ventilated under similar conditions had a compliance of 7.2 +/- 0.9 ml.kPa-1.kg-1 (0.71 +/- 0.09 ml.cmH2O-1.kg-1) and PCO2 of 6.4 (1.2) kPa. Administration of surfactant (same dose as above) to these mature animals at birth had no adverse effects.

Influence of Glottic Mechanism on Pulmonary Function after Acute Lung Injury

We measured arterial gas tensions, respiratory timing, and intratracheal pressure in 12 rabbits to investigate the consequences of translaryngeal intubation with normal and subsequently injured lungs. Data were collected before, during, and after intubation. Intubation in normal rabbits precipitated no untoward effects on gas exchange or respiratory phase timing. However, there was significant elevation of subglottic pressure during expiration following extubation. Central venous injection of oleic acid (0.08 ml/kg) induced an acute lung injury that after 24 h was characterized by reduced PaO2 and dynamic lung-thorax compliance and tachypnea. Intubation in animals with acute lung injury was associated with a significant decline in arterial oxygenation, tachypnea, and increased PCO2. Expiratory tracheal pressure and expiratory time were greater and PaCO2 and respiratory rate were lower following extubation. We conclude that translaryngeal intubation following acute lung injury exacerbates already compromised pulmonary function by preventing a compensatory expiratory braking maneuver by the glottic apparatus.

Tracheobronchial dilating effect of high frequency jet ventilation.

Effect of high frequency jet ventilation (HJFV) on tracheobronchial tone was examined in anesthetized dogs. Changes in intraluminal pressure of water-filled endotracheal cuff (Pcuff) were used as an indicator of tracheal smooth muscle tone. Animals were initially ventilated with conventional mechanical ventilation (CMV) to maintain normal Pa(CO)(2). HFJV (2.0 Hz.) was then applied to each animal in such a way to maintain the same mean airway pressure and Pa(CO)(2) as in CMV. Immediately after changing CMV to HFJV, Pcuff decreased significantly and remained decreased during the period of HFJV. After changing HFJV to CMV, Pcuff gradually returned to its previous level. Histamine-induced tracheobronchial constriction was partially released by HFJV as shown by a decrease in Pcuff and airway resistance (Raw) and by an increase in static lung-thorax compliance (Cst) measured immediately after the cessation of HFJV. These results suggest that HFJV has a tracheobronchial dilating action, presumably mediated by pulmonary stretch reflex, and this may be one of the mechanisms of an increase in mucous secretion and of other reported favorable effects of HFJV in some types of respiratory failure.

LUNG FUNCTION IN THE SUPINE AND LATERAL DECUBITUS POSITIONS IN ANAESTHETIZED INFANTS AND CHILDREN

We have measured dynamic lung compliance or static lung thorax compliance, functional residual capacity (FRC), and two indices of pulmonary gas mixing (pulmonary clearance delay (PCD) and single breath alveolar mixing efficiency (SBAME)) in 25 children in the supine and lateral decubitus position during nitrous oxide-halothane anaesthesia. Fifteen children (5 month-8 yr) breathed spontaneously and 10 (4 month-9 yr) underwent mechanical ventilation. Tidal volume and rate of ventilation were, respectively, 3.5-6.6 ml kg-1 and 22-46 b.p.m. in spontaneously breathing supine children, and 8.3-15 ml kg-1 and 20-30 b.p.m. in mechanically ventilated supine children, and did not differ significantly in the lateral position. There was no significant change in compliance when the child was turned to the lateral position, but FRC increased from 22 (SD7) to 25 (8) ml kg-1 (P less than 0.01) in the spontaneously breathing group and from 19 (6) to 24 (8) ml kg-1 (P less than 0.01) in the other group. In spontaneously breathing children, PCD and SBAME indicated a somewhat impaired pulmonary gas mixing (P less than 0.05) after the child had been turned to the lateral position, but no change occurred in the other group. These findings suggest that the distribution of ventilation in anaesthetized children in the lateral position is similar to that reported previously in anaesthetized adults.

