Elastic recoil pressure arising from surface tension in hamster lungs treated with intratracheal bleomycin

Lung elastic recoil pressure arising from surface tension (Ps) was evaluated in normal and bleomycin-treated lungs. Twenty two male golden hamsters were separated into a control group (group A, n = 10) and a bleomycin group (group B, n = 12). Group B was given a single intratracheal instillation of bleomycin and group A was given normal saline as a control. Thirty days after instillation, three cycles of static air -and saline-filled pressure-volume curves (P-V curve) were measured. Ps was graphically derived from air- and saline-filled P-V curves. The Ps of groups A and B were compared at the same lung volumes. Mean body weight and nose-to-tail length of the two groups did not differ significantly. Total lung capacity, defined as lung air volume at a transpulmonary pressure of 25 cmH2O, was significantly smaller in group B (mean +/- S.E. was 4.08 +/- 0.20 ml) than in group A (mean +/- S.E. was 5.23 +/- 0.12 ml) (p less than 0.01). The Ps of group B was significantly larger than that of group A at all lung volumes studied (p less than 0.01-0.05). These results indicate that the lung elastic recoil pressure component due to the surface tension was increased by intratracheal instillation of bleomycin in hamsters.     

The hazardous effects of alveolar hypocapnia on lung mechanics during weaning from cardiopulmonary bypass

The bronchoconstrictive effects of alveolar hypocapnia during weaning from cardiopulmonary bypass (CPB) were investigated in patients undergoing elective coronary artery revascularization. Thirty patients were randomly assigned into two equal groups. In both groups, mechanical ventilation was initiated for 3 min prior to weaning from CPB with the venous pressure low. This kept the pulmonary vascular bed empty, resulting in alveolar hypocapnia (ETCO2 < 2 kPa). Peak airway pressure (P(peak)) and plateau pressures (P(plateau)) were recorded. In group 1, 5% CO2 was added to the inspiratory gas mixture and the ETCO2 allowed to rise (ETCO2 > 3.3 kPa). The ventilation pressure measurements were recorded again after 3 min stabilization. In group 2, the venous pressure was increased to allow the pulmonary venous bed to fill and the ventilation pressures recorded after a 3 min period of stabilization. In group 1, the ventilatory pressures dropped significantly (p < 0.001) when the alveolar hypocapnia was reversed with added CO2 (P(peak) 19.71 +/- 5.7 to 12.31 +/- 2.8 cmH2O and P(plateau) 13.15 +/- 3.28 to 9.15 +/- 2.23 cmH2O). In group 2, a similar effect was achieved by allowing filling of the pulmonary vascular bed (P(peak) 17.46 +/- 4.72 to 11.92 +/- 3.03 cmH2O and P(plateau) 13.93 +/- 4.10 to 9.37 +/- 3.00 cmH2O). These results suggest that filling the pulmonary vascular bed prior to initiating ventilation, when weaning from CPB, prevents the otherwise deleterious effects of alveolar hypocapnia, resulting in raised bronchomotor tonus and raised airway pressures.     

Left ventricular stiffness and chamber geometry in the pressure-overloaded hypertrophied heart.

Pressure-overloaded hypertrophy of the left ventricle (LV) was produced by coarctation of the ascending aorta in 7 dogs. The overall mean weight of the left ventricle (LVW) was 7.86 +/- 1.49 (S.D.) g/kg body weight; (normal, 5.99 +/- 0.70 g/kg: p less than 0.05). After potassium arrest, pressure-volume (P-V) relationships were examined with the left ventricles isolated from the normals and from the dogs of left ventricular hypertrophy (LVH-dogs). In both groups, the P-V relationships could be expressed by an equation deltaV=a-be-cP throughout the range of filling pressure of 2.5 to 35 cmH2O, where deltav was the actual volume change of LV, P intraventricular pressure, and a, b and c constants. A sensitive index of LV stiffness, the half-inflation pressure (h), was defined as 1n (2b/a)/c. In hypertrophied hearts, h was 10.5 +/- 0.7 cmH2O; (normal 8.0 +/- 0.4 cmH2O; P less than 0.001). The ratio of LVW to LVVp=h (the left ventricular volume at h) in hypertrophy, which was related to the LV chamber geometry, was 3.1 +/- 0.6 in contrast with the normal value of 2.0 +/- 0.3. The development of concentric hypertrophy was thus demonstrated. Moreover, h was closely correlated with LVW/LVVp=h in both the normals and the LVH-dogs (r=0.83; p less than 0.01). On the other hand, an index of LV wall stiffness h/LVW/LVVP=h was relatively constant. Therefore, the increase of LV stiffness in the LVH-dogs was attributed to the change in chamber geometry.     

