Biomedical subjects

A B Adams

Publications and source records attributed to A B Adams.

At least 19 recordsLinked to original sources

PubMed2006

Optimal phasic tracheal gas insufflation timing: an experimental and mathematical analysis.

OBJECTIVE: To investigate the modulation of CO2 clearance by changes in the duration of tracheal gas flow application during tracheal gas insufflation (TGI). DESIGN: Combination of bench studies using a commercial test lung and a commercially available intensive care ventilator and mathematical analysis using a clearance model derived from first principles. SETTING: University pulmonary research laboratory. PATIENTS: None. INTERVENTIONS: Experiments using TGI were performed on a test lung at two combinations of tidal volume and frequency. TGI was limited to part of the expiratory phase (the terminal 10-100% of expiration), and two different TGI catheter flow rates were studied. Permutations over a range of compliances, dead-space volumes, catheter flows, and TGI durations were collected. A mathematical model incorporating key ventilatory and TGI-related variables was developed to provide a first-principles theoretical foundation for interpreting the experimental results. MEASUREMENTS AND MAIN RESULTS: In the physical model, alveolar Pco2 attained a minimum value with TGI flow applied during the terminal 40-60% of the expiratory phase, a finding that was consistent over an almost eight-fold range of expiratory time constants. The mathematical model shows the same qualitative pattern as the experimental model, indicating that the observed behaviors are not an experimental artifact. CONCLUSION: The optimal duration of expiratory TGI flow application is stable over a wide range of impedance characteristics. Such stability suggests that near maximal effect of expiratory TGI could be obtained by applying TGI flow solely within the final 50% of the expiratory phase. Such uniform restriction of the application profile might both simplify technique implementation and decrease adverse consequences.

Carbon Dioxide↗

PubMed2006

NK cells mediate costimulation blockade-resistant rejection of allogeneic stem cells during nonmyeloablative transplantation.

Although T-cell CD28/CD40 costimulation blockade represents a powerful mechanism to promote immune tolerance during murine allotransplantation, it has not yet been successfully translated to clinical transplantation. We determined the impact of natural killer (NK) cells on costimulation blockade-resistant rejection of donor bone marrow. We found that NK cells represent a potent barrier to engraftment: host NK depletion led to increased donor stem cell survival, increased mixed hematopoietic chimerism and to engraftment of low doses of donor marrow (1 x 10(8)/kg) that were otherwise rejected. To understand the mechanisms of NK alloreactivity, we employed an in vivo NK-specific cytotoxicity assay. We found that an increased proportion of target cells were killed between days 2 and 8 after cell transfer, and that NK killing of parental targets was inducible: NK cells preprimed with allotargets were more efficient at their elimination upon reexposure. Finally, both transplant and in vivo NK-killing models were used to determine the contribution of LFA-1 to NK alloreactivity. Blockade of LFA-1 led to decreased NK-mediated killing, and increased alloengraftment. These results identify NK alloreactivity as an integral component to costimulation blockade-resistant rejection, and suggest that its inhibition may represent an important target in the clinical translation of tolerance-induction transplantation.

Animals↗

PubMed2005

Mathematical models for pressure controlled ventilation of oleic acid-injured pigs.

One-compartment, mathematical models for pressure controlled ventilation, incorporating volume dependent compliances, linear and nonlinear resistances, are constructed and compared with data obtained from healthy and (oleic acid) lung-injured pigs. Experimental data are used to find parameters in the mathematical models and were collected in two forms. Firstly, the P(e)-V curves for healthy and lung injured pigs were constructed; these data are used to compute compliance functions for each animal. Secondly, dynamic data from pressure controlled ventilation for a variety of applied pressures are used to estimate resistance parameters in the models. The models were then compared against the collected dynamic data. The best mathematical models are ones with compliance functions of the form C(V) = a + bV where a and b are constants obtained from the P(e)-V curves and the resistive pressures during inspiration change from a linear relation P(r) = RQ to a nonlinear relation P(r) = RQ(epsilon) where Q is the flow into the one-compartment lung and epsilon is a positive number. The form of the resistance terms in the mathematical models indicate the possible presence of gas-liquid foams in the experimental data.