Inositol and glucocorticoid in the development of lung stability in male and female rabbit fetuses.

Inasmuch as inositol affects the development of lung surfactant, and exogenous glucocorticoids accelerate fetal lung maturation, a possible interaction of the two substances on alveolar stability of preterm rabbit fetuses of 28 days gestation was investigated. On days 26 and 27 of gestation inositol or glucose were added to the diet of does treated with betamethasone (0.2 mg/kg intramuscularly on days 26 and 27). Inositol increased lung-thorax compliance of paralyzed fetuses at all insufflation pressures studied (from 16 to 22.5 and 30 cm H2O and back to 22.5, and 16 cm H2O). At a ventilation pressure of 30 cm H2O, lung-thorax compliance of fetuses treated with inositol plus betamethasone was more than doubled as compared with controls (1.2 +/- 0.6 versus 0.5 +/- 0.2 ml/kg x cm H2O; p less than 0.001). Inositol alone had no detectable effect on compliance, whereas betamethasone tended to increase compliance (p = 0.05). According to variance analysis, the effect of inositol was statistically significant only among the males. Inositol prevented the glucocorticoid-induced decrease in lung protein and, to a lesser extent, the decrease in DNA. Inositol did not further increase the lavageable surfactant pool of the glucocorticoid-treated, ventilated fetuses, although the area occupied by lamellar bodies within type II cells was increased after inositol plus betamethasone. According to the present study, inositol modifies the physiologic and biochemical response of the immature fetal lung to a pharmacologic dose of exogenous glucocorticoid.

Noninvasive Monitoring of Lung Function During Mechanical Ventilation

Noninvasive monitoring can greatly enhance decision-making and clinical approaches to the respiratory failure patient. Newer microprocessor systems will calculate, present, and trend derived data such as airway resistance and lung-thorax compliance. These changes characterize the degree of lung dysfunction and parallel abnormalities in gas exchange.

Hemodynamics and intrathoracic pressure transmission during controlled mechanical ventilation and positive end-expiratory pressure in normal and low compliant lungs.

PEEP can significantly reduce cardiac output. This reduction in cardiac output is frequently attributed to transmission of airway pressure to intrathoracic vascular structures. We designed an acute lung injury (ALI) model in swine (n = 7) characterized by low lung thorax compliance (CLT) and compared the fractional transmission of airway pressure to pleura (PPL) and pericardium (PPC) and hemodynamics to normal animals (n = 5) during controlled mechanical ventilation (CMV) and PEEP. Fractional transmission of PEEP to PPL and PPC was reduced significantly from 62 +/- 8% and 54 +/- 19 (SD)% to 34 +/- 7% and 36 +/- 9% in normal and ALI animals, respectively. End-inspiration tracheal pressure was significantly higher in the low compliant group; thus, cardiac output was equally depressed in both groups despite reduction in fractional airway pressure transmission in ALI animals, possibly because absolute inspiratory PPL and PPC were similar due to increased pressure required to inflate injured lungs. The results of this investigation do not support the presumption that low CLT blunts hemodynamic consequences of CMV and PEEP.

Respiratory failure in mice caused by a hybridoma making antibodies to the 15 kDa surfactant apoprotein.

Hybridoma cells were obtained by fusing spleen cells from mice, immunized against the 15 kDa porcine surfactant apoprotein, with a myeloma cell line. Adult mice were inoculated intraperitoneally with this hybridoma; mice that were not inoculated or were inoculated with myeloma cells served as controls. Lung-thorax compliance was measured at various intervals after inoculation. The animals were then killed for histologic-morphometric evaluation of alveolar air expansion, inflammatory reaction in the pulmonary parenchyma, and intraalveolar edema. In the hybridoma group, the mice developed respiratory failure 9 days after inoculation, with markedly reduced lung-thorax compliance, lung congestion, alveolar collapse, hemorrhagic pulmonary edema, and hyaline membranes. Morphometric data from the same animals showed reduced volume density of alveolar air, and increased volume densities of intraalveolar "fluid" (edema) and tissue components. These lung lesions are similar to those in the adult respiratory distress syndrome.

