Biomedical subjects

Marla R Wolfson

Publications and source records attributed to Marla R Wolfson.

At least 19 recordsLinked to original sources

PubMed2007

Effects of recombinant Clara cell secretory protein (rhCC10) on inflammatory-related matrix metalloproteinase activity in a preterm lamb model of neonatal respiratory distress.

OBJECTIVE: To test the hypothesis that recombinant Clara cell secretory protein (rhCC10) instillation would foster improved lung function, acute structural preservation, and attenuation of matrix metalloproteinase (MMP) activity in a surfactant-deficient, mechanically ventilated lung. DESIGN: Interventional laboratory study. SETTING: An academic medical research facility in the northeastern United States. SUBJECTS: Sedated, ventilated premature lambs. INTERVENTIONS: Preterm lambs (n = 18; 126 +/- 3 days gestation) were instrumented, ventilated, and treated with 100 mg/kg exogenous surfactant. Lambs were randomized to receive 0, 0.5, or 5.0 mg/kg rhCC10 (n = 6 per group) and were ventilated for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Posttreatment, lung function and cardiopulmonary stability were monitored for the ventilation period and then animals were killed for in vitro surfactant function analysis, lung histomorphometry, and analysis of MMP-2, -7, and -9 as well as their tissue inhibitors (TIMP)-1 and -2. Ventilation efficiency and pulmonary compliance were improved in the 5.0-mg/kg rhCC10 group by 4 hrs. Lung expansion was variable in the apical regions only. MMP-2 quantity was greater in the apical than the base lung regions of rhCC10-treated groups, and rhCC10 decreased MMP-7 in the base of the lung. CONCLUSIONS: These data suggest that improved lung function in the surfactant-treated preterm lamb following intratracheal rhCC10 may be related to the reduction of proteolytic activity of MMP-7.

Animals↗

PubMed2006

Perfluorochemical liquids enhance delivery of superoxide dismutase to the lungs of juvenile rabbits.

Previous studies suggest acute lung injury (ALI) in premature newborns is associated with relative deficiency of antioxidant enzymes that may be ameliorated by recombinant human superoxide dismutase (rhSOD). Perfluorochemicals (PFCs) are distributed homogeneously and support gas exchange in diseased lungs. We investigated whether PFCs could provide an effective delivery system for rhSOD. Juvenile rabbits were lung-lavaged, treated with surfactant, and randomized: group I: fluorescently labeled rhSOD (5 mg/kg in 2 mL/kg saline); group II: fluorescently labeled rhSOD (5 mg/kg in 18 mL/kg PFC). Animals were ventilated with oxygen for 4 h; the lungs were harvested for analysis of SOD distribution and oxidative injury. Cardiopulmonary indices remained stable and similar between groups. Qualitative assessment (QA) showed a more homogeneous lung SOD distribution in group II and a better histologic profile. QA of lung SOD distribution showed significant increase in SOD concentrations in group II (7.37 +/- 1.54 microg/mg protein) compared with group I (1.65 +/- 0.23 microg/mg protein). Oxidative injury as assessed by normalized protein carbonyl was 149.1 +/- 26.8% SEM in group II compared with 200.5 +/- 7.3% SEM in group I. Plasma SOD was significantly higher in group II. Administration of rhSOD with or without PFCs does not compromise cardiovascular function or impede lung recovery after ALI. PFCs enhance rhSOD delivery to the lungs by 400% while decreasing lung oxidative damage by 25% compared with rhSOD alone. These data suggest that PFCs optimize lung rhSOD delivery and might enhance the beneficial effects of rhSOD in preventing acute and chronic lung injury.

Animals↗

PubMed2006

The impact of mechanical ventilation on immature airway smooth muscle: functional, structural, histological, and molecular correlates.