Perfluorocarbon-associated gas exchange

BACKGROUND AND METHODS: Liquid ventilation with oxygenated perfluorocarbon eliminates surface tension due to pulmonary air/fluid interfaces, and improves pulmonary function and gas exchange in surfactant deficiency. In liquid ventilation, perfluorocarbon is oxygenated, purged of CO2, and cycled into and out of the lungs using an investigational device. A new approach, perfluorocarbon-associated gas exchange, uses a conventional ventilator and combines features of liquid ventilation and continuous positive-pressure breathing. In 13 normal piglets, a volume of perfluorocarbon equivalent to the normal functional residual capacity (30 mL/kg) was instilled into the trachea, left in situ, and volume-regulated gas ventilation (FIO2 1.0) was resumed. For 1 hr, perfluorocarbon was continuously bubble-oxygenated within the lungs, where it directly participated in gas exchange. RESULTS: PaO2 and PaCO2 averaged 401 +/- 51 and 40 +/- 4 torr (53.6 +/- 6.8 and 5.3 +/- 0.5 kPa), respectively. Peak airway pressure during perfluorocarbon-associated gas exchange (22 +/- 2 cm H2O at 1 hr) and during continuous, positive-pressure breathing (23 +/- 4 cm H2O) were nearly identical. Venous oxygen saturation and pH were normal (73 +/- 8% and 7.43 +/- 0.05, respectively, at 1 hr). CONCLUSIONS: Perfluorocarbon-associated gas exchange was uniformly well tolerated, and its efficiency approached that of continuous positive-pressure breathing. Applications of perfluorocarbon technology to lung disease may not be limited by existing instrumentation.     

Delayed fetal pulmonary maturation in a rabbit model of the diabetic pregnancy.

A rabbit model for the diabetic pregnancy was used to investigate the etiology of delayed pulmonary maturation observed in infants of diabetic mothers. Pregnant rabbit does were made glucose intolerant and insulinopenic by injection of alloxan, a pancreatic beta-cell cytotoxin. At 28 d (term approximately 31 d) fetuses of these animals were hyperglycemic, but were not hyperinsulinemic and did not demonstrate tissue overgrowth. Fetal pulmonary maturity was assessed by measurement of pressure-volume relationships on the fetal lungs. Fetuses of glucose-intolerant does demonstrated less retention of air on deflation. Phospholipid components of pulmonary surfactant were assayed on fluid obtained from lavage of the fetal lungs. Levels of disaturated phosphatidylcholine (per-cent total-lavage phospholipids) were diminished in fetuses of glucose-intolerant does compared to control fetuses (20.5 +/- 4.2 vs. 38.0 +/ 4.3%; P less than 0.01). Lecithin/sphingomyelin ratios were similar in both groups and phosphatidylglycerol was not detected in either group. There was a direct correlation between the percentage of alveolar disaturated phosphatidylcholine and retention of air on lung deflation. These findings suggest that in this model pulmonary instability was a result of diminished alveolar disaturated phosphatidylcholine, and this diminution did not result from fetal hyperinsulinemia.     

Independent lung ventilation in patients with unilateral pulmonary contusion. Monitoring with compliance and EtCO2

