Effects of perfluorochemical distribution and elimination dynamics on cardiopulmonary function.

Based on a physicochemical property profile, we tested the hypothesis that different perfluorochemical (PFC) liquids may have distinct effects on intrapulmonary PFC distribution, lung function, and PFC elimination kinetics during partial liquid ventilation (PLV). Young rabbits were studied in five groups [healthy, PLV with perflubron (PFB) or with perfluorodecalin (DEC); saline lavage injury and conventional mechanical ventilation (CMV); saline lavage injury PLV with PFB or with DEC]. Arterial blood chemistry, respiratory compliance (Cr), quantitative computed tomography of PFC distribution, and PFC loss rate were assessed for 4 h. Initial distribution of PFB was more homogenous than that of DEC; over time, PFB redistributed to dependent regions whereas DEC distribution was relatively constant. PFC loss rate decreased over time in all groups, was higher with DEC than PFB, and was lower with injury. In healthy animals, arterial PO(2) (Pa(O(2))) and Cr decreased with either PFC; the decrease was greater and sustained with DEC. Lavaged animals treated with either PFC demonstrated increased Pa(O(2)), which was sustained with PFB but deteriorated with DEC. Lavaged animals treated with PFB demonstrated increased Cr, higher Pa(O(2)), and lower arterial PCO(2) than with CMV or PLV with DEC. The results indicate that 1) initial distribution and subsequent intrapulmonary redistribution of PFC are related to PFC properties; 2) PFC distribution influences PFC elimination, gas exchange, and Cr; and 3) PFC elimination, gas exchange, and Cr are influenced by PFC properties and lung condition.     

Enhanced clearance of surfactant protein D during LPS-induced acute inflammation in rat lung

Pulmonary surfactant participates in the regulation of alveolar compliance and lung host defense. Surfactant homeostasis is regulated through a combination of synthesis, secretion, clearance, recycling, and degradation of surfactant components. The extracellular pool size of surfactant protein (SP) D fluctuates significantly during acute inflammation. We hypothesized that changes in SP-D levels are due, in part, to altered clearance of SP-D. Clearance pathways in rats were assessed with fluorescently labeled SP-D that was instilled into control lungs or lungs that had been treated with lipopolysaccharide (LPS) 16 h earlier. SP-D clearance from lavage into lung tissue was time dependent from 5 min to 1 h and 1.7-fold greater in LPS-treated lungs than in control lungs. Analysis of cells isolated by enzymatic digestion of lung tissue revealed differences in the SP-D-positive cell population between groups. LPS-treated lungs had 28.1-fold more SP-D-positive tissue-associated neutrophils and 193.6-fold greater SP-D association with those neutrophils compared with control lungs. These data suggest that clearance of SP-D into lung tissue is increased during inflammation and that tissue-associated neutrophils significantly contribute to this process.     

Protective effect of lung inflation in reperfusion-induced lung microvascular injury

We used the isolated-perfused rat lung model to study the influence of pulmonary ventilation and surfactant instillation on the development of postreperfusion lung microvascular injury. We hypothesized that the state of lung inflation during ischemia contributes to the development of the injury during reperfusion. Pulmonary microvascular injury was assessed by continuously monitoring the wet lung weight and measuring the vessel wall (125)I-labeled albumin ((125)I-albumin) permeability-surface area product (PS). Sprague-Dawley rats (n = 24) were divided into one control group and five experimental groups (n = 4 rats per group). Control lungs were continuously ventilated with 20% O(2) and perfused for 120 min. All lung preparations were ventilated with 20% O(2) before the ischemia period and during the reperfusion period. The various groups differed only in the ventilatory gas mixtures used during the flow cessation: group I, ventilated with 20% O(2); group II, ventilated with 100% N(2); group III, lungs remained collapsed and unventilated; group IV, same as group III but pretreated with surfactant (4 ml/kg) instilled into the airway; and group V, same as group III but saline (4 ml/kg) was instilled into the airway. Control lungs remained isogravimetric with baseline (125)I-albumin PS value of 4.9 +/- 0.3 x 10(-3) ml x min(-1) x g wet lung wt(-1). Lung wet weight in group III increased by 1.45 +/- 0.35 g and albumin PS increased to 17.7 +/- 2.3 x 10(-3), indicating development of vascular injury during the reperfusion period. Lung wet weight and albumin PS did not increase in groups I and II, indicating that ventilation by either 20% O(2) or 100% N(2) prevented vascular injury. Pretreatment of collapsed lungs with surfactant before cessation of flow also prevented the vascular injury, whereas pretreatment with saline vehicle had no effect. These results indicate that the state of lung inflation during ischemia (irrespective of gas mixture used) and supplementation of surfactant prevent reperfusion-induced lung microvascular injury.     