Preterm infants exposed to mechanical ventilation often develop airway dysfunction and bronchopulmonary dysplasia. The mechanisms of mechanical ventilation-induced airway injury are currently unknown. This study correlates the age-related effects of mechanical ventilation on airway function with structural alterations at the tissue, cellular, ultrastructural, and molecular levels. Mechanically ventilated and nonventilated tracheal rings were obtained from premature and newborn lambs. In tissue baths, the passive and active length-tension relationships and dose-response characteristics of the tracheal rings were determined. Fixed tracheal rings were digested and the resulting isolated smooth muscle cells measured. Rings were analyzed by light and electron microscopy. Additionally, protein was extracted from the tracheal smooth muscle and myosin heavy chain isoforms were separated by SDS-polyacrylamide gel electrophoresis and analyzed by densitometry. Mechanical ventilation resulted in a significant decrease of both the slope of the passive length-stress relationship and of maximal force generation, with both effects being most pronounced in the newborn age group. These age-related functional alterations correlated with a decrease in smooth muscle cell length and a disruption of ultrastructural architecture, which were also most pronounced in the older groups. Furthermore, mechanical ventilation resulted in epithelial denudation at all ages. There were no acute statistically significant effects of mechanical ventilation on myosin heavy chain isoform expression. This study demonstrates age-related effects of mechanical ventilation on the passive and active characteristics of tracheal function and provides a structural analysis of potential mechanisms. The mechanisms behind these functional differences involve ultrastructural changes in cell length, tissue matrix, and disruption of epithelial integrity. These findings help elucidate the pathogenesis of ventilator-induced airway injury.

Acetylcholine↗

PubMed2006

Effects of perfluorochemical evaporative properties on oxygenation during partial liquid ventilation.

BACKGROUND: The physical-chemical properties of perfluorochemical (PFC) liquids have been shown to influence physiological and cellular responses during partial liquid ventilation (PLV). The aim of this study is to compare the relationship between patho-physiological endpoints and the physical properties of three PFC liquids used in treating acute lung injury. METHODS: A total of 18 juvenile rabbits were randomized into conventional mechanical ventilation or PLV groups after lung saline lavages. Three PFC liquids, including Flutec perfluoro-1,3,5-trimethylcyclohexane (PP4; vapor pressure, 28.8 mmHg at 37 degrees C), Perfluorodecalin (PFD; vapor pressure, 13.6 mmHg at 37 degrees C), and Perflubron (PFB; vapor pressure, 10.4 mmHg at 37 degrees C) were used for PLV with no replacement for 4 h. A thermal detector was used to measure PFC loss rate. Physiological measurements and evaporative loss rate of PFC were done every 30 min, and lung histology was examined. RESULTS: The mean evaporative loss rate was significantly higher in the PP4 group (4.75 +/- 0.24 mL/kg per h) than in either the PFD (1.43 +/- 0.11 mL/kg per h) or the PFB (1.18 +/- 0.05 mL/kg per h) group (P < 0.05). The oxygenation of PFD and PFB was maintained good for 4 h, however, the PP4 group showed a fast deterioration since 2 h post-treatment due to fast dropping of the residual PP4 amount in lungs. Histology showed good alveolar integrity in the PFD and PFB groups. CONCLUSIONS: The effects of PLV are directly influenced by the evaporative property of the PFC liquid. With no replacement over 4 h, PLV effects could be maintained with utilizing a PFC liquid with low, rather than high, vapor pressure. PFC with high vapor pressure has a high loss rate and low residual volume that causes poor maintenance on oxygenation during PLV. Therefore, measuring PFC loss rate is important in future studies and clinical application of PLV.

Algorithms↗

PubMed2005

Effects of an intratracheally delivered anti-inflammatory protein (rhCC10) on physiological and lung structural indices in a juvenile model of acute lung injury.