OBJECTIVE: a) to describe a non-barotraumatic ventilatory setting for independent lung ventilation (ILV); b) to determine the utility of single lung end-tidal CO(2) (EtCO(2)) monitoring to evaluate the ventilation to perfusion (V/Q) matching in each lung during ILV and for ILV weaning. DESIGN: prospective study. SETTING: general intensive care unit in a university teaching hospital. PATIENTS: twelve patients with unilateral thoracic trauma needing ILV. INTERVENTIONS AND RESULTS: ILV was started with each lung ventilated with the same tidal volume (Vt): plateau airway pressure (Pplat) was 34.2+/-3.2 cmH2O in diseased lungs (DL) and 18.1+/-1.9 cmH2O in normal lungs (NL) ( P<0.01). Static compliance (Cst) was 9.9+/-1.1 ml/cmH(2)O in DL and 19.3+/-1.7 ml/cmH(2)O in NL ( P<0.01). EtCO2 was 22.5+/-2.2 mmHg in DL and 36.6+/-1.9 mmHg in NL ( P<0.01). PaO(2)/FiO(2) was at 151+/-20. PEEP was applied on the DL and each lung was ventilated with a Vt that developed Pplat < or =26 cmH2O. With this setting, Vt given to the NL was unchanged, whereas it was reduced in the DL (238+/-30 ml vs 350+/-31 ml; P<0.01). Cst and EtCO2 were still significantly lower in the DL ( P<0.01, respectively), while the PaO(2)/FiO(2) ratio remained unchanged. Vt was then progressively increased in the DL as Pplat decreased, but remained unchanged in the NL. ILV was discontinued when Vt, Cst and EtCO(2) were the same in each lung. PaO(2)/FiO(2) ratio had then increased to 295+/-18. CONCLUSIONS: a) during ILV, adequate oxygenation and a reduction in V/Q mismatch can be obtained by setting Vt and PEEP to keep Pplat below a safe threshold for barotrauma; b) measurement of single lung EtCO2 can be useful to evaluate progressive V/Q matching.     

Effects of partial liquid ventilation on regional pulmonary blood flow distribution of isolated rabbit lungs

OBJECTIVE: Partial liquid ventilation with perfluorocarbons may increase alveolar hydrostatic transmural pressure and may result in a redistribution of pulmonary blood flow from dependent to nondependent lung regions. To test this hypothesis under controlled study conditions, we determined intrapulmonary blood flow distributions during gas and perfluorocarbon ventilation in isolated rabbit lungs. DESIGN: Controlled animal study with an ex vivo isolated lung preparation. SETTING: Research laboratory for Experimental Anesthesiology at the Heinrich-Heine-University of Düsseldorf. SUBJECTS: New Zealand White rabbits. INTERVENTIONS: The lungs were perfused with autologous blood at constant flow (150 mL/min) and ventilated with 5% C(O2) in air (positive end-expiratory pressure, 2 cm H2O; tidal volume, 10 mL/kg body weight; respiratory rate, 30 breaths/ min) without and with perfluorocarbon administered intratracheally (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: Regional lung perfusion was measured with colored microspheres in apical, central, peripheral, and basal samples before and after bronchial instillation of perfluorocarbons. Compared with gas ventilation, intrapulmonary blood flow during perfluorocarbon ventilation was higher in apical samples (49.4+/-8.6 mL/min/g vs. 38.3+/-6.8 mL/min/g dry weight; p = .03) and lower in basal samples (22.2+/-5.1 mL/min/g vs. 39.9+/-8.2 mL/min/g; p = .04). CONCLUSIONS: Our findings suggest that during partial liquid ventilation, intrapulmonary blood flow is redistributed toward less-dependent lung regions. (Crit Care Med 2000; 28:1522-1525) KEY WORDS: partial liquid ventilation; perfluorocarbons; isolated rabbit lungs; pulmonary circulation; regional blood-flow distribution; colored microspheres     

Relative roles of vascular and airspace pressures in ventilator-induced lung injury

OBJECTIVE: To determine whether elevations in pulmonary vascular pressure induced by mechanical ventilation are more injurious than elevations of pulmonary vascular pressure of similar magnitude occurring in the absence of mechanical ventilation. DESIGN: Prospective comparative laboratory investigation. SETTING: University research laboratory. SUBJECTS: Male New Zealand white rabbits. INTERVENTIONS: Three groups of isolated, perfused rabbit lungs were exposed to cyclic elevation of pulmonary artery pressures arising from either intermittent positive pressure mechanical ventilation or from pulsatile perfusion of lungs held motionless by continuous positive airway pressure. Peak, mean, and nadir pulmonary artery pressures and mean airway pressure were matched between groups (35, 27.4 +/- 0.74, and 20.8 +/- 1.5 mm Hg, and 17.7 +/- 0.22 cm H2O, respectively). MEASUREMENTS AND MAIN RESULTS: Lungs exposed to elevated pulmonary artery pressures attributable to intermittent positive pressure mechanical ventilation formed more edema (6.8 +/- 1.3 vs. 1.1 +/- 0.9 g/g of lung), displayed more perivascular (61 +/- 26 vs. 15 +/- 13 vessels) and alveolar hemorrhage (76 +/- 11% vs. 26 +/- 18% of alveoli), and underwent larger fractional declines in static compliance (88 +/- 4.4% vs. 48 +/- 25.1% decline) than lungs exposed to similar peak and mean pulmonary artery pressures in the absence of tidal positive pressure ventilation. CONCLUSIONS: Isolated phasic elevations of pulmonary artery pressure may cause less damage than those occurring during intermittent positive pressure mechanical ventilation, suggesting that cyclic changes in perivascular pressure surrounding extra-alveolar vessels may be important in the genesis of ventilator-induced lung injury.     