Regional VA, Q, and VA/Q during PLV: effects of nitroprusside and inhaled nitric oxide.

Partial liquid ventilation (PLV) with high-specific-weight perfluorocarbon liquids has been shown to improve oxygenation in acute lung injury, possibly by redistributing perfusion from dependent, injured regions to nondependent, less injured regions of the lung. Our hypothesis was that during PLV in normal lungs, a shift in perfusion away from dependent lung zones might, in part, be due to vasoconstriction that could be reversed by infusing sodium nitroprusside (NTP). In addition, delivering inhaled NO during PLV should improve gas exchange by further redistributing blood flow to well-ventilated lung regions. To examine this, we used a single transverse-slice positron emission tomography camera to image regional ventilation and perfusion at the level of the heart apex in six supine mechanically ventilated sheep during five conditions: control, PLV, PLV + NTP, and PLV + NO at 10 and 80 ppm. We found that PLV shifted perfusion from dependent to middle regions, and the dependent region demonstrated marked hypoventilation. The vertical distribution of perfusion changed little when high-dose intravenous NTP was added during PLV, and inhaled NO tended to shift perfusion toward better ventilated middle regions. We conclude that PLV shifts perfusion to the middle regions of the lung because of the high specific weight of perflubron rather than vasoconstriction.     

Early surfactant administration protects against lung dysfunction in a mouse model of ARDS

Sepsis can predispose the lung to insults such as mechanical ventilation (MV). It was hypothesized that treating the lung with exogenous surfactant early in the development of sepsis will reduce the lung dysfunction associated with MV 18 h later. Mice underwent sham or cecal ligation and perforation (CLP) surgery. Immediately after surgery, mice were either untreated or given 100 mg/kg of bovine lipid extract surfactant intratracheally. Eighteen hours later, the lungs were removed and analyzed either immediately or following ventilation ex vivo for 2 h by an "injurious" mode of ventilation (20 ml/kg, 0 cm positive end-expiratory pressure). In nonventilated lungs, exogenous surfactant had no impact on compliance or IL-6 concentrations in the lungs. In the ventilated groups, the administered surfactant had a significant protective effect on the lung dysfunction induced by MV, but only in the CLP lungs. We conclude that administration of exogenous surfactant at the time of a systemic insult can protect the lung from the damaging effects of MV 18 h later.     

Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency

Wolfson, Marla R., Nancy E. Kechner, Robert F. Roache,Jean-Pierre DeChadarevian, Helena E. Friss, S. David Rubenstein, andThomas H. Shaffer. Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency. J. Appl. Physiol. 84(2): 624-640, 1998.To test the hypotheses that perfluorochemical (PFC) liquidrescue after natural surfactant (SF) treatment would improve pulmonaryfunction and histology and that this profile would be influenced by PFCdose or ventilator strategy, anesthetized preterm lambs(n = 31) with respiratory distresswere studied using nonpreoxygenated perflubron. All animals received SFat 1 h and were randomized at 2 h as follows and studied to 4 h postnatal age: 1) conventionalmechanical gas ventilation (n = 8),2) 30 ml/kg perflubron with gasventilation [partial liquid ventilation (PLV)] at 60 breaths/min (n = 8),3) 10 ml/kg perflubron with PLV at60 breaths/min (n = 7), and4) 10 ml/kg perflubron with PLV at30 breaths/min (n = 8). All animalstolerated instillation without additional cardiopulmonary instability.All perflubron-rescued groups demonstrated sustained improvement in gasexchange, respiratory compliance, and reduction in pressure requirements relative to animals receiving SF alone. Improvement wasdirectly related to perflubron dose and breathing frequency; peakinspiratory pressure required to achieve physiological gas exchange waslower in the higher-dose and -frequency groups, and mean airwaypressure was lower in the lower-frequency group. Lung expansion wasgreater and evidence of barotrauma was less in the higher-dose and-frequency group; regional differences in expansion were not differentas a function of dose but were greater in the lower-frequency group.Regional differences in lung perflubron content were reduced in thehigher-dose and -frequency groups and greatest in the lower-dose and-frequency group. The results suggest that, whereas PLV of theSF-treated lung improves gas exchange and lung mechanics, theprotective benefits of perflubron in the lung may depend on dose andventilator strategy to optimize PFC distribution and minimize exposureof the alveolar-capillary membrane to a gas-liquid interface.

     

Effect of artificial surfactant on pulmonary function in preterm and full-term lambs

We hypothesized that agents very different from surfactant may still support lung function. To test this hypothesis, we instilled FC-100, a fluorocarbon, and Tween 20, a detergent, which have higher minimum surface tensions and less hysteresis than surfactant, into 15 full-term and 14 preterm lambs. FC-100 and Tween 20 were as efficient as natural surfactant in improving gas exchange and compliance in preterm lambs with respiratory failure. Dynamic compliance correlated with the equilibrium surface tension of the alveolar wash in both full-term (P less than 0.02) and preterm (P less than 0.008) lambs. Functional residual capacity in full-term and preterm lambs was lower after treatment with the two test agents than with surfactant, findings consistent with qualitative histology. Oxygenation in full-term lambs correlated with mean lung volumes (P less than 0.003), suggesting that the hysteresis and/or low minimum surface tension of surfactant may improve mean lung volume, and hence oxygenation, by maintaining functional residual capacity. The effects of the test agents suggest that agents with biophysical properties different from surfactant may still aid lung expansion.     

A perfluorochemical loss/restoration (L/R) system for tidal liquid ventilation

Tidal liquid ventilation is the transport of dissolved respiratory gases via volume exchange of perfluorochemical (PFC) liquid to and from the PFC-filled lung. All gas-liquid surface tension is eliminated, increasing compliance and providing lung protection due to lower inflation pressures. Tidal liquid ventilation is achieved by cycling fluid from a reservoir to and from the lung by a ventilator. Current approaches are microprocessor-based with feedback control. During inspiration, warmed oxygenated PFC liquid is pumped from a fluid reservoir/gas exchanger into the lung. PFC fluid is conserved by condensing (60-80% efficiency) vapor in the expired gas. A feedback-control system was developed to automatically replace PFC lost due to condenser inefficiency. This loss/restoration (L/R) system consists of a PFC-vapor thermal detector (+/- 2.5%), pneumatics, amplifiers, a gas flow detector (+/- 1%), a PFC pump (+/- 5%), and a controller. Gravimetric studies of perflubron loss from a flask due to evaporation were compared with experimental L/R results and found to be within +/- 1.4%. In addition, when L/R studies were conducted with a previously reported liquid ventilation system over a four-hour period, the L/R system maintained system perflubron volume to within +/- 1% of prime volume and 11.5% of replacement volume, and the difference between experimental PFC loss and that of the L/R system was 1.8 mL/hr. These studies suggest that the PFC L/R system may have significant economic (appropriate dosing for PFC loss) as well as physiologic (maintenance of PFC inventory in the lungs and liquid ventilator) impact on liquid ventilation procedures.     

