Mean Transpulmonary Pressure Research Articles

Invasive haemodynamics predict outcomes in paediatric pulmonary artery hypertension.

Invasive haemodynamics are often performed for initiating and guiding pulmonary artery hypertension therapy. Little is known about the predictive value of invasive haemodynamic indices for long-term outcomes in children with pulmonary artery hypertension. We aimed to evaluate invasive haemodynamic data to help predict outcomes in paediatric pulmonary artery hypertension. Patients with pulmonary artery hypertension who underwent cardiac catheterisation (2006-2019) at a single centre were included. Invasive haemodynamic data from the first cardiac catheterisation and clinical outcomes were reviewed. The combined adverse outcome was defined as pericardial effusion (due to right ventricle failure), creation of a shunt for pulmonary artery hypertension (atrial septal defect or reverse Pott's shunt), lung transplant, or death. Among 46 patients with a median [interquartile range (IQR)] age of 13.2 [4.1-44.7] months, 76% had CHD. Median mean pulmonary artery pressure was 37 [28-52] mmHg and indexed pulmonary vascular resistance was 6.2 [3.6-10] Woods units × m2. Median pulmonary artery pulsatility index was 4.0 [3.0-4.7] and right ventricular stroke work index was 915 [715-1734] mmHg mL/m2. After a median follow-up of 2.4 years, nine patients had a combined adverse outcome (two had a pericardial effusion, one underwent atrial level shunt, one underwent reverse Pott's shunt, and six died). Patients with an adverse outcome had higher systolic and mean pulmonary artery pressures, higher diastolic and transpulmonary pressure gradients, higher indexed pulmonary vascular resistance, higher pulmonary artery elastance, and higher right ventricular stroke work index (p < 0.05 each). Invasive haemodynamics (especially mean pulmonary artery pressure and diastolic pressure gradient) obtained at first cardiac catheterisation in children with pulmonary artery hypertension predicts outcomes.

Effect and mechanical mechanism of spontaneous breathing on oxygenation and lung injury in mild or moderate animal ARDS

ObjectiveThe present study aimed to determine the effect and mechanical mechanism of spontaneous breathing during mechanical ventilation on oxygenation and lung injury using Beagles dogs mild or moderate acute respiratory distress syndrome (ARDS) model.MethodsAfter inducing mild or moderate ARDS by infusion of oleic acid, Eighteen Beagles dogs were randomly split into Spontaneous breathing group (BIPAPSB, n = 6), and Complete muscle paralysis group (BIPAPPC, n = 6),Six Beagles without ventilator support comprised the control group. Both groups were ventilated for 8 h under BIPAP mode. High-pressure was titrated TV to 6 ml/kg. A multi-pair esophageal balloon electrode catheter was used to measure respiratory mechanics and electromyogram. End-expiratory lung volume (EELV), gas exchange and respiratory variables were recorded in the process of mechanical ventilation. The contents of Interleukin (IL)-6 and IL-8 in lung tissue were measure using qRT-PCR. Besides, lung injury score was calculated in the end of mechanical ventilation.ResultsBased on the comparable setting of ventilator, BIPAPSB group exhibited higher safety peak transpulmonary pressure, abdominal pressure, EELV and P/F(PaO2/FiO2) than BIPAPPC group, whereas mean transpulmonary pressure, the mRNA levels of the IL-6 and IL-8 in the lung tissues and lung injury score in BIPAPSB group were lower than those in BIPAPPC group.ConclusionIn mild to moderate ARDS animal models, during mechanical ventilation, SB may improve respiratory function and reduce ventilator-induced lung injury. The mechanism may be that spontaneous inspiration up-regulates peak transpulmonary pressure and EELV; Spontaneous expiration decreases mean transpulmonary pressure by up-regulating intra-abdominal pressure, thereby reducing stress and strain.