Prolonged ventilation of the premature newborn rabbit after treatment with natural or apoprotein-based artificial surfactant.

Premature rabbit neonates (gestational age 27 days) were treated at birth with natural surfactant purified from chloroform extracts of porcine lung lipids either by acetone precipitation (Surfactant CK, n = 10) or liquid gel chromatography (Curosurf, n = 22). Another group of animals received artificial surfactant "reconstituted" from isolated low molecular weight (less than or equal to 15 K) apoproteins and synthetic dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) (Aposurf, n = 10). The phospholipid concentrations of the preparations were adjusted to provide the same individual dose of DPPC for each group of treated animals (3 or 4 mg). In comparison with untreated controls from the same litters, there was a 4-7-fold enhancement of lung-thorax compliance in all groups of surfactant-treated animals during a 3-h period of artificial ventilation. The average initial (20 min) compliance value was lower in the Aposurf-treated group than in animals receiving natural surfactant preparations, but the difference between the groups gradually diminished and was no longer statistically significant during the 2nd and 3rd h of artificial ventilation. Judged from the fall in tidal volume during ventilation with a short expiration phase (0.17 instead of 0.75 s), the apoprotein-based artificial surfactant was also less effective in stabilizing the lungs. A similar conclusion could be drawn from data on alveolar expansion in histological sections, evaluated by automated image analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory failure caused by intratracheal saline: additive effect of xanthine oxidase.

Administration of physiological saline or drugs together with saline into the airways is becoming common clinical practice. However, there are few studies on possible side effects. We have studied the effects of saline, saline plus xanthine oxidase, and saline plus xanthine oxidase plus superoxidase dismutase on lung-thorax compliance and on arterial blood gases in anesthetized, paralyzed guinea pigs, ventilated for 2.5 h. Saline bolus (2-3 ml isotonic saline/kg body weight) into the airways reduced the compliance within 20 min to a mean of 39% of the pretreatment levels, and necessitated as increase in the respirator pressure. Saline plus xanthine oxidase decreased the compliance to 16% of the pretreatment levels. The xanthine oxidase-induced (but not saline-induced) decrease in lung compliance was relieved by superoxide dismutase. According to the present results xanthine oxidase induces a lung injury possible by production of free oxygen radicals. Superoxide dismutase can be valuable in prevention of free oxygen radical-mediated lung damage. Saline alone can be harmful when applied to the airways. This should be considered in clinical trials and in clinical practice.

Pressure control to accommodate patient breathing efforts during volume ventilation.

Intermittent positive-pressure ventilation is used to support patients whose unassisted breathing is inadequate. Mechanical ventilators deliver pressurized gas to the patient's lungs by using a pattern of volume and timing that is preset by the clinician. A weakness of existing control methods is their emphasis on maintaining adequate gas exchange while poorly accommodating the patient's efforts to reassume control of the delivery pattern. A method is proposed to control airway pressure within a breath by making it respond to measurements of volume. This method using pressure as a function of volume, or P(V) method, permits the patient to have transient control over flow rate and delivered volume. In addition, an adaptive controller is included that modifies the applied pressure during subsequent breaths; it assures an average flow rate and delivered volume at the levels prescribed by the clinician, when sustained changes occur in airway resistance, lung-thorax compliance, or breathing efforts. Analyses and computer simulations suggest that the P(V) method will be better than conventional volume ventilation in accommodating, within a breath, transient breathing efforts without long-term degradation of the prescribed delivery pattern. The P(V) method can restore the delivery pattern, using the adaptive controller, within a few breaths after changes occur in the patient's lung mechanics. We conclude that the P(V) method is feasible, that it may represent an improved method of patient ventilation, particularly during fighting or weaning from the ventilator, and that it warrants further investigation.

Acute and chronic effects of xanthine oxidase on lung thorax-compliance in guinea pigs.