A supervisor for volume-controlled tidal liquid ventilator using independent piston pumps

Liquid ventilation using perfluorochemicals (PFC) offers clear theoretical advantages over gas ventilation, such as decreased lung damage, recruitment of collapsed lung regions and lavage of inflammatory debris. This paper presents the control of a total liquid ventilator (TLV) dedicated to ventilate patients with completely filled lungs with a tidal volume of perfluorochemical liquid. The two independent piston pumps are volume controlled and pressure limited. Measurable pumping errors are corrected by a programmed supervisor module, which modifies the inserted or withdrawn volume. Pump independence also allows easy FRC modifications during ventilation. The prototype was tested on eight healthy term newborn lambs (<5 days old).     

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.     

Inhibition of breathing after surfactant depletion is achieved at a higher arterial PCO2 during ventilation with liquid than with gas

Background

Inhibition of phrenic nerve activity (PNA) can be achieved when alveolar ventilation is adequate and when stretching of lung tissue stimulates mechanoreceptors to inhibit inspiratory activity. During mechanical ventilation under different lung conditions, inhibition of PNA can provide a physiological setting at which ventilatory parameters can be compared and related to arterial blood gases and pH.

Objective

To study lung mechanics and gas exchange at inhibition of PNA during controlled gas ventilation (GV) and during partial liquid ventilation (PLV) before and after lung lavage.

Methods

Nine anaesthetised, mechanically ventilated young cats (age 3.8 ± 0.5 months, weight 2.3 ± 0.1 kg) (mean ± SD) were studied with stepwise increases in peak inspiratory pressure (PIP) until total inhibition of PNA was attained before lavage (with GV) and after lavage (GV and PLV). Tidal volume (V_t), PIP, oesophageal pressure and arterial blood gases were measured at inhibition of PNA. One way repeated measures analysis of variance and Student Newman Keuls-tests were used for statistical analysis.

Results

During GV, inhibition of PNA occurred at lower PIP, transpulmonary pressure (Ptp) and Vt before than after lung lavage. After lavage, inhibition of inspiratory activity was achieved at the same PIP, Ptp and Vt during GV and PLV, but occurred at a higher PaCO₂ during PLV. After lavage compliance at inhibition was almost the same during GV and PLV and resistance was lower during GV than during PLV.

Conclusion

Inhibition of inspiratory activity occurs at a higher PaCO₂ during PLV than during GV in cats with surfactant-depleted lungs. This could indicate that PLV induces better recruitment of mechanoreceptors than GV.     

Rapidly adapting receptor activity in dogs is inversely related to lung compliance

We examined the response of pulmonary rapidly adapting receptors (RAR's) to changes in dynamic lung compliance (Cdyn) in the physiological range. RAR impulse activity was recorded from the cervical vagus nerves in anesthetized open-chest dogs whose lungs were ventilated at constant rate and tidal volume (VT), with a positive end-expiratory pressure (PEEP) of 3-4 cmH2O. After hyperinflation to produce maximal Cdyn, RAR's were silent or fired sparsely and irregularly. Reducing Cdyn in steps by briefly removing PEEP increased firing proportionately, and RAR's began to discharge vigorously in inflation. Activity was restored to control by hyperinflating the lungs. Activity also increased when we increased inflation rate, and hence the rate of change of airway pressure (dP/dt), by reducing inflation time, keeping VT and cycle length constant. RAR's were stimulated more when dP/dt was increased by reducing compliance than when dP/dt was increased by increasing inflation rate. We conclude that RAR's are sensitive to changes in Cdyn and speculate that excitatory input from RAR's may help to maintain VT as the lungs become stiffer.     

Massive postmortem bronchoconstriction in guinea pig lungs

A special phenomenon (difficult to inflate and deflate) occurring in the postmortem guinea pig lungs was studied in 40 animals. Thirty minutes after excision of the lungs or exsanguination, less than 50% of the lungs could be inflated even at high inflation pressure (34 cmH2O), and most gas was trapped during deflation. The amount of trapped gas volume at 30 min was related to the degree of lung inflation maintained during the 5- to 30-min period after exsanguination. Since stiffness of the lung tissue was unlikely to explain the phenomenon, we speculated airway obstruction as the major factor. No foam or bubbles were found in larger airways and we thus hypothesized that the obstruction was due to bronchoconstriction. This was confirmed histologically in that the lumina of both bronchi and bronchioles were constricted. The latent period to the onset of this constriction was short (approximately 5 min). It was not associated with O2 availability but was delayed an additional 15 min by a thromboxane inhibitor (dazoxiben). Neither maintaining lung temperature at 37 degrees C nor vagotomy and/or cervical transection prevented the constriction. Without exsanguination, onset of bronchoconstriction was delayed by about 1 h. We conclude that postmortem bronchoconstriction may be caused by release of an endogenous constrictor agent.     