Animals↗

PubMed2001

Characterization of virus-mediated inhibition of mixed chimerism and allospecific tolerance.

Simultaneous blockade of the CD28 and CD40 T cell costimulatory pathways has been shown to effectively promote skin allograft survival in mice. Furthermore, blockade of one or both of these pathways has played a central role in the development of strategies to induce mixed hematopoietic chimerism and allospecific tolerance. It has recently been observed that the beneficial effects of CD40 blockade and donor splenocytes in prolonging skin graft survival can be abrogated by some viral infections, including lymphocytic choriomeningitis virus (LCMV). In this study, we show that LCMV infection prevents prolonged allograft survival following CD28/CD40 combined blockade. We further show that LCMV prevents the induction of allospecific tolerance and mixed hematopoietic chimerism, while delay of infection for 3-4 wk posttransplant has no effect on tolerance induction. Because of reports of anti-H-2(d) activity following LCMV infection, we assayed the ability of LCMV-specific T cells to respond to alloantigen at a single cell level. Although we confirm that LCMV infection induces the generation of alloreactive cells, we also demonstrate that LCMV-specific T cells do not divide in response to alloantigen. The alloresponse suppressed by costimulation blockade is restored by LCMV infection and correlates with increased dendritic cell maturation. We hypothesize that the costimulation blockade-resistant rejection mediated by LCMV could be partly attributable to the up-regulation of alternative costimulatory pathways subsequent to LCMV-induced dendritic cell maturation.

Animals↗

PubMed2001

Application of tracheal gas insufflation to acute unilateral lung injury in an experimental model.

In unilateral lung injury, application of global positive end-expiratory pressure (PEEP) may cause overdistension of normal alveoli and redistribution of blood flow to diseased lung areas, thereby worsening oxygenation. We hypothesized that selective application of tracheal gas insufflation (TGI) will recruit the injured lung without causing overdistension of the normal lung. In eight anesthetized dogs, left lung saline lavage was performed until Pa(O(2))/FI(O(2)) fell below 100 mm Hg. Then, the dogs were reintubated with a Univent single lumen endotracheal tube that incorporates an internal catheter to provide TGI. After injury, increasing PEEP from 3 to 10 cm H(2)O did not change gas exchange, hemodynamics, or lung compliance. Selective TGI, while keeping end-expiratory lung volume (EELV) constant, improved Pa(O(2))/FI(O(2)) from 212 +/- 43 to 301 +/- 38 mm Hg (p < 0.01) while Pa(CO(2)) and airway pressures decreased (p < 0.01). During selective TGI, reducing tidal volume to 5.2 ml/kg while keeping EELV constant, normalized Pa(CO(2)), did not affect Pa(O(2))/FI(O(2)), and decreased end-inspiratory plateau pressure from 16.6 +/- 1.0 to 11.9 +/- 0.5 cm H(2)O (p < 0.01). In unilateral lung injury, we conclude that selective TGI (1) improves oxygenation at a lower pressure cost as compared with conventional mechanical ventilation, (2) allows reduction in tidal volume without a change in alveolar ventilation, and (3) may be a useful adjunct to limit ventilator-associated lung injury.

Animals↗

PubMed2001

Costimulation blockade, busulfan, and bone marrow promote titratable macrochimerism, induce transplantation tolerance, and correct genetic hemoglobinopathies with minimal myelosuppression.