Experimental results of using the "open lung concept"

Several elements of the "open lung concept", like ventilation with small tidal volumes, were incorporated into various ventilatory strategies. Our study demonstrates how the whole concept can be applied in an animal model using a standardized protocol with the following possible results. Eighteen pigs weighing between 30 and 45 kg were anaesthetized, tracheotomized and ventilated. Acute lung injury was induced by surfactant washout. Blood gases were monitored via a continuous arterial sensor system (Trendcare system). After washout, the ventilatory pattern of the American "ARDS Network study" was applied (PEEP = 9 cmH2O, volume controlled mode with a tidal volume of 6 ml/kg body weight and a respiratory rate of 25 breaths per minute). Afterwards, the opening pressure and the pressure at which the lung collapses were titrated. Both levels were used as the basis for adjusting the recruitment pressure and PEEP, which was necessary to keep the lung open. The respiratory rate was chosen in such a way that at a low intrapulmonary pressure difference between inspiration and expiration as well as normocapnia was reached. After induction of an acute lung injury by surfactant washout, the oxygenation index (OI) dropped from 556 +/- 54 to 176 +/- 89 mmHg. In the "ARDS Network" mode, OI increased to 285 +/- 49 mmHg. After alveolar recruitment with a peak pressure of 53 +/- 7 cmH2O and application of a median PEEP of 17 +/- 3 cmH2O, oxygenation returned close to baseline. A pCO2 of 33 +/- 4 mmHg resulted after using a respiratory rate of 39 breaths per minute. The median tidal volume was 8 ml/kg body weight. Despite a short arterial systolic blood pressure drop of 23 +/- 11 mmHg during recruitment, no significant difference was detectable afterwards compared to the baseline. Using low tidal volumes alone, complete reopening was not achieved in an experimentally induced acute lung injury. After recruitment manoeuvres, it was possible to reopen the lung and keep it open by application of a sufficient PEEP.     

Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung

OBJECTIVE: To test the hypothesis that the lung injury induced by certain mechanical ventilation strategies is associated with changes in the pulmonary surfactant system. DESIGN: Analysis of the pulmonary surfactant system from isolated rat lungs after one of four different ventilatory strategies. SETTING: A research laboratory at a university. SUBJECTS: A total of 45 Sprague-Dawley rats. INTERVENTIONS: Isolated lungs were randomized to either no ventilation (0-TIME) or to ventilation at 40 breaths/min in a humidified 37 degrees C chamber for either 30 mins or 120 mins with one of the following four strategies: a) control (CON, 7 mL/kg, 3 cm H2O positive end-expiratory pressure); b) medium volume, zero end-expiratory pressure (MVZP, 15 mL/kg, 0 cm H2O end-expiratory pressure); c) medium volume, high positive end-expiratory pressure (MVHP, 15 mL/kg, 9 cm H2O positive end-expiratory pressure); and d) high volume, zero end-expiratory pressure (HVZP, 40 mL/kg, 0 cm H2O end-expiratory pressure). MEASUREMENTS: Pressure-volume curves were determined before and after the ventilation period, after which the lungs were lavaged for surfactant analysis. MAIN RESULTS: Compared with 0-TIME, 30 mins of ventilation with the HVZP strategy or 120 mins of ventilation with CON and MVZP strategies caused a significant decrease in compliance. Groups showing a decreased compliance had significant increases in the amount of surfactant, surfactant large aggregates, and total lavage protein compared with 0-TIME. CONCLUSIONS: A short period of injurious mechanical ventilation can cause a decrease in lung compliance that is associated with a large influx of proteins into the alveolar space and with alterations of the pulmonary surfactant system. The changes of surfactant in these experiments are different from those seen in acute lung injury, indicating that they may represent an initial response to mechanical ventilation.     