BACKGROUND: Mechanical ventilation results in acute lung trauma that can stimulate processes that alter lung development. Activation of matrix metalloproteinases (MMPs) and their tissue-produced inhibitors (TIMPs) is initiated by the inflammatory response to mechanical ventilation and are involved in breakdown of the basement membrane and parenchymal modeling. OBJECTIVES: The aim of this study was to test the hypothesis that rhCC10, a lung anti-inflammatory mediator, would foster improved lung function, structural preservation, and a reduction in net MMP activity in a juvenile model of acute lung injury. METHODS: Twenty-four juvenile rabbits were saline-lavage-injured and treated with 100 or 25 mg/kg surfactant (Survanta, Ross Labs) with or without rhCC10 (Claragen, Inc.; n=6 per group). Animals were ventilated for 4 h, then euthanized for in vitro surfactant function analysis, lung histomorphometry, and analysis of MMP-2, MMP-7, and MMP-9 and TIMPs 1 and 2 in the lung. RESULTS: Apical lung expansion, reduced with the lower dose of surfactant, was partially restored with the addition of rhCC10. Alveolar septal wall thickness was reduced (p<0.05) with low-dose surfactant plus rhCC10 compared to high-dose surfactant alone. Increased within-group variance in MMP-2 and MMP-9 proteolytic activity was found with the low-dose surfactant and was abolished with rhCC10. MMP-7 was reduced (p<0.05) with rhCC10 administration, independent of surfactant dose. CONCLUSIONS: Intratracheal administration of the anti-inflammatory rhCC10 resulted in preserved lung structure and MMP/TIMP profile after 4 h of mechanical ventilation, in a surfactant dose-dependent manner.

Animals↗

PubMed2005

Dose response to rhCC10-augmented surfactant therapy in a lamb model of infant respiratory distress syndrome: physiological, inflammatory, and kinetic profiles.

While surfactant (SF) therapy alone improves respiratory distress syndrome (RDS)-associated gas exchange and lung stability, absence of anti-inflammatory proteins limits efficacy with respect to inflammation. Clara cell secretory protein (CC10), deficient in preterm infants, prevents SF degradation and has anti-inflammatory properties. In this study, intratracheal recombinant human (rh) CC10 (Claragen)-augmented SF (Survanta, Ross) therapy was examined in a premature lamb model of RDS with respect to inflammation and kinetic dose-response profiles. Preterm lambs (n = 24; gestational age: 126 +/- 3 days) were delivered via cesarean section, sedated, ventilated, and randomized into groups: 100 mg/kg SF, 100 mg/kg SF followed by 0.5 mg/kg rhCC10, 100 mg/kg SF followed by 1.5 mg/kg rhCC10, and 100 mg/kg SF followed by 5.0 mg/kg rhCC10. Arterial blood chemistry and lung mechanics were monitored; lungs were lavaged and snap-frozen after 4 h. TNF-alpha, IL-8 in plasma; TNF-alpha, IL-6, IL-8, myeloperoxidase in lung; and rhCC10 in plasma, urine, bronchoalveolar lavage, and lung were analyzed. Improvement in compliance, peak inspiratory pressure, and ventilatory efficiency index were greatest (P < 0.05) with SF + 5.0 mg/kg rhCC10. Plasma, urine, bronchoalveolar lavage, and lung [rhCC10] (where brackets denote concentration) increased (P < 0.01) with dose. Plasma [IL-8] was lower (P < 0.05) with rhCC10 than SF alone. Treatment with at least 1.5 mg/kg rhCC10 resulted in lower (P < 0.05) lung [TNF-alpha], [IL-8], and [myeloperoxidase]; SF + 1.5 mg/kg rhCC10 group had lower (P < 0.05) lung [IL-6], compared with all other groups. Compared with SF alone, SF augmented with at least 1.5 mg/kg rhCC10 decreased RDS-induced lung and systemic inflammation. Given that inflammation may lead to functional compromise, these data suggest that early intervention with rhCC10 may enhance SF therapy and warrant longer duration studies to determine its role to decrease long-term complications of ventilator management.

Animals↗

PubMed2005

Neonatal chest wall suspension splint: a novel and noninvasive method for support of lung volume.