Mixed hemopoietic chimerism has the potential to correct genetic hemological diseases (sickle cell anemia, thalassemia) and eliminate chronic immunosuppressive therapy following organ transplantation. To date, most strategies require either recipient conditioning (gamma-irradiation, depletion of the peripheral immune system) or administration of "mega" doses of bone marrow to facilitate reliable engraftment. Although encouraging, many issues remain that may restrict or prevent clinical application of such strategies. We describe an alternative, nonirradiation based strategy using a single dose of busulfan, costimulation blockade, and T cell-depleted donor bone marrow, which promotes titratable macrochimerism and a reshaping of the T cell repertoire. Chimeras exhibit robust donor-specific tolerance, evidenced by acceptance of fully allogeneic skin grafts and failure to generate donor-specific proliferative responses in an in vivo graft-versus-host disease model of alloreactivity. In this model, donor cell infusion and costimulation blockade without busulfan were insufficient for tolerance induction as donor-specific IFN-gamma-producing T cells re-emerged and skin grafts were rejected at approximately 100 days. When applied to a murine beta-thalassemia model, this approach allows for the normalization of hemologic parameters and replacement of the diseased red cell compartment. Such a protocol may allow for clinical application of mixed chimerism strategies in patients with end-stage organ disease or hemoglobinopathies.

Animals↗

PubMed2001

Conventional immunosuppression and co-stimulation blockade.

Organ transplantation has become an accepted and successful therapeutic intervention for many patients with end-stage organ disease. Current conventional immunosuppressive regimens achieve very good short-term allograft survival but long-term outcomes are less than adequate. Furthermore, non-specific immunosuppression has its attendant side-effects including increased risks of malignancy and infection as well as drug-specific sequellae. With recent advances in the field of immunology, promising new therapies have arisen that could potentially eliminate lifelong drug therapy and promote indefinite acceptance of the donor tissue. Identification of co-stimulatory signals essential for T-cell activation has provided exciting new possibilities for controlling the alloimmune response. The compatibility of these new agents with proven conventional therapeutics has yielded mixed results. When used in combination, their immunosuppressive properties appear synergistic. However, if the goal of therapy is sustained, specific T-cell hyporesponsiveness, many conventional agents antagonize the effects of co-stimulatory blockade in several immune tolerance models.

Abatacept↗

PubMed2001

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.

Animals↗

PubMed2001

Selective tracheal gas insufflation during partial liquid ventilation improves lung function in an animal model of unilateral acute lung injury.

OBJECTIVE: During unilateral lung injury, we hypothesized that we can improve global lung function by applying selective tracheal gas insufflation (TGI) and partial liquid ventilation (PLV) to the injured lung. DESIGN: Prospective, interventional animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Adult mixed-breed dogs. INTERVENTIONS: In six anesthetized dogs, left saline lung lavage was performed until PaO(2)/FiO(2) fell below 100 torr (13.3 kPa). The dogs were then reintubated with a Univent single-lumen endotracheal tube, which incorporates an internal catheter to provide TGI. In a consecutive manner, we studied 1) the application of 10 cm H(2)O of positive end-expiratory pressure (PEEP); 2) instillation of 10 mL/kg of perflubron (Liquivent) to the left lung at a PEEP level of 10 cm H(2)O (PLV+PEEP 10 initial); 3) application of selective TGI (PLV+TGI) while maintaining end-expiratory lung volume (EELV) constant; 4) PLV+TGI at reduced tidal volume (VT); and 5) PLV+PEEP 10 final. MEASUREMENTS AND MAIN RESULTS: Application of PLV+PEEP 10 initial did not change gas exchange, lung mechanics, or hemodynamics. PLV+TGI improved PaO(2)/FiO(2) from 189 +/- 13 torr (25.2 +/- 1.7 kPa) to 383 +/- 44 torr (51.1 +/- 5.9 kPa) (p <.01) and decreased PaCO(2) from 55 +/- 5 torr (7.3 +/- 0.7 kPa) to 30 +/- 2 torr (4.0 +/- 0.3 kPa) (p <.01). During ventilation with PLV+TGI, reducing VT from 15 mL/kg to 3.5 mL/kg while keeping EELV constant decreased PaO(2)/FiO(2) to 288 +/- 49 torr (38.4 +/- 6.5 kPa) (not significant) and normalized PaCO(2). At this stage, end-inspiratory plateau pressure decreased from 19.2 +/- 0.7 cm H(2)O to 13.6 +/- 0.7 cm H(2)O (p <.01). At PLV+PEEP 10 final, measurements returned to those observed at previous baseline stage (PLV+PEEP 10 initial). CONCLUSIONS: During unilateral lung injury, PLV with a moderate PEEP did not improve oxygenation, TGI superimposed on PLV improved gas exchange, and combination of TGI and PLV allowed a 77% reduction in VT without any adverse effect on PaCO(2).