Changes in Sedimentation of Surfactant in Ventilated Excised Rat Lungs: PHYSICAL ALTERATIONS IN SURFACTANT ASSOCIATED WITH THE DEVELOPMENT AND REVERSAL OF ATELECTASIS

We ventilated excised rat lungs at a constant tidal volume (CTV); they developed areas of atelectasis which could be reversed by a large inflation (CTV + I) or prevented by the addition of positive end-expiratory pressure to the CTV. To explore the possibility that these modes of ventilation led to changes in surfactant, we lavaged the lungs and centrifuged the returns at 500 g; we measured the amount of disaturated phosphatidylcholine (DSPC) in the resultant pellet and supernatant fluid as a marker for surfactant. We found 16.9+/-1.5 (mean+/-SE), 38.0+/-2.4, 18.3+/-1.6, and 21.7+/-2.3% of the total lavage DSPC, in the pellet from freshly excised, CTV, CTV + I, and positive end-expiratory pressure to the CTV lungs, respectively. The total amount of lavage DSPC was the same in all groups.The ultrastructure of acellular material pelleted by sequential centrifugation of lavage returns at 500, 1,000, and 60,000 g was examined. We found mostly tubular myelin in the 500-g and 1,000-g pellets, but no tubular myelin in the 60,000-g pellet.Air inflation pressure-volume measurements from the degassed state revealed that the opening pressure and recoil pressures up to 75% of total lung capacity were significantly higher in the CTV than in the CTV + I lungs. There were no differences between these groups in air deflation or in saline inflation and deflation pressure-volume measurements. Our findings suggest that CTV leads to increases in the tubular myelin form of surfactant and that this leads to increased surface tension in alveoli which results in alveolar collapse.     

Gene therapy of surfactant protein B deficiency

Surfactant protein B (SP-B) is encoded by a single gene, and the mature protein is expressed by alveolar type II epithelial (ATII) cells of the lungs. Studies in transgenic mice and its hereditary deficiency in humans have established its indispensable role in postnatal survival. An established gene therapy regime for treating SP-B deficiency could overcome the limitations of surfactant replacement therapies or lung transplantation. Among the various viral and non-viral gene delivery tools available, only adenoviral vectors have been tested for delivering SP-B cDNA to the lungs of animal models. This review discusses the various vectors that are available for delivering therapeutic genes into ATII cells.     

Mask mechanics and leak dynamics during noninvasive pressure support ventilation: a bench study

OBJECTIVE: To study the mask mechanics and air leak dynamics during noninvasive pressure support ventilation. SETTING: Laboratory of a university hospital. DESIGN: A facial mask was connected to a mannequin head that was part of a mechanical respiratory system model. The mask fit pressure (P(mask-fit)) measured inside the mask's pneumatic cushion was adjusted to 25 cmH(2)O using elastic straps. Pressure support (PS) was set to ensure a maximal tidal volume distal to the mask (VT(distal)) but avoiding failure to cycle to exhalation. MEASUREMENTS: Airway pressure (P(aw)), P(mask-fit), mask occlusion pressure (P(mask-occl)=P(mask-fit)-P(aw)), VT proximal (VT(prox)), distal to the mask (VT(distal)), air leak volume ( Leak=VT(prox)-VT(distal)), and inspiratory air leak flow rate (difference between inspiratory flow proximal and distal to the mask) were recorded. RESULTS: PS 15 cmH(2)O was the highest level that could be used without failure to cycle to exhalation (VT(distal) of 585+/-4 ml, leak of 32+/-1 ml or 5.2+/-0.2% of VT(prox), and a minimum P(mask-occl) of 1.7+/-0.1 cmH(2)O). During PS 16 cmH(2)O the P(mask-occl) dropped to 1.1+/-0.1 cmH(2)O, and at this point all flow delivered by the ventilator leaked around the mask, preventing the inspiratory flow delivered by the ventilator from reaching the expiratory trigger threshold. CONCLUSION: P(mask-fit) and P(mask-occl) can be easily measured in pneumatic cushioned masks and the data obtained may be useful to guide mask fit and inspiratory pressure set during noninvasive positive pressure ventilation.     

Oxygenation index,an indicator of optimal distending pressure during high-frequency oscillatory ventilation?