High-frequency oscillatory ventilation guided by transpulmonary pressure in acute respiratory syndrome: an experimental study in pigs

BackgroundRecent clinical studies have not shown an overall benefit of high-frequency oscillatory ventilation (HFOV), possibly due to injurious or non-individualized HFOV settings. We compared conventional HFOV (HFOVcon) settings with HFOV settings based on mean transpulmonary pressures (PLmean) in an animal model of experimental acute respiratory distress syndrome (ARDS).MethodsARDS was induced in eight pigs by intrabronchial installation of hydrochloric acid (0.1 N, pH 1.1; 2.5 ml/kg body weight). The animals were initially ventilated in volume-controlled mode with low tidal volumes (6 ml kg− 1) at three positive end-expiratory pressure (PEEP) levels (5, 10, 20 cmH2O) followed by HFOVcon and then HFOV PLmean each at PEEP 10 and 20.The continuous distending pressure (CDP) during HFOVcon was set at mean airway pressure plus 5 cmH2O. For HFOV PLmean it was set at mean PL plus 5 cmH2O. Baseline measurements were obtained before and after induction of ARDS under volume controlled ventilation with PEEP 5. The same measurements and computer tomography of the thorax were then performed under all ventilatory regimens at PEEP 10 and 20.ResultsCardiac output, stroke volume, mean arterial pressure and intrathoracic blood volume index were significantly higher during HFOV PLmean than during HFOVcon at PEEP 20. Lung density, total lung volume, and normally and poorly aerated lung areas were significantly greater during HFOVcon, while there was less over-aerated lung tissue in HFOV PLmean. The groups did not differ in oxygenation or extravascular lung water index.ConclusionHFOV PLmean is associated with less hemodynamic compromise and less pulmonary overdistension than HFOVcon. Despite the increase in non-ventilated lung areas, oxygenation improved with both regimens. An individualized approach with HFOV settings based on transpulmonary pressure could be a useful ventilatory strategy in patients with ARDS. Providing alveolar stabilization with HFOV while avoiding harmful distending pressures and pulmonary overdistension might be a key in the context of ventilator-induced lung injury.

CORP: Measurement of lung function in small animals.

The measurement of lung function in mice and rats is crucial for understanding how well small animal models of pulmonary disease recapitulate human clinical pathology but brings with it the challenge of making accurate measurements in animals as small as a mouse. Overcoming these challenges can be achieved in a number of ways, each based on a model idealization of how the lung works as a mechanical system. Accordingly, it is important to understand the theoretical basis on which an assessment of lung function rests to interpret experimental measurements appropriately. It is also crucial to attend to a number of practical issues that determine the quality of the measurements. The most accurate measurements of lung function in small animals are provided by the forced oscillation technique that provides lung resistance and elastance and its multifrequency generalization known as impedance. Measurement quality is maximized when the greatest possible degree of control is exerted over the amplitude and frequency with which air is oscillated in and out of the lungs, the mean or end-expiratory transpulmonary pressure pertaining to when the oscillations are applied, and the immediate past volume history of the lungs. It is also crucial that no spontaneous breathing efforts occur during the measurement period. Finally, there is no substitute for the skill in animal handling and surgical preparation that comes with practice; such a skill should be in place before embarking on any important series of experiments.

Effects of pressure support and pressure-controlled ventilation on lung damage in a model of mild extrapulmonary acute lung injury with intra-abdominal hypertension.

Intra-abdominal hypertension (IAH) may co-occur with the acute respiratory distress syndrome (ARDS), with significant impact on morbidity and mortality. Lung-protective controlled mechanical ventilation with low tidal volume and positive end-expiratory pressure (PEEP) has been recommended in ARDS. However, mechanical ventilation with spontaneous breathing activity may be beneficial to lung function and reduce lung damage in mild ARDS. We hypothesized that preserving spontaneous breathing activity during pressure support ventilation (PSV) would improve respiratory function and minimize ventilator-induced lung injury (VILI) compared to pressure-controlled ventilation (PCV) in mild extrapulmonary acute lung injury (ALI) with IAH. Thirty Wistar rats (334±55g) received Escherichia coli lipopolysaccharide intraperitoneally (1000μg) to induce mild extrapulmonary ALI. After 24h, animals were anesthetized and randomized to receive PCV or PSV. They were then further randomized into subgroups without or with IAH (15 mmHg) and ventilated with PCV or PSV (PEEP = 5cmH2O, driving pressure adjusted to achieve tidal volume = 6mL/kg) for 1h. Six of the 30 rats were used for molecular biology analysis and were not mechanically ventilated. The main outcome was the effect of PCV versus PSV on mRNA expression of interleukin (IL)-6 in lung tissue. Regardless of whether IAH was present, PSV resulted in lower mean airway pressure (with no differences in peak airway or peak and mean transpulmonary pressures) and less mRNA expression of biomarkers associated with lung inflammation (IL-6) and fibrogenesis (type III procollagen) than PCV. In the presence of IAH, PSV improved oxygenation; decreased alveolar collapse, interstitial edema, and diffuse alveolar damage; and increased expression of surfactant protein B as compared to PCV. In this experimental model of mild extrapulmonary ALI associated with IAH, PSV compared to PCV improved lung function and morphology and reduced type 2 epithelial cell damage.