Surfactant and musculoskeletal immaturity results in lower compliance of the lung relative to the chest wall, with clinical manifestations of low lung volume, marked chest wall retractions (CWR), and thoracoabdominal asynchrony. Inspiratory efforts are dissipated on distorting the chest wall inward rather than recruiting lung volumes. The current study tests the hypothesis that a novel neonatal chest wall suspension splint (SP), designed to provide stability to the compliant chest wall, would reduce inspiratory chest wall retractions and improve lung volumes. Nine preterm infants (29 +/- 1 SE weeks of gestation; 1.59 +/- 0.27 SE kg study weight) were studied at 16 +/- 5 SE days of life at baseline (BL) and following application of the front plate (FP) and the full SP (Hug n Snug Neonatal Chest Splint, Respironics, Inc.). Phase angle of thoracoabdominal motion, CWR, functional residual capacity (FRC), and pulmonary function were evaluated during spontaneous breathing. Compared to BL, there was a significant decrease in anterior CWR (2.21 +/- 0.91 SE vs. 0.25 +/- 0.09 SE mm; P < 0.05), an increase in FRC (16.6 +/- 2.8 SE vs. 27.8 +/- 5.5 SE ml/kg; P < 0.05) and tidal volume (4.8 +/- 1.5 SE vs. 7.3 +/- 1.4 SE ml/kg; P < 0.05), minimal effect on pulmonary compliance (1.98 +/- 0.50 SE vs. 1.72 +/- 0.30 SE ml/cmH2O/kg), and a trend for a decrease in phase angle (128.4 +/- 10.9 SE vs. 111.8 +/- 19.3 SE) with the application of the splint. FRC correlated inversely with severity of CWR across all conditions (P < 0.05, r = -0.68). Phase angle was directly correlated to anterior CWR (r = 0.72; P < 0.05) and correlated inversely with FRC (P < 0.005; r = -0.56). We speculate that by improving CW stability, the use of this splint may reduce the energetic requirements of breathing and, potentially, the need for more invasive ventilatory support in the neonate.

Female↗

PubMed2005

Heliox attenuates lung inflammation and structural alterations in acute lung injury.

Low-density gas mixtures, such as heliox, were shown to reduce the work of breathing and facilitate the distribution of inspired gas. Since supplemental ventilatory and oxygen requirements may lead to pulmonary inflammation and structural alterations, we hypothesized that by reducing these requirements, heliox breathing may attenuate the acute inflammatory and structural changes associated with acute lung injury. Spontaneously breathing neonatal pigs were anesthetized, instrumented, supported with continuous positive airway pressure (CPAP), injured with oleic acid, and randomized to nitrox (n = 6) or heliox (n = 5).F(I)O(2) was titrated for pulse oximetry (SpO(2)) 95 +/- 2% for 4 hr. Gas exchange and pulmonary mechanics were measured. Lungs were analyzed for myeloperoxidase (MPO), interleukin-8 (IL-8), and histomorphometery. Relationships between physiologic indices and cumulative lung structure and inflammatory indices were evaluated. With heliox, compliance was significantly greater, while tidal volume, frequency, minute ventilation, F(I)O(2), arterial carbon dioxide tension (PaCO(2)), MPO, and IL-8 were significantly lower compared to nitrox. The expansion index and number of exchange units were significantly greater with heliox, while the exchange unit area (EUA) was smaller. MPO was significantly and positively correlated with F(I)O(2) (r = 0.76) and EUA (r = 0.63), and negatively correlated with number of open exchange units/field (r = -0.73). Compared to breathing nitrox, these data indicate that heliox improved the distribution of inspired gas, thereby recruiting more gas exchange units, improving gas exchange efficiency, reducing ventilatory and oxygen requirements, and attenuating lung inflammation. These data suggest that heliox breathing may have the combined therapeutic benefits of attenuating lung inflammation by reducing mechanical and oxidative stress in the clinical management of acute lung injury.

Animals↗

PubMed2005

Pulmonary applications of perfluorochemical liquids: ventilation and beyond.

In this review of liquid ventilation, concepts and applications are presented that summarise the pulmonary applications of perfluorochemical liquids. Beginning with the question of whether this alternative form of respiratory support is needed and ending with lessons learned from clinical trials, the various methods of liquid assisted ventilation are compared and contrasted, evidence for mechanoprotective and cytoprotective attributes of intrapulmonary perfluorochemical liquid are presented and alternative intrapulmonary applications, including their use as vehicles for drugs, for thermal control and as imaging agents are presented.

Clinical Trials as Topic↗

PubMed2005

Differential impact of perfluorochemical physical properties on the physiologic, histologic, and inflammatory profile in acute lung injury.