OBJECTIVE: To test the hypothesis that, during high-frequency oscillatory ventilation (HFOV) of pigs with acute lung injury, the oxygenation index (OI = Paw*FIO(2)*100/PaO(2)) is minimal at the lowest continuous distending pressure (Paw), where the physiological shunt fraction is below 0.1 (Paw(optimal)). DESIGN AND SETTING: Prospective, observational study in a university research laboratory. SUBJECTS: Eight Yorkshire pigs weighing 12.0+/-0.5 kg, with lung injury induced by lung lavage. INTERVENTIONS: After initiation of HFOV, the pigs were subjected to a stepwise increase of Paw to obtain under-inflation, optimal inflation and over-distension of the lungs (inflation) in series, followed by a similar decrease of Paw (deflation). MEASUREMENTS AND RESULTS: At each Paw level, the OI and physiological shunt fraction were determined. The OI reached a minimum of 6.2+/-1.4 at Paw 30+/-4 cmH(2)O during inflation and a minimum of 2.4+/-0.3 at Paw 13+/-2 cmH(2)O during deflation. Paw(optimal) was 32+/-6 cmH(2)O on the inflation limb and 14+/-2 cmH(2)O on the deflation limb. The difference between the Paw at minimal OI and Paw(optimal) was -1.9+/-4.2 cmH(2)O (NS) during inflation and -1.5+/-1.6 cmH(2)O (p<0.05) during deflation. In 15 out of the 16 comparisons, the difference in Paw was within one step (+/-3 cmH(2)O). CONCLUSION: The minimal OI is indicative for the Paw where oxygenation is optimal during HFOV in surfactant-depleted pigs.     

"Ideal PEEP" is superior to high dose partial liquid ventilation with low PEEP in experimental acute lung injury

OBJECTIVE: To determine the effects of a high dose partial liquid ventilation (PLV) approximating the amount of the functional residual capacity (FRC) with low levels of positive end-expiratory pressure (PEEP) compared to a lung-protective strategy with volume-controlled mechanical ventilation (vcMV) with a PEEP level above the lower inflection point (LIP) on pulmonary gas exchange, haemodynamics, respiratory mechanics and lung injury in an experimental model of acute lung injury (ALI). DESIGN: Prospective, randomised, controlled study. METHODS: Twenty-four anaesthetised, tracheotomised and mechanically ventilated (FIO(2) 1.0) pigs underwent induction of ALI by repeated saline wash-out of surfactant. Animals were randomly assigned to receive either PLV ( PLV, n=8) with 30 ml/kg of perfluorocarbons (PF 5080, 3 M, Germany) and a PEEP level of 5 cmH(2)O, to receive vcMV with a PEEP level of 1 cmH(2)O above the LIP ( (ideal) PEEP, n=8), or to receive vcMV with a PEEP level of 5 cmH(2)O ( Controls, n=8). MEASUREMENTS AND RESULTS: Measurements of pulmonary gas exchange, respiratory mechanics and haemodynamics were performed hourly for a 6 h period. In the (ideal) PEEP group, intra-pulmonary shunt (Qs/Qt) decreased from 55+/-5% after induction of ALI to 10+/-3% ( p<0.05 versus Controls and versus PLV) and PaO(2) increased from 52+/-4 to 566+/-19 mmHg after 6 h of treatment ( p<0.05 versus Controls and versus PLV). In the PLV group, Qs/Qt decreased from 50+/-5% after induction of ALI to 24+/-3% ( p<0.05 versus Controls) and PaO(2) increased from 59+/-5 to 306+/-35 mmHg after 6 h of treatment ( p<0.05 versus Controls). In the PLV group and in Controls, mean pulmonary artery pressure (MPAP) was significantly increased from 27+/-2 to 38+/-2 mmHg and from 29+/-1 to 40+/-1 mmHg, respectively, 6 h after induction of ALI ( p<0.05 versus (ideal) PEEP), while in the (ideal) PEEP group, MPAP was maintained between 26+/-1 and 31+/-2 mmHg for 6 h after ALI. Cardiac output (CO) decreased significantly in the (ideal) PEEP group compared to Controls ( p<0.05), while CO did not change in the PLV group and in Controls. The compliance of the respiratory system (C(RS)) increased in the (ideal) PEEP group after induction of ALI from 11+/-2 to 22+/-5 ml/mbar ( p<0.05 versus Controls and versus PLV) and in the PLV group from 10+/-2 to 13+/-3 ml/mbar after 6 h of treatment ( p<0.05 versus Controls). On histological examination, the highest total injury scores were found in animals of the PLV group ( p<0.05 versus Controls and versus (ideal) PEEP), while the lowest total lung injury score was found in the dependent lung regions of the (ideal) PEEP group ( p<0.05 versus Controls). CONCLUSION: In this porcine model of ALI, vcMV with a PEEP level of 1 cmH(2)O above the LIP was superior to high dose PLV with a PEEP of 5 cmH(2)O in improving gas exchange and lung mechanics. In terms of lung damage, the treatment in the (ideal) PEEP group resulted in the lowest total lung injury scores.     