Xanthine oxidase was given intratracheally in a single dose to guinea pigs. Lung compliance was measured after 4 h and 14 days respectively. Lung-thorax compliance was significantly lower compared with saline-treated controls both 4 h and 14 days after application of fluid. At 14 days there was a dose-related response between lung-thorax compliance and xanthine oxidase administered in the range 0-1.0 U. Superoxide dismutase (SOD) had a protective effect on xanthine oxidase action at 4 h, but not after 14 days. We suggest that the decreased lung-thorax compliance was caused by superoxide radicals, produced by the hypoxanthine-xanthine oxidase system, damaging lung tissue. We speculate that free oxygen radicals produced by the hypoxanthine-xanthine oxidase system could be an important contributory pathogenetic factor in producing both acute and chronic lung damage in, for instance, premature babies or adults, with respiratory distress syndrome.

Changes in Lung Volume and Lung-Thorax Compliance during Cardiac Surgery in Children 11 Days to 4 Years of Age

To examine the effects of cardiac surgery and cardiopulmonary bypass (CPB) on the lung, functional residual capacity (FRC) and lung-thorax compliance were measured at four stages during open heart surgery in 15 children. The patients were anesthetized with fentanyl/droperidol and N2O/O2, paralyzed, and ventilated with volume-controlled mechanical ventilation at 20-30 breaths/min. FRC was measured by tracer gas washout. Static lung-thorax compliance (CLT) was calculated as tidal volume divided by the airway pressure difference between the end of the postinspiratory pause and the end of the expiration, and also from the increase in FRC caused by adding 5 cmH2O of PEEP (CLT[FRC]). Before skin incision, both FRC and compliance were closely correlated with weight and length. During this stage, FRC was 21 +/- 5 ml/kg, CLT 0.90 +/- 0.21, and CLT(FRC) 1.28 +/- 0.35 ml X cmH2O-1 X kg-1 X PEEP 5 increased FRC by 34 +/- 9%. In patients with intact pleural cavities throughout the operation (n = 10), FRC increased by 4 +/- 2 ml/kg when the sternum was retracted (P less than 0.01). During CPB, FRC decreased by 4 +/- 3 ml/kg (P less than 0.01), and FRC at the end of surgery was 5 +/- 4 ml/kg less than before skin incision (P less than 0.01). In these ten children, there was a 13% and 6% decrease in mean CLT and CLT(FRC), respectively, during the operation (P less than 0.05) and mean CLT(FRC) was at least 40% greater than CLT during all four stages (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Capnography and the Bain circuit I: A computer model.

The Mapleson D anesthesia breathing system has no valves and allows rebreathing of carbon dioxide. Its coaxial version is known as the Bain system. The interpretation of capnograms obtained during its use requires an understanding of the interrelationships of patient and system variables. Toward that end, a systematic description of mechanical ventilation with the Bain circuit was undertaken based on the physical laws of gas transport. The mathematical formulation of the model contains the relations between pressure, flow, and volume in the tube, alveolar space, and ventilator. The flows, calculated from these relations, are used to determine the CO2 concentrations in the different parts of the model. Two sets of data are used--patient and system. The patient data, used to solve the equations numerically, are lung-thorax compliance, CO2 inflow into alveolar space (CO2 production), functional residual capacity, dead space volume, airway resistance, and respiratory quotient. The ventilation system data comprise the dimensions and volumes of the Bain circuit, ventilator, connectors, and tubes; spill valve pressure; resistances to flow in the individual tube parts; ventilator settings; and fresh-gas flow rates. After incorporation of a volunteer's respiratory variables into the model, capnograms obtained from the model compared well with those obtained from the volunteer. The structure of the model is such that it permits easy introduction or changes of patient and system variables to obtain individual results or model specific circumstances. This flexibility makes it a useful tool for understanding the properties of the Bain circuit under a variety of clinical circumstances. The results may be displayed in a number of different ways.

Effects of artificial ventilation on surfactant phospholipid metabolism in rabbits.