OBJECTIVE: To evaluate the differential effects of physical properties of combinational perfluorochemical liquids (PFC) during partial liquid ventilation (PLV) on inflammatory indexes in the injured lung. DESIGN: : Interventional laboratory study. SETTING: Academic medical research laboratory. SUBJECTS: Seventeen saline lavage-injured juvenile rabbits. INTERVENTIONS: Rabbits were anesthetized, ventilated, saline lavage-injured, and randomized into groups: group 1 (conventional mechanical ventilation alone-no PFC), group 2 (PLV: lowest viscosity, highest vapor pressure), group 3 (PLV: mid-viscosity, mid-vapor pressure), group 4 (PLV: highest viscosity, lowest vapor pressure). MEASUREMENTS AND MAIN RESULTS: Arterial blood chemistry and pulmonary mechanics were monitored throughout the protocol. Following 4 hrs, lung tissue was harvested for interleukin-8, myeloperoxidase, and histologic analyses. Oxygenation (Pao2), ventilation (ventilation efficiency index), and respiratory compliance were not significantly different between groups before or following injury. Pao2 increased significantly following treatment in groups 3 and 4. Oxygenation index was significantly lower and respiratory compliance and ventilation efficiency index were significantly higher for group 4 following 4 hrs than all other groups. Total lung tissue interleukin-8 was significantly lower in groups 3 and 4 than groups 1 and 2, and lung myeloperoxidase was significantly lower in all PLV-treated groups than CMV alone. Histologic examination showed increased recruitment of the dependent lung in groups 3 and 4, with significantly greater lung expansion index, than groups 1 and 2. CONCLUSIONS: PLV, with a single dose of higher viscosity and lower vapor pressure PFC, resulted in significantly improved gas exchange and lung mechanics with significant reduction in lung inflammation compared with conventional mechanical ventilation alone and PLV with lower viscosity and higher vapor pressure liquid. Since PFC evaporative loss and redistribution are minimized by lower VP and higher viscosity, these data suggest that greater mechanoprotection and cytoprotection of the lung are conferred during PLV with PFC liquids that remain distributed throughout the entire lung for a longer duration.

Animals↗

PubMed2005

Tracheal gas insufflation as a lung-protective strategy: physiologic, histologic, and biochemical markers.

OBJECTIVE: Conventional mechanical ventilation in acute lung failure potentiates lung injury, which can be assessed by physiologic, histologic, and biochemical markers. Thus, new ventilation strategies are directed at reducing lung injury. Tracheal gas insufflation has been shown to reduce endotracheal tube prosthetic deadspace and peak inspiratory pressure during conventional mechanical ventilation. Our objective was to use physiologic, histologic, and biochemical markers to test the hypothesis that tracheal gas insufflation in acute lung injury is lung protective. DESIGN: Animal experiment. SETTING: University setting. SUBJECTS: Juvenile rabbits (n = 12; 1.95 +/- 0.1 SE kg). INTERVENTIONS: Rabbits were anesthetized, instrumented, paralyzed, and ventilated with Fio(2) = 1.0. Lung injury was induced with repeated saline lavage (10 mL/kg per lavage until Pao(2) </=150 mm Hg and compliance </=0.50 mL/cm H(2)O/kg for 30 mins). Animals were randomized to conventional mechanical ventilation with and without 0.5 lpm of continuous tracheal gas insufflation (Vygon endotracheal tube) for 4 hrs to maintain Paco(2) at 45-55 mm Hg by adjusting the peak inspiratory pressure; other conventional mechanical ventilation settings remained constant. MEASUREMENTS AND MAIN RESULTS: Gas exchange and pulmonary mechanics were measured every 30 mins; plasma and pulmonary tissue were taken for cytokine and histologic evaluation after 4 hrs. Peak inspiratory pressure, tidal volume, and physiologic deadspace were significantly less (p < .05) in the tracheal gas insufflation animals when compared with conventional mechanical ventilation animals. Pao(2), positive end-expiratory pressure, mean airway pressure, vital signs, Paco(2), and respiratory resistance and compliance were not statistically different between the two groups. There was a difference (p < .05) in interleukin-8 tissue (pg/mug protein; dependent = 52.4 +/- 7.6 vs. nondependent = 32.8 +/- 4.2) and plasma levels (pg/mL; preinjury = 7.2 +/- 2.3 vs. postinjury = 118 +/- 58). Histology showed a trend toward protection of alveolar structures for tracheal gas insufflation. CONCLUSIONS: Tracheal gas insufflation resulted in lower ventilatory requirements (peak inspiratory pressure, tidal volume, and deadspace) and a more favorable histologic trend than conventional mechanical ventilation. Tracheal gas insufflation offers potential as a lung-protective strategy for acute lung injury in the developing rabbit lung and may be a useful clinical adjunct to neonatal respiratory management.