Correlation between alveolar recruitment /derecruitment and inflection points on the pressure-volume curve

Objective To determine whether individual alveolar recruitment/derecruitment (R/D) is correlated with the lower and upper inflections points on the inflation and deflation limb of the whole-lung pressure-volume (P-V) curve. Design and setting Prospective experimental study in an animal research laboratory. Subjects Five anesthetized rats subjected to saline-lavage lung injury. Interventions Subpleural alveoli were filmed continuously using an in vivo microscope during the generation of a whole-lung P-V curve using the super syringe technique. Alveolar R/D was correlated to the calculated inflection points on both limbs of the P-V curve. Measurements and results There was continual alveolar recruitment along the entire inflation limb in all animals. There was some correlation (R ² = 0.898) between the pressure below which microscopic derecruitment was observed and the upper inflection point on the deflation limb. No correlation was observed between this pressure and the lower inflection point on the inflation limb. Conclusions In this physiological experiment in lungs with pure surfactant deactivation we found that individual alveolar recruitment measured by direct visualization was not correlated with the lower inflection point on inflation whereas alveolar derecruitment was correlated with alveolar derecruitment on deflation. These data suggest that inflection points on the P-V curve do not always represent a change in alveolar number. This article is discussed in the editorial available at: .     

Influence of intratracheal application of fluorocarbon 72 and different lipid-mixtures on mechanical behavior of isolated immature pig lungs.

Substitution of surfactant in immature lungs has two functional targets: the reduction of the overall alveolar surface tension and the mechanical stabilization of the system of alveoli having different diameters. Indeed, the lowering of the surface tension facilitates the inflation of the lungs, but according to Laplace's law small and large alveoli are not in pressure equilibrium as long as the surface tension is equal in both small and large alveoli. In the present work, we tried to stabilize the lungs and to compare the effect of bolus surfactant substitution with the two-step substitution of fluorocarbons and surfactant. In all, 24 fetal immature lungs were used. For our experiments we used fluorocarbon 72 (FC-72) with a surface tension of 12 mN/m. In groups 1 and 2, a mixture of dipalmitoylphosphatidylcholine (DPPC): cholesterol 9:1 (molar ratio) or DPPC: phosphatidylglycerol (PG) 9:1 (molar ratio) was administered intratracheally as a bolus. In the case of groups 3 and 4, the immature lungs were rinsed first with FC-72. After removing the fluorocarbon, the lungs were artificially ventilated and the DPPC: cholesterol 9:1 (group 3) or DPPC:PG 9:1 mixture (group 4) was given in aerosol form. Static pressure-volume curves (p-v) of the mean values of the 6 lungs in each group were registered at the beginning (0 min) and after 20 and 40 min of artificial ventilation. Airway opening pressure, weight-specific end-inspiratory lung compliance, and phospholipid contents were investigated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nasal continuous positive airway pressure (NCPAP) on breathing pattern in spontaneously breathing premature newborn infants