A mathematical model of alveolar gas exchange in partial liquid ventilation

In partial liquid ventilation (PLV), perfluorocarbon (PFC) acts as a diffusion barrier to gas transport in the alveolar space since the diffusivities of oxygen and carbon dioxide in this medium are four orders of magnitude lower than in air. Therefore convection in the PFC layer resulting from the oscillatory motions of the alveolar sac during ventilation can significantly affect gas transport. For example, a typical value of the Péclet number in air ventilation is Pe approximately 0.01, whereas in PLV it is Pe approximately 20. To study the importance of convection, a single terminal alveolar sac is modeled as an oscillating spherical shell with gas, PFC, tissue and capillary blood compartments. Differential equations describing mass conservation within each compartment are derived and solved to obtain time periodic partial pressures. Significant partial pressure gradients in the PFC layer and partial pressure differences between the capillary and gas compartments (P(C)-Pg) are found to exist. Because Pe> 1, temporal phase differences are found to exist between P(C)-Pg and the ventilatory cycle that cannot be adequately described by existing non-convective models of gas exchange in PLV The mass transfer rate is nearly constant throughout the breath when Pe>1, but when Pe<1 nearly 100% of the transport occurs during inspiration. A range of respiratory rates (RR), including those relevant to high frequency oscillation (HFO) +PLV, tidal volumes (V(T)) and perfusion rates are studied to determine the effect of heterogeneous distributions of ventilation and perfusion on gas exchange. The largest changes in P(C)O2 and P(C)CO2 occur at normal and low perfusion rates respectively as RR and V(T) are varied. At a given ventilation rate, a low RR-high V(T) combination results in higher P(C)O2, lower P(C)CO2 and lower (P(C)-Pg) than a high RR-low V(T) one.     

Initial responses to ventilation of premature lambs exposed to intra-amniotic endotoxin 4 days before delivery

Preterm delivery is frequently preceded by chorioamnionitis, resulting in exposure of the fetal lung to inflammation. We hypothesized that ventilation of the antenatally inflamed lung would result in amplification of the lung injury. Therefore, we induced fetal lung inflammation with intra-amniotic endotoxin (10 mg of Escherichia coli 055:B5) 4 days before premature delivery at 130 days of gestation. Lung function and lung inflammation after surfactant treatment and 4 h of mechanical ventilation were evaluated. Inflammatory cell numbers in amniotic fluid were increased >10-fold by antenatal endotoxin exposure. Antenatal endotoxin exposure had minimal effects on blood pressure, heart rate, lung compliance, and blood gas values. The endotoxin-exposed lungs required higher ventilation pressures. Ventilation did not increase the number of inflammatory cells or the protein in bronchoalveolar lavage fluid of the endotoxin-exposed animals above that measured in endotoxin-exposed fetuses that were not ventilated. IL-1beta, IL-6, and IL-8 mRNA in cells from bronchoalveolar lavage fluid were increased by antenatal endotoxin exposure but not changed by ventilation. IL-1beta and IL-8 protein was increased in lung tissue by 4 h of ventilation. Very little inflammation was induced by ventilation in this premature lamb model of surfactant treatment and gentle ventilation. After lung inflammation was induced by intra-amniotic endotoxin injection, ventilation did not increase lung injury.     

Compliances of the liquid-filled lungs and chest wall during development in fetal sheep.