Animals↗

PubMed2005

Recombinant human Clara cell secretory protein in acute lung injury of the rabbit: effect of route of administration.

OBJECTIVE: To test the hypothesis that intratracheal instillation of Clara cell secretory protein (CC 10) to the lung may afford greater protection than intravenous administration from ventilator-induced lung inflammation. DESIGN: Interventional laboratory study. SETTING: An academic medical research facility in northeastern United States. SUBJECTS: Sedated, lavage-injured juvenile rabbits. INTERVENTIONS: A total of 18 juvenile rabbits were anesthetized, ventilated, injured with saline lavage (Pao2 of <100 mm Hg; respiratory compliance of <0.50 mL.cm H2O.kg and <50% baseline), and randomized to receive intratracheally administered surfactant plus no recombinant human CC 10 (rhCC 10, control), intravenous rhCC 10, or intratracheal rhCC 10. MEASUREMENT AND MAIN RESULTS: Arterial blood chemistry and pulmonary mechanics were monitored; plasma and urine were collected serially. After 4 hrs of ventilation, lungs were lavaged and harvested. Surfactant function was analyzed from bronchoalveolar lavage samples (surfactometry); rhCC 10, interleukin-8, and lung myeloperoxidase concentrations were measured. Pao2, oxygenation index, ventilatory efficiency index, and respiratory compliance were not different across time or group beyond injury. Surfactometry data identified no differences as a function of group or time. Plasma, bronchoalveolar lavage, and lung interleukin-8 concentrations, lung myeloperoxidase concentrations, and inflammatory cell counts in the alveolar and interstitial spaces of intravenous and intratracheal groups were lower than in the control group (p < .05) but not statistically different from each other. Concentrations of rhCC 10 in lung, bronchoalveolar lavage, and plasma were greater in the intratracheal group than in the intravenous group (p<.05). Urine rhCC 10 concentrations were greater for the intravenous group than for the intratracheal group (p<.05) at 1, 3, and 4 hrs after treatment. No group differences in histomorphometry were noted. CONCLUSIONS: Both intravenous and intratracheal rhCC 10 delivery, after surfactant therapy, effectively decrease lung inflammation vs. surfactant alone. While supporting the physiologic profile, intratracheal instillation results in greater, maintained lung and plasma rhCC 10 pools compared with intravenous administration. As such, intratracheal instillation of rhCC 10 may afford more prolonged protection against lung inflammation than intravenous administration.

Animals↗

PubMed2004

Liquid ventilation: an adjunct for respiratory management.

Although significant advances in respiratory care have reduced mortality of patients with respiratory failure, morbidity persists, often resulting from iatrogenic mechanisms. Mechanical ventilation with gas has been shown to initiate as well as exacerbate underlying lung injury, resulting in progressive structural damage and release of inflammatory mediators within the lung. Alternative means to support pulmonary gas exchange while preserving lung structure and function are therefore required. Perfluorochemical (PFC) liquids are currently used clinically in a number of ways, such as intravascular PFC emulsions for volume expansion/oxygen carrying/angiography and intracavitary neat PFC liquid for image contrast enhancement or vitreous fluid replacement. As a novel approach to replace gas as the respiratory medium, liquid assisted ventilation (LAV) with PFC liquids has been investigated as an alternative respiratory modality for over 30 years. Currently, there are several theoretical and practical applications of LAV in the immature or mature lung at risk for acute respiratory distress and injury associated with mechanical ventilation.

Adult↗

PubMed2004

Airway structure, function and development in health and disease.