OBJECTIVE: The aim of the study was to assess the influence of nasal continuous positive airway pressure (NCPAP) on breathing pattern in preterm newborns. DESIGN: Prospective study. SETTING: Neonatal intensive care unit. PATIENTS: Ten premature newborn infants on NCPAP (gestational age range from 27 to 32 weeks, mean birth weight 1300+/-460 g) admitted in our neonatal intensive care unit (NICU) for respiratory distress syndrome. METHODS: Breathing patterns and changes in lung volumes level were obtained using respiratory inductive plethysmography (RIP), at random CPAP levels (0, 2, 4, 6 and 8 cmH2O). Raw data were analysed for end-expiratory lung volume level (EELV-level), tidal volume (Vt), respiratory rate, phase angle and labour breathing index (LBI). RESULTS: CPAP increased EELV-level by 2.1+/-0.3xVt from 0 to 8 cmH2O ( p<0.01). Vt increased by 43% from CPAP of 0 cmH2O to CPAP of 8 cmH2O ( p<0.01). We also found that CPAP lowered the phase angle (from 76+/-21 degrees at CPAP of 0 cmH2O to 30+/-15 degrees at CPAP of 8 cmH2O; p<0.01 ) and LBI (from 1.7+/-0.8 at CPAP of 0 cmH2O to 1.2+/-0.3 at CPAP of 8 cmH2O; p<0.05). CONCLUSION: NCPAP improves the breathing strategy of premature infants with respiratory failure, as reflected by improved thoraco-abdominal synchrony, increased Vt and reduction of the LBI. This effect is associated with an increase in EELV-level with CPAP level. However, further investigations are necessary to establish the best CPAP level that ensures both safety and efficiency.     

Effects of beta-2 agonist on tracheal fluid flow, surfactant and pulmonary mechanics in the fetal lamb

To study the effects of beta-2 agonist on tracheal fluid, surfactant and pulmonary mechanics in fetal lamb lung, ritodrine hydrochloride, a preferential beta-2 agonist, was infused i.v. at a rate of 1.3 +/- 0.4 micrograms/kg/min (mean +/- S.D.) for 24 hr into six twin chronically catheterized fetal lambs starting between 0.86 and 0.91 gestation. Ritodrine infusion was associated with statistically significant metabolic and pulmonary effects in comparison with twin controls. Fetal serum glucose levels were elevated 1.7-fold, arterial blood pH fell 0.04 U and arterial blood pO2 fell 5.1 torr in the ritodrine-infused twins. Tracheal fluid flow was reduced 6.9-fold and surface active material flux into the tracheal fluid was thereby virtually eliminated. But the surface active material content of tracheal fluid and lung lavage increased 3.0-fold. The surfactant phospholipid content of lung lavage also increased 3.0-fold with no change in its composition. There was a concomitant improvement in pulmonary mechanics on pressure-volume curves: the lungs of the ritodrine-infused twins filled with 1.7-fold more air on inflation to 40 cm of water pressure and also retained 1.7-fold more air on deflation to 10 cm of water pressure. We conclude that beta-2 agonist inhibits tracheal fluid flow, increases surfactant in lung lavage and improves lung stability in the fetal lamb lung. We speculate that preferential beta-2 adrenergic stimulation of the fetal lung with ritodrine could be helpful in the prevention of neonatal respiratory distress syndrome because of enhanced surfactant availability in airways and improved pulmonary mechanics.     

Influence of respiratory rate on gas trapping during low volume ventilation of patients with acute lung injury

OBJECTIVE: Reduction in tidal volume (Vt) associated with increase in respiratory rate to limit hypercapnia is now proposed in patients with acute lung injury (ALI). The aim of this study was to test whether a high respiratory rate induces significant intrinsic positive end-expiratory pressure (PEEPi) in these patients. DESIGN: Prospective crossover study. SETTING: A medical intensive care unit. INTERVENTIONS AND MEASUREMENTS: Ten consecutive patients fulfilling criteria for severe ALI were ventilated with a 6 ml/kg Vt, a total PEEP level at 13+/-3 cmH(2)O and a plateau pressure kept at 23+/-4 cmH(2)O. The respiratory rate was randomly set below 20 breaths/min (17+/-3 breaths/min) and increased to 30 breaths/min (30+/-3 breaths/min) to compensate for hypercapnia. External PEEP was adjusted to keep the total PEEP and the plateau pressure constant. PEEPi was computed as the difference between total PEEP and external PEEP. The lung volume retained by PEEPi was then measured. RESULTS: Increase in respiratory rate resulted in significantly higher PEEPi (1.3+/-0.4 versus 3.9+/-1.1 cmH(2)O, p<0.01) and trapped volume (70+/-43 versus 244+/-127 ml, p<0.01). External PEEP needed to be reduced from 11.9+/-3.4 to 9.7+/-2.9 cmH(2)O ( p<0.01). PaO(2) was not affected but the alveolar-arterial oxygen tension difference slightly worsened with the high respiratory rate (p<0.05). CONCLUSIONS: An increase in respiratory rate used to avoid Vt reduction-induced hypercapnia may induce substantial gas trapping and PEEPi in patients with ALI.