Comparison between effects of pressure support and pressure-controlled ventilation on lung and diaphragmatic damage in experimental emphysema.

BackgroundIn patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema.MethodsEmphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks. Control animals received saline under the same protocol. Eight weeks after first instillation, control and emphysema rats were randomly assigned to PCV (n = 6/each) or PSV (n = 6/each) under protective tidal volume (6 ml/kg) for 4 h. Non-ventilated control and emphysema animals (n = 6/group) were used to characterize the model and for molecular biology analysis. Cardiorespiratory function, lung histology, diaphragm ultrastructure alterations, extracellular matrix organization, diaphragmatic proteolysis, and biological markers associated with pulmonary inflammation, alveolar stretch, and epithelial and endothelial cell damage were assessed.ResultsEmphysema animals exhibited cardiorespiratory changes that resemble human emphysema, such as increased areas of lung hyperinflation, pulmonary amphiregulin expression, and diaphragmatic injury. In emphysema animals, PSV compared to PCV yielded: no changes in gas exchange; decreased mean transpulmonary pressure (Pmean,L), ratio between inspiratory and total time (Ti/Ttot), lung hyperinflation, and amphiregulin expression in lung; increased ratio of pulmonary artery acceleration time to pulmonary artery ejection time, suggesting reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm. Amphiregulin correlated with Pmean,L (r = 0.99, p < 0.0001) and hyperinflation (r = 0.70, p = 0.043), whereas Ti/Ttot correlated with hyperinflation (r = 0.81, p = 0.002) and Pmean,L (r = 0.60, p = 0.04).ConclusionsIn the model of elastase-induced emphysema used herein, PSV reduced lung damage and improved cardiac function when compared to PCV, but worsened diaphragmatic injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-016-0107-0) contains supplementary material, which is available to authorized users.

Higher Levels of Spontaneous Breathing Induce Lung Recruitment and Reduce Global Stress/Strain in Experimental Lung Injury

Spontaneous breathing (SB) in the early phase of the acute respiratory distress syndrome is controversial. Biphasic positive airway pressure/airway pressure release ventilation (BIPAP/APRV) is commonly used, but the level of SB necessary to maximize potential beneficial effects is unknown. Experimental acute respiratory distress syndrome was induced by saline lung lavage in anesthetized and mechanically ventilated pigs (n = 12). By using a Latin square and crossover design, animals were ventilated with BIPAP/APRV at four different levels of SB in total minute ventilation (60 min each): (1) 0% (BIPAP/APRV0%); (2) greater than 0 to 30% (BIPAP/APRV>0-30%); (3) greater than 30 to 60% (BIPAP/APRV>30-60%); and (4) greater than 60% (BIPAP/APRV>60%). Gas exchange, hemodynamics, and respiratory variables were measured. Lung aeration was assessed by high-resolution computed tomography. The distribution of perfusion was marked with Ga-labeled microspheres and evaluated by positron emission tomography. The authors found that higher levels of SB during BIPAP/APRV (1) improved oxygenation; (2) decreased mean transpulmonary pressure (stress) despite increased inspiratory effort; (3) reduced nonaerated lung tissue, with minimal changes in the distribution of perfusion, resulting in decreased low aeration/perfusion zones; and (4) decreased global strain (mean ± SD) (BIPAP/APRV0%: 1.39 ± 0.08; BIPAP/APRV0-30%: 1.33 ± 0.03; BIPAP/APRV30-60%: 1.27 ± 0.06; BIPAP/APRV>60%: 1.25 ± 0.04, P < 0.05 all vs. BIPAP/APRV0%, and BIPAP/APRV>60% vs. BIPAP/APRV0-30%). In a saline lung lavage model of experimental acute respiratory distress syndrome in pigs, levels of SB during BIPAP/APRV higher than currently recommended for clinical practice, that is, 10 to 30%, improve oxygenation by increasing aeration in dependent lung zones without relevant redistribution of perfusion. In presence of lung recruitment, higher levels of SB reduce global stress and strain despite an increase in inspiratory effort.