Until they are fully mature, the airways are highly susceptible to damage. Factors that may contribute to vulnerability of immature airways and the occurrence of bronchopulmonary dysplasia (BPD) in preterm neonates include decreased contractility of smooth muscles of the airway, which leads to generation of lower forces, and immaturity of airway cartilage, leading to increased compressibility of developing airways. Mechanical ventilation has little effect on adult airways, but affects the dimensions and mechanical properties of preterm and newborn airways. Techniques for clinical evaluation of airway function include: (i). measurements of airway function during tidal breathing (airway resistance and reactivity are significantly elevated in infants with BPD); (ii). forced expiratory flow measurements [small-airway obstruction in infants with BPD is indicated by markedly reduced maximal volume measurements (Vmax)]; (iii). radiography procedures (plain radiographs, fluoroscopy, computed tomography and virtual bronchoscopy); and (iv). endoscopy procedures (rigid or flexible bronchoscopy, with or without measurement of oesophageal pressure). Imaging has demonstrated an excessively decreased airway cross-sectional area during exhalation in infants with BPD and acquired tracheomegaly in very preterm infants who had received mechanical ventilatory support. To further advance our understanding of how the airways develop, and to design less damaging protocols for mechanical ventilation in preterm neonates, basic laboratory studies of airway ultrastructure need to be performed and the results correlated with clinical pulmonary function studies.

Animals↗

PubMed2003

Continuous tracheal gas insufflation during partial liquid ventilation in juvenile rabbits with acute lung injury.

To examine the hypothesis that combined treatment with tracheal gas insufflation (TGI) and partial liquid ventilation (PLV) may improve pulmonary outcome relative to either treatment alone in acute lung injury (ALI), saline lavage lung injury was induced in 24 anesthetized, ventilated juvenile rabbits that were then randomly assigned to receive (n = 6/group) 1) conventional mechanical ventilation (CMV) alone, 2) continuous TGI at 0.5 l/min, 3) PLV with perfluorochemical liquid, and 4) combined TGI and PLV (TGI + PLV), and subsequently ventilated with minimized pressures and tidal volume (Vt) to keep arterial Po(2) (Pa(O(2))) >100 Torr and arterial Pco(2) (Pa(CO(2))) at 45-60 Torr for 4 h. Gas exchange, lung mechanics, myeloperoxidase, IL-8, and histomorphometry [including expansion index (EI)] were assessed. The CMV group showed no improvement in lung mechanics and gas exchange; all treated groups had significant increases in compliance, Pa(O(2)), ventilation efficacy index (VEI), and EI, and decreases in PaCO(2), oxygenation index, physiological dead space-to-Vt ratio (Vd/Vt), myeloperoxidase, and IL-8, relative to the CMV group. TGI resulted in lower peak inspiratory pressure, Vt, Vd/Vt, and greater VEI vs. PLV group; PLV resulted in greater compliance, Pa(O(2)), and EI vs. TGI. TGI + PLV resulted in decreased peak inspiratory pressure, Vt, Vd/Vt, and increased VEI compared with TGI, improved compliance and EI compared with PLV, and a further increase in Pa(O(2)) and oxygenation index and a decrease in PaCO(2) vs. either treatment alone. These results indicate that combined treatment of TGI and PLV results in improved pulmonary outcome than either treatment alone in this animal model of ALI.

Analysis of Variance↗

PubMed2003

Long-term tidal liquid ventilation in premature lambs: physiologic, biochemical and histological correlates.

Chronic lung disease in infants continues to be problematic. Tidal liquid ventilation (TLV) improves lung mechanics and provides effective gas exchange. We hypothesized that premature lambs could be supported safely with TLV and evaluated 9 preterm lambs (132 days gestation) on TLV up to 72 h. Results (mean +/- SEM): pH 7.36 +/- 0.003, PaCO2 44 +/- 0.34 mm Hg, PaO2 170 +/- 4.8 mm Hg, compliance=1.65 +/- 0.24 ml/cm H2O/kg, mean arterial blood pressure=53 +/- 0.08 mm Hg, heart rate=189 +/- 1.5 bpm. Blood perflubron levels were 6.0 +/- 0.24 microg/ml over 24 h. Tissue perflubron levels increased from 81 +/- 7.0 microg/g at 24 h to 108 +/- 15 microg/g at 72 h (p<0.05). There was a difference in perflubron concentrations as a function of tissue (p<0.001) that correlated to lipid levels (r2=0.93, p<0.01). These data demonstrate that TLV is both safe and effective up to 72 h in premature lambs.