Our aim was to measure the compliance of the liquid-filled lungs (CL), and the compliance of the chest wall (CW) in fetal sheep in utero. CL and CW were measured in 6 fetuses. The compliance of the lungs and chest wall combined (respiratory system, Crs) was measured in 9 fetuses. Pressure differences across the lungs (PL), chest wall (PW) and respiratory system (Prs) were measured while the lungs were deflated and inflated with liquid from their resting lung liquid volume (V1). V1 was measured using an indicator dilution technique. Specific compliance values were obtained by normalizing the values of CL, CW and Crs with respect to values of V1. From values obtained during stepwise inflation from V1, specific compliances (ml/cm H2O/ml of lung liquid) were: lungs, 0.22 +/- 0.02; chest wall, 0.41 +/- 0.07; respiratory system, 0.13 +/- 0.01. Specific compliances of the lungs, chest wall and respiratory system did not change significantly with advancing gestational age from 120 to 143 days. Our baseline data will be valuable in assessing the in utero progress of the structural development of the lungs following manipulations known to cause altered lung growth.     

Delayed partial liquid ventilation shows no efficacy in the treatment of smoke inhalation injury in swine.

In an earlier neonatal porcine model of smoke inhalation injury (SII), immediate postinjury application of partial liquid ventilation (PLV) had dramatic beneficial effects on lung compliance, oxygenation, and survival over a 24-h period. To explore the efficacy of PLV following SII, we treated animals at 2 and 6 h after SII and followed them for 72 h. Pigs weighing 8-12 kg were sedated and pharmacologically paralyzed, given a SII, and placed on volume-cycled, pressure-limited ventilation. Animals were randomized to three groups: group I (+SII, no PLV, n = 8), group II (+SII, PLV at 2 h, n = 6), and group III (+SII, PLV at 6 h, n = 7). Ventilatory parameters and arterial blood gasses were obtained at scheduled intervals. The PLV animals (groups II and III) followed a worse course than group I (no PLV); PLV groups had higher peak and mean airway pressures, oxygenation index, and rate-pressure product (a barotrauma index) and lower lung compliance and arterial partial pressure of oxygen-to-inspired oxygen fraction ratio (all P < 0.05). PLV conferred no survival advantage. The reported beneficial effects of PLV with other models of acute lung injury do not appear to extend to the treatment of SII when PLV is instituted in a delayed manner. This study was not able to validate the previously reported beneficial effects of PLV in SII and actually found deleterious effects, perhaps reflecting the predominance of airway over alveolar disease in SII.     

Lung volume and interdependence in the pig.

The effect of lung volume on the mechanical interdependence between an obstructed sublobar region of lung and its surrounding tissues was investigated in intact and isolated pig lungs. Interdependence is arbitrarily defined as the effectiveness with which the linkage between the region and surrounding tissue mediates a tendency for inflation to become even whenever it is uneven. We found that when the volume of the surrounding lung (Vl) was high relative to the volume of the obstructed region (Vr), or when they were relatively equal at higher inflation states, interdependence decreased. When Vr was high relative changes in regional shape observed during even and uneven inflation states, we suggest that regional distortion and its effects on regional elastic recoil are important determinants of pulmonary interdependence.     

Ionotropic GABA receptor expression in the lung during development

Cl(-) transport is essential for lung development. Because gamma-aminobutyric acid (GABA) receptors allow the flow of negatively-charged Cl(-) ions across the cell membrane, we hypothesized that the expression of ionotropic GABA receptors are regulated in the lungs during development. We identified 17 GABA receptor subunits in the lungs by real-time PCR. These subunits were categorized into four groups: Group 1 had high mRNA expression during fetal stages and low in adults; Group 2 had steady expression to adult stages with a slight up-regulation at birth; Group 3 showed an increasing expression from fetal to adult lungs; and Group 4 displayed irregular mRNA fluctuations. The protein levels of selected subunits were also determined by Western blots and some subunits had protein levels that corresponded to mRNA levels. Further studied subunits were primarily localized in epithelial cells in the developing lung with differential mRNA expression between isolated cells and whole lung tissues. Our results add to the knowledge of GABA receptor expression in the lung during development.