Airway Pressure and Transpulmonary Pressure During High-Frequency Oscillation for Acute Respiratory Distress Syndrome

High-frequency oscillation (HFO) is used for the treatment of refractory hypoxic respiratory failure. To demonstrate that the mean transpulmonary pressure (PL) cannot be inferred from mean airway pressure (mPaw). In seven patients already undergoing HFO for refractory acute respiratory distress syndrome, esophageal pressure (Pes) was measured using an esophageal balloon catheter. Pleural pressure (Ppl) and PL were calculated from Pes. In the seven patients (mean [± SD] age 59 ± 9 years) treated with HFO at 5 ± 1 Hz and amplitude 75 ± 10 cmH2O, the mPaw was 27 ± 6 cmH2O, Ppl was 9 ± 6 cmH2O and PL was 18 ± 11 cmH2O. Successful catheter placement and measurement of Pes occurred in 100% of subjects. There was no correlation between PL and mPaw. The majority of subjects required hemodynamic support during the use of HFO; the frequency and degree of support during the study period was no different than that before the study. The present report is the first to describe measuring Pes and calculating Ppl during HFO for acute respiratory distress syndrome. While both current guidelines and recent trials have titrated treatment based on mPaw and oxygenation, there is wide variability in PL during HFO and PL cannot be predicted from mPaw.

Impact of Ventilation Frequency and Parenchymal Stiffness on Flow and Pressure Distribution in a Canine Lung Model

To determine the impact of ventilation frequency, lung volume, and parenchymal stiffness on ventilation distribution, we developed an anatomically-based computational model of the canine lung. Each lobe of the model consists of an asymmetric branching airway network subtended by terminal, viscoelastic acinar units. The model allows for empiric dependencies of airway segment dimensions and parenchymal stiffness on transpulmonary pressure. We simulated the effects of lung volume and parenchymal recoil on global lung impedance and ventilation distribution from 0.1 to 100 Hz, with mean transpulmonary pressures from 5 to 25 cm H2O. With increasing lung volume, the distribution of acinar flows narrowed and became more synchronous for frequencies below resonance. At higher frequencies, large variations in acinar flow were observed. Maximum acinar flow occurred at first antiresonance frequency, where lung impedance achieved a local maximum. The distribution of acinar pressures became very heterogeneous and amplified relative to tracheal pressure at the resonant frequency. These data demonstrate the important interaction between frequency and lung tissue stiffness on the distribution of acinar flows and pressures. These simulations provide useful information for the optimization of frequency, lung volume, and mean airway pressure during conventional ventilation or high frequency oscillation (HFOV). Moreover our model indicates that an optimal HFOV bandwidth exists between the resonant and antiresonant frequencies, for which interregional gas mixing is maximized.

Experience and intermediate-term results using the Contegra(R) heterograft for right ventricular outflow reconstruction in adults