Animals↗

PubMed2003

Perfluorochemical (PFC) combinations for acute lung injury: an in vitro and in vivo study in juvenile rabbits.

Perfluorochemical (PFC) fluids of different physical properties were titrated and tested in vitro for physical properties that are appropriate for respiratory application. Two PFC liquids were studied: perfluoromethylcyclohexane (PP2), a liquid with high vapor pressure and low viscosity, and perfluoromethyldecalin (PP9), a fluid with low vapor pressure and high viscosity. Eighteen rabbits (2.05 +/- 0.07 kg; mean +/- SEM) were lung-lavaged and randomized: group I, control group; group II, partial liquid ventilation with 75% PP2 and 25% PP9; group III, partial liquid ventilation with 50% PP2 and 50% PP9; and group IV, partial liquid ventilation with 25% PP2 and 75% PP9. Ventilator volumes were kept constant during the 4-h experiment. Cardiopulmonary measurements were performed every 30 min. The lung histology was examined. The in vitro study showed PFC [viscosity/vapor pressure (in cS and mm Hg, respectively)] as follows: 100% PP2 (0.88/141); 100% PP9 (3.32/2.9); 75% PP2 and 25% PP9 (1.26/107); 50% PP2 and 50% PP9 (1.63/13.7); and 25% PP2 and 75% PP9 (2.21/4.4). The in vivo experiments found that combinations of moderate vapor pressure (groups 3 and 4) demonstrated good gas exchange, compliance, and histologic findings. Thus, combinations of PFC liquids can be formulated to modulate the physiologic outcome in acutely injured lungs, and may prove useful for alternative PFC liquid applications.

Animals↗

PubMed2002

Physicochemical properties of perfluorochemical liquids influence ventilatory requirements, pulmonary mechanics, and microvascular permeability during partial liquid ventilation following intestinal ischemia/reperfusion injury.

OBJECTIVE: To test the hypothesis that the physicochemical properties of perfluorochemical liquid used in partial liquid ventilation can influence ventilatory requirements, pulmonary mechanics, microvascular permeability, and vasoactive mediator release in the abnormal lung. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory in a university setting. SUBJECTS Male Sprague-Dawley rats: sham and intestinal ischemia/reperfusion injury. INTERVENTIONS: Treatment with perfluorochemical partial liquid ventilation (PLV: PP-5 or H-130) or conventional mechanical ventilation (CMV) over 60 mins of superior mesenteric artery occlusion and 60 mins of reperfusion. MEASUREMENTS AND MAIN RESULTS: Gas exchange, ventilatory requirements, and pulmonary mechanics were measured in vivo. Subsequently, pulmonary vascular resistance, microvascular permeability, and thromboxane were measured by using the isolated perfused lung preparation. PLV with PP-5 required significantly (p <.05) higher positive end-expiratory pressure resulting in increased mean airway pressures and pulmonary vascular resistance in both sham and intestinal ischemia/reperfusion injured animals compared with those treated with CMV or PLV H-130. PLV PP-5 also resulted in significantly (p <.05) lower respiratory compliance and greater microvascular permeability compared with sham animals. Following intestinal ischemia/reperfusion injury, PLV H-130 treated animals had significantly higher (p <.05) respiratory compliance than those treated with PLV PP-5 and a significantly lower (p <.05) intestinal ischemia/reperfusion-mediated increase in microvascular permeability than those treated with CMV or PLV PP-5. Thromboxane levels were significantly higher (p <.01) in injured animals treated with CMV or PLV PP-5 compared with comparably treated shams, were significantly lower (p <.01) in both PLV groups than CMV, and were further attenuated (p <.01) by PLV H-130 compared with PLV PP-5 animals. CONCLUSION: We conclude that PLV with perfluorochemical liquids attenuates pulmonary sequelae resulting from remote organ injury and that the extent of lung protection depends on the physicochemical properties of the perfluorochemical liquids.

Animals↗