Animals↗

PubMed2001

Dynamic behavior during noninvasive ventilation: chaotic support?

Acute noninvasive ventilation is generally applied via face mask, with modified pressure support used as the initial mode to assist ventilation. Although an adequate seal can usually be obtained, leaks frequently develop between the mask and the patient's face. This leakage presents a theoretical problem, since the inspiratory phase of pressure support terminates when flow falls to a predetermined fraction of peak inspiratory flow. To explore the issue of mask leakage and machine performance, we used a mathematical model to investigate the dynamic behavior of pressure-supported noninvasive ventilation, and confirmed the predicted behavior through use of a test lung. Our mathematical and laboratory analyses indicate that even when subject effort is unvarying, pressure-support ventilation applied in the presence of an inspiratory leak proximal to the airway opening can be accompanied by marked variations in duration of the inspiratory phase and in autoPEEP. The unstable behavior was observed in the simplest plausible mathematical models, and occurred at impedance values and ventilator settings that are clinically realistic.

Critical Care↗

PubMed2001

Catheters for tracheal gas insufflation.

As an adjunct to mechanical ventilation, tracheal gas insufflation (TGI) injects gas flow into the trachea to flush carbon dioxide (CO2) from the anatomical and mechanical dead space, but the addition of TGI flow from a catheter may cause problems related to increased flow velocity at the catheter tip. Forward momentum and turbulence beyond the tip oppose expiratory flow and may cause or increase intrinsic positive end-expiratory pressure. If the catheter is placed within the endotracheal tube (ETT), the catheter itself acts as a resistive element to exhalation. Effects of the catheter presence (contact on or whipping against the airway) or local rapid gas flow effects on the tracheal mucosa are possible. Thus far, TGI has been delivered through a range of catheter sizes and styles. Two general design modifications have been incorporated in TGI systems to address the possible problems: embedding the catheter flow channel within the ETT, and directing the TGI flow cephalad. The LaBrune-Boussignac tube was designed with 6 or 8 channels embedded within the ETT, from which TGI flow exits laterally within the ETT at 1.5 cm from its tip. This avoids the use of a catheter and thus avoids local traumatic effects. A reverse-thrust catheter has been designed to direct flow within a sheath around the catheter tip; flow exits cephalad from a gap between the sheath and the catheter shaft. As part of a proposed ventilatory mode (intratracheal pulmonary ventilation) the reverse-thrust catheter delivers the tidal breath and, additionally, flushes CO2 and accelerates secretion removal during exhalation. A reverse-flow design ETT has been developed with two channels, one for tidal volume delivery and the other for TGI flow. The TGI channel is relatively large and flow is directed cephalad by a nozzle at the catheter tip. A recently developed bidirectional catheter allows the option of delivering TGI flow cephalad, towards the lungs or in both directions. Unfortunately, to be convenient, the use of specially designed catheters or ETTs requires the anticipation of TGI use. A complete system for the safe and convenient use of TGI in ventilated patients is not as yet available, but concerns about the safety and convenience of TGI delivery have been addressed with recent advances in catheter/tube design.

Catheterization↗

PubMed2001

Static and dynamic pressure-volume curves reflect different aspects of respiratory system mechanics in experimental acute respiratory distress syndrome.