The Contegra bioprosthesis (valved heterologous bovine jugular vein) is used for reconstruction of the right ventricular outflow tract (RVOT) in congenital heart malformations and pulmonary valve replacement in different settings. Compared to pulmonary homografts, the Contegra conduit is readily available 'on the shelf'. So far, its use was mainly described in children. The aim of this study is to evaluate the feasibility and the outcome of Contegra graft implantation in the adult. Between November 1999 and December 2007, a total of 32 Contegra grafts were implanted in 31 patients (24 men and 7 women), with a mean age of 35.7+/-10.5 years (range 18-54 years). All operations have been completed through median sternotomy with cardiopulmonary bypass. Indications included: Ross procedure for aortic valve disease (n=22); re-operation of corrected Fallot-tetralogy (n=5); isolated pulmonary valve disease (n=2); re-operation of double outlet right ventricle (DORV) (n=1); pulmonary stenosis in congenital dilated cardiomyopathy (DCM) (n=1). Conduit sizes included 22 mm (n=31), 20 mm (n=1). There was no hospital mortality and no valved conduit related early morbidity. In the median follow-up of 38 months (range 1-99 months) of 28 patients there was one late death, not conduit related (total mortality 3.6%). Re-operation for symptomatic graft stenosis was realised in two patients, 7 and 16 months after primo-implantation, corresponding to graft related late morbidity of 7.1%. In this small review of 32 operations using the Contegra graft for RVOT reconstruction in adult cardiac surgery for different indications, we observed good postoperative mid-term results concerning conduit function. Mean transpulmonary pressure gradients remain low (13.3+/-6.6 mmHg postoperative, 14.5+/-7.9 mmHg at follow-up). The use of the Contegra graft seems to be a good alternative to the homograft with low operative mortality and morbidity. Long-term outcome data are not available and further investigations must be performed to evaluate results.

Impact of microvascular circulation on peripheral lung stability.

The involvement of pulmonary circulation in the mechanical properties was studied in isolated rat lungs. Pulmonary input impedance (ZL) was measured at a mean transpulmonary pressure (Ptpmean) of 2 cmH2O before and after physiological perfusion with either blood or albumin. In these lungs and in a group of unperfused lungs, ZL was also measured at Ptpmean values between 1 and 8 cmH2O. Airway resistance (Raw) and parenchymal damping (G) and elastance (H) were estimated from ZL. End-expiratory lung volume (EELV) was measured by immersion before and after blood perfusion. The orientation of the elastin fibers relative to the basal membrane was assessed in additional unperfused and blood-perfused lungs. Pressurization of the pulmonary capillaries significantly decreased H by 31.5 +/- 3.7% and 18.7 +/- 2.7% for blood and albumin, respectively. Perfusion had no effect on Raw but markedly altered the Ptpmean dependences of G and H < 4 cmH2O, with significantly lower values than in the unperfused lungs. At a Ptpmean of 2 cmH2O, EELV increased by 31 +/- 11% (P = 0.01) following pressurization of the capillaries, and the elastin fibers became more parallel to the basal membrane. Because the organization of elastin fibers results in smaller H values of the individual alveolus, the higher H in the unperfused lungs is probably due to a partial alveolar collapse leading to a loss in lung volume. We conclude that the physiological pressure in the pulmonary capillaries is an important mechanical factor in the maintenance of the stability of the alveolar architecture.

Airway closure and reopening assessed by the alveolar capsule oscillation technique.

An alveolar capsule oscillation technique was used to determine 1) the lobe pressure and volume at which airways close and reopen, 2) the effect of expiration rate on closing volume and pressure, 3) the phase in the breathing cycle at which airway closure occurs, and 4) the site of airway closure. Experiments were conducted in excised dog lobes; closure was detected by an abrupt increase in the input impedance of surfacemounted alveolar capsules. Mean transpulmonary pressure (Ptp) at closure was slightly less than zero (Ptp = -2.3 cmH2O); the corresponding mean reopening pressure was Ptp = 14 cmH2O. The expiration rate varied between 1 and 20% of total lobe capacity per second and had no consistent effect on the closing volume and pressure. When lung volume was cycled up to frequencies of 0.2 Hz, closure generally occurred on expiration rather than inspiration. These observations support the conclusion that mechanical collapse, rather than meniscus formation, is the most likely mechanism producing airway closure in normal excised dog lungs. Analysis of measured acoustic impedances and reopening pressures suggests that closure occurs in the most peripheral airways. Reopening during inspiration was often observed to consist of a series of stepwise decreases in capsule impedance, indicating a sequence of opening events.

Does Airway Pressure Release Ventilation Alter Lung Function After Acute Lung Injury?

During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. Experimental, subject-controlled, randomized crossover investigation. Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. Ten pigs of either sex. Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics.