Surfactant phospholipid metabolism and lung stability were studied in mechanically ventilated and in spontaneously breathing rabbits (control group). During ventilation the dynamic lung-thorax compliance decreased to 79% after 6 h. Static compliance and amount and composition of surfactant phospholipids remained unaltered. These data indicate inactivation of alveolar surfactant during ventilation, which is reversible by a single large inflation. Incorporation of injected radioactively labeled palmitate into saturated phosphatidylcholine (SPC) of the lamellar body fraction increased significantly in the ventilated group; maximal specific activity increased from 20 dpm/nmol SPC at 6 h in the control group to 30 dpm/nmol SPC at 2 h in the ventilated group. The clearance of radioactivity from the lamellar bodies into the alveolar lumen was greatly enhanced in the ventilated group. The results are explained by assuming that as a result of the inactivation of alveolar surfactant, endocytosed surfactant is degraded in the type II cells instead of being recycled and that the degradation products are subsequently reutilized in surfactant synthesis. This interpretation is supported by computer simulations.

DOSE DEPENDANT EFFECTS OF SURFACTANT ON LUNG MECHANICS

Although exogenous surfactant replacement was proven to improve lung mechanics in clinical HMD (Fujiwara et.al. TA), optimal concentration and dose were not known. We studied the effect of different concentrations and quantity of TA in premature rabbits before first breath. Group A was treated with fixed lipid quantity, but variable TA concentration. Group B was treated with fixed concentration, but variable lipid quantity. We measured P-V curve (P-V) and lung-thorax compliance (CL) at 5 mg/ml to 40 mg/ml of concentration and 25 μg to 400 μg of quantity. Group A P-V curve data is given below. (Mean ± S.E.). In Group A, when lipid quantity was kept constant the variable concentration 10 mg/ml to 40 mg/ml of TA did not change the P-V curve and the CL. However when concentration of TA dropped to 5 mg/ml, the P-V curve and the CL changed adversely (p<0.02). Group B P-V curve and CL improved to maximum at 800 μg irrespective of concentrations. Further, the lipid quantity of 800 μg to 4000 μg had no further beneficial or adverse effect. We conclude 10 to 40 mg/ml of TA concentration,and lipid quanity of 800 μg to 4000 μg will have optimal effect on P-V curve and CL when instilled before the first breath.(*P5=5 cmH20 distending pr.).

Improved lung-thorax compliance in the premature rabbit neonate after treatment with dibuturyladenosine-3':5'-cyclic monophosphate.

Premature rabbit neonates, delivered on day 28 of gestation, were treated with a single dose of dibuturyladenosine-3':5'-cyclic monophosphate (cyclic AMP), 300 mg/kg, immediately after delivery, saline-injected litter-mates serving as controls. All animals were kept in body plethysmographs and ventilated artificially with 100% oxygen for 1 h, with a maximal tidal volume of 10 ml/kg body weight. Lung-thorax compliance was significantly improved in animals treated with cyclic AMP, both 30 and 60 min after onset of ventilation (0.92 +/- 0.09 vs. 0.59 +/- 0.08 ml/cm H2O.kg and 0.96 +/- 0.09 vs. 0.53 +/- 0.08, p less than 0.005), but there was no improvement in alveolar air expansion, evaluated histologically. Phosphatidylglycerol was absent in alveolar wash from all control animals, but present in 3 of the 8 pooled samples from the animals treated with cyclic AMP; this difference was not statistically significant, however.

Lung expansion in premature newborn rabbits treated with emulsified synthetic surfactant; principles for experimental evaluation of synthetic substitutes for pulmonary surfactant.

This paper presents a sequence of tests for experimental evaluation of potential substitutes for pulmonary surfactant. Differential thermal analysis and the pulsating bubble technique were applied to identify an emulsified mixture of synthetic lipids with properties similar to those of natural surfactant. Instilled into the airways of premature newborn rabbits, this emulsion improved pulmonary pressure-volume characteristics and enhanced lung-thorax compliance during artificial ventilation. However, the in vivo effect was inferior to that of natural surfactant, especially as the emulsion failed to prevent the development of bronchiolar epithelial lesions.