INTRODUCTION: A lower inflection point, an upper inflection (or deflection) point, and respiratory system compliance can be estimated from an inspiratory static pressure-volume (SPV) curve of the respiratory system. Such data are often used to guide selection of positive end-expiratory pressure (PEEP)/tidal volume combinations. Dynamic pressure-volume (DPV) curves obtained during tidal ventilation are effortlessly displayed on modern mechanical ventilator monitors and bear a theoretical but unproven relationship to the more labor-intensive SPV curves. OBJECTIVE: Attempting to relate the SPV and DPV curves, we assessed both curves under a range of conditions in a canine oleic acid lung injury model. METHODS: Five mongrel dogs were anesthetized, paralyzed, and monitored to assure a stable preparation. Acute lung injury was induced by infusing oleic acid. SPV curves were constructed by the super-syringe method. DPV curves were constructed for a range of PEEP and inspiratory constant flow settings while ventilating at a frequency of 15 breaths/min and tidal volume of 350 mL. Functional residual capacity at PEEP = 0 cm H2O was measured by helium dilution. The change in lung volume by PEEP at 8, 16, and 24 cm H2O was measured by respiratory inductance plethysmography. RESULTS: The slope of the second portion of the DPV curve did not parallel the corresponding slope of the SPV curve. The mean lower inflection point of the SPV curve was 13.2 cm H2O, whereas the lower inflection point of the DPV curve was related to the prevailing flow and PEEP settings. The absolute lung volume during the DPV recordings exceeded (p < 0.05) that anticipated from the SPV curves by (values are mean +/- SEM) 267 +/- 86 mL, 425 +/- 129 mL, and 494 +/- 129 mL at end expiration for PEEP = 8, 16, and 24 cm H2O, respectively. CONCLUSIONS: The contours of the SPV curve are not reflected by those of the DPV curve in this model of acute lung injury. Therefore, this study indicates that DPV curve should not be used to guide the selection of PEEP/tidal volume combinations. Furthermore, an increase in end-expiratory lung volume occurs during tidal ventilation that is not reflected by the classical SPV curve, suggesting a stable component of lung volume recruitment attributable to tidal ventilation, independent of PEEP.

Animals↗

PubMed2001

Effects of decreasing the frequency of ventilator circuit changes to every 7 days on the rate of ventilator-associated pneumonia in a Beijing hospital.

INTRODUCTION: We investigated whether decreasing ventilator circuit changes from every 2 days to every 7 days would impact ventilator-associated pneumonia rates at our institution. METHODS: All mechanically ventilated patients at Peking Union Medical College Hospital were studied over a 21 month period. From March 1998 to February 1999, ventilator circuits were changed every 2 days, and from June through December 1999, ventilator circuits were changed every 7 days. Nosocomial pneumonia was identified using the criteria of the Centers for Disease Control. RESULTS: In the 2-day-change group, there were 2,277 ventilator-patient days and 38 patients developed pneumonia, resulting in a pneumonia rate of 16.7 cases per 1,000 ventilator days. The 7-day-change group accumulated 972 ventilator days and 8 patients contracted pneumonia, resulting in a pneumonia rate of 8.2 cases per 1,000 ventilator days. The pneumonia rate was significantly lower in the 7-day-change group (p = 0.007). To standardize for seasonal variability, we compared results from the same seasonal time frames (June to December 1998 for the 2-day-change group, and June to December 1999 for the 7-day-change group), and obtained similar findings: during those periods, pneumonia rates were 24.2 cases per 1,000 ventilator days for the 2-day-change group and 8.9 cases per 1,000 ventilator days for the 7-day-change group (p = 0.001). CONCLUSIONS: A circuit change interval of 7 days had a lower risk of ventilator-associated pneumonia than a 2-day change interval. Therefore, ventilator circuits can be safely changed every 7 days in our setting.

Cross Infection↗

PubMed2000

Genetic characterization of strain differences in the ability to mediate CD40/CD28-independent rejection of skin allografts.

Simultaneous blockade of the CD40 and CD28 T cell costimulatory pathways effectively promotes skin allograft survival in C3H/HeJ mice, extending median survival times (MSTs) beyond 100 days. This strategy is markedly less effective in C57BL/6 mice, with MSTs ranging between 20 and 30 days. In this study, we investigate the underlying genetic causes of these distinct phenotypes. Using H-2 congenic mice, we show that the genetic basis for the varied responses between these two strains is independent of the H-2 locus and T cell precursor frequency. C57BL/6 mice treated with costimulation blockade are able to generate allospecific CTL- and IFN-gamma-producing T cells within 3-4 wk posttransplant, whereas mice with a C3H background generate neither CTL- nor IFN-gamma-producing cells. Thus, differences appear to be in the generation of the immune response and not T cell homing. Strain differences in costimulation blockade-induced hyporesponsiveness persist in the absence of CD4(+) T cells, implying a direct effect on CD8(+) T cells. We demonstrate that genetic differences are important in cells of hemopoietic origin and that the costimulation blockade-resistant phenotype is dominant. Analysis of BXH recombinant inbred strains indicates that multiple loci contribute to the phenotype, and that the blockade resistance loci are preliminarily linked to 17 markers on four chromosomes. We conclude that strain variation in allograft MSTs following CD40/CD28 blockade results from the ability of CD8(+) T cells in some strains to use alternative modes of costimulation to mount an effective alloresponse.

Abatacept↗

PubMed2000

Cutting edge: administration of anti-CD40 ligand and donor bone marrow leads to hemopoietic chimerism and donor-specific tolerance without cytoreductive conditioning.

Transplantation tolerance, defined as allograft acceptance by an immunocompetent recipient in the absence of long-term immunosuppression, has remained an elusive goal in clinical transplantation. Robust experimental tolerance induction strategies have in common methods to induce mixed hemopoietic chimerism. To date, however, chimerism induction across allogeneic barriers has required recipient conditioning with irradiation or cytoablative agents. In this paper we show that B6 recipients of fully allogeneic BALB/c skin grafts treated with repeated doses of donor bone marrow and anti-CD40 ligand (CD40L) develop durable (>300 days), readily detectable (6-12%) multilineage hemopoietic chimerism, indefinite allograft acceptance (>300 days), and donor-specific tolerance to secondary skin grafts. Analysis of the TCR repertoire of treated mice indicates that the underlying mechanisms of tolerance are in part mediated by deletion of donor-reactive T cells. These data demonstrate that durable hemopoietic chimerism and robust transplantation tolerance can be achieved without cytotoxic conditioning using a potentially clinically applicable regimen.

Animals↗

PubMed2000

Prone positioning attenuates and redistributes ventilator-induced lung injury in dogs.

BACKGROUND: We previously demonstrated a markedly dependent distribution of ventilator-induced lung injury in oleic acid-injured supine animals ventilated with large tidal volumes and positive end-expiratory pressure > or =10 cm H2O. Because pleural pressure distributes more uniformly in the prone position, we hypothesized that the extent of injury induced by purely mechanical forces applied to the lungs of normal animals might improve and that the distribution of injury might be altered with prone positioning. OBJECTIVE: To compare the extent and distribution of histologic changes and edema resulting from identical patterns of high end-inspiratory/low end-expiratory airway pressures in both supine and prone normal dogs. DESIGN/SETTING: We ventilated 10 normal dogs (5 prone, 5 supine) for 6 hrs with identical ventilatory patterns (a tidal volume that generated a peak transpulmonary pressure of 35 cm H2O when implemented in the supine position before randomization, positive end-expiratory pressure = 3 cm H2O). Ventilator-induced lung injury was assessed by gravimetric analysis and histologic grading. MEASUREMENTS AND MAIN RESULTS: Wet weight/dry weight ratios (WW/DW) and histologic scores were greater in the supine than the prone group (8.8+/-2.8 vs. 6.1+/-0.7; p = .01 and 1.4+/-0.3 vs. 1+/-0.3; p = .037, respectively). In the supine group, WW/DW and histologic scores were significantly greater in dependent than nondependent regions (9.4+/-1.9 vs. 6.7+/-0.9; p = .01 and 2.0+/-0.4 vs. 0.9+/-0.4; p = .043, respectively). In the prone group, WW/DW also was greater in dependent regions (6.7+/-1.1 vs. 5.8+/-0.5; p = .054), but no significant differences were found in histologic scores between dependent and nondependent regions (p = .42). CONCLUSION: In this model of lung injury induced solely by mechanical forces, the prone position resulted in a less severe and more homogeneous distribution of ventilator-induced lung injury. These results parallel those previously obtained in oleic acid-preinjured animals ventilated with higher positive end-expiratory pressure.

Airway Resistance↗

PubMed2000

Effects of decreased respiratory frequency on ventilator-induced lung injury.

To determine if decreased respiratory frequency (ventilatory rate) improves indices of lung damage, 17 sets of isolated, perfused rabbit lungs were ventilated with a peak static airway pressure of 30 cm H(2)O. All lungs were randomized to one of three frequency/peak pulmonary artery pressure combinations: F20P35 (n = 6): ventilatory frequency, 20 breaths/min, and peak pulmonary artery pressure, 35 mm Hg; F3P35 (n = 6), ventilatory frequency, 3 breaths/min, and peak pulmonary artery pressure of 35 mm Hg; or F20P20 (n = 5), ventilatory frequency, 20 breaths/min, and peak pulmonary artery pressure, 20 mm Hg. Mean airway pressure and tidal volume were matched between groups. Mean pulmonary artery pressure and vascular flow were matched between groups F20P35 and F3P35. The F20P35 group showed at least a 4.5-fold greater mean weight gain and a 3-fold greater mean incidence of perivascular hemorrhage than did the comparison groups, all p </= 0.05. F20P35 lungs also displayed more alveolar hemorrhage than did F20P20 lungs (p </= 0.05). We conclude that decreasing respiratory frequency can improve these indices of lung damage, and that limitation of peak pulmonary artery pressure and flow may diminish lung damage for a given ventilatory pattern.

Animals↗

PubMed2000

Recruitment maneuvers in three experimental models of acute lung injury. Effect on lung volume and gas exchange.

Recruitment maneuvers (RM), consisting of sustained inflations at high airway pressures, have been advocated as an adjunct to mechanical ventilation in acute respiratory distress syndrome (ARDS). We studied the effect of baseline ventilatory strategy and RM on end-expiratory lung volume (EELV) and oxygenation in 18 dogs, using three models of acute lung injury (ALI; n = 6 in each group): saline lavage (LAV), oleic acid injury (OAI), and intratracheal instillation of Escherichia coli (pneumonia; PNM). All three models exhibited similar degrees of lung injury. The PNM model was less responsive to positive end-expiratory pressure (PEEP) than was the LAV or OAI model. Only the LAV model showed an oxygenation response to increasing tidal volume (VT). After RM, there were transient increases in Pa(O(2)) and EELV when ventilating with PEEP = 10 cm H(2)O. At PEEP = 20 cm H(2)O the lungs were probably fully recruited, since the plateau airway pressures were relatively high ( approximately 45 cm H(2)O) and the oxygenation was similar to preinjury values, thus making the system unresponsive to RM. Sustained improvement in oxygenation after RM was seen in the LAV model when ventilating with PEEP = 10 cm H(2)O and VT = 15 ml/kg. Changes in EELV correlated with changes in Pa(O(2)) only in the OAI model with PEEP = 10 cm H(2)O. We conclude that responses to PEEP, VT, and RM differ among these models of ALI. RM may have a role in some patients with ARDS who are ventilated with low PEEP and low VT.

Animals↗