Control of bronchomotor tone during perinatal development in sheep

To characterize the perinatal maturation of the cholinergic control of the airways, we compared the effects of bilateral cervical vagotomy and supramaximal vagal stimulation on the airway resistances of 7 premature (130-133 days of gestation), 11 term newborn, and 9 9-wk-old lambs anesthetized with pentobarbital. Resistances were partitioned between central and peripheral airways with catheters placed retrogradely into peripheral bronchi and capsules attached to the pleural surface in communication with subpleural air spaces. The central and peripheral airway resistances of premature and term newborn lambs and the peripheral resistance of 9-wk-old lambs decreased after vagotomy but only when the lungs were ventilated with small tidal volumes at mean transpulmonary pressures < or = 7.5 cmH2O. Vagotomy caused smaller absolute changes in central airway resistance than vagal stimulation. In contrast, both vagotomy and vagal stimulation produced similar absolute changes in peripheral airway resistance, indicating that resting cholinergic outflow is preferentially distributed to the peripheral airways even at the earlier ages. The effects of vagal stimulation on airway resistance were prevented by atropine. Our results prove that a resting bronchomotor tone can be present in both central and peripheral airways before the term of gestation in sheep. This tone depends on the activity of cholinergic fibers in the vagus and can be regionally controlled.

Viscoelastic properties of rabbit lung during growth

Viscoelasticity of air-filled isolated lungs of 1–120 day old rabbits was studied at a mean transpulmonary pressure (P1) of 0.65 kPa by measuring: (1) their stress relaxation (SR) following step volume changes (ΔV) corresponding to 5% of the vital capacity; (2) their resistance (R1) and elastance (E1) during sinusoidal cycling at 11 frequencies (f) ranging from 0.01 to 0.65 Hz. SR data were analyzed by least-square regression using Hildebrandt's logarithmic model (Hildebrandt, J. (1970) J. Appl. Physiol. 28: 365–372): Δ P1/Δ V = A − B· log( t) whereA is an index of elastance, and B/A is a measure of viscoelasticity. Coefficients A and B were also obtained from R1 and E1 according to: R1 = B/9.2 f and E1 = A + 0.25 B + B· log(2 π f) . Elastance corrected for lung weight increased by 40% between day 1 and days 3–7, and decreased thereafter to reach 30% of its initial value in 120 day old rabbits. B/A ratios also demonstrated an initial rise, followed by a progressive decrease. Values of B/A computed from R1 and E1 were similar to those derived from SR data in day old rabbits, but were 20–30% larger in order animals, which indicates the presence of an additional rate-independent dissipation during flow. Total internal dissipation during cycling varied little with frequency; it was largest in 3–37 day old animals where it represented 20% of the stored elastic energy.

Nonlinearity and harmonic distortion of dog lungs measured by low-frequency forced oscillations

The nonlinearity of lung tissues and airways was studied in six anesthetized and paralyzed open-chest dogs by means of 0.1-Hz sinusoidal volume forcing at mean transpulmonary pressures (Ptp) of 5 and 10 cmH2O. Lung resistance (RL) and elastance (EL) were determined in a 32-fold range (15-460 ml) of tidal volume (VT), both by means of spectrum analysis at the fundamental frequency and with conventional time-domain techniques. Alveolar capsules were used to separate the tissue and airway properties. A very small amplitude dependence was found: with increasing VT, the frequency-domain estimates of RL decreased by 5.3 and 14%, whereas EL decreased by 20 and 22% at Ptp = 5 and 10 cmH2O, respectively. The VT dependences of the time-domain estimates of RL were higher: 10.5 and 20% at Ptp = 5 and 10 cmH2O, respectively, whereas EL remained the same. The airway resistance increased moderately with flow amplitude and was smaller at the higher Ptp level. Analysis of the harmonic distortions of airway opening pressure and the alveolar pressures indicated that nonlinear harmonic production is moderate even at the highest VT and that VT dependence is homogeneous throughout the tissues. In three other dogs it was demonstrated that VT dependences of RL and EL were similar in situ and in isolated lungs at both Ptp levels.

Modeling of low-frequency pulmonary impedance in dogs

The mechanical impedance of the lungs (ZL) was measured in open-chest dogs with small-amplitude pseudorandom volume oscillations between 0.125 and 5 Hz, at mean transpulmonary pressures (Ptp) of 0.2, 0.4, and 0.8 kPa. At the lowest frequencies, the pulmonary resistance showed a marked negative frequency dependence and mirrored the changes in the reactance with altered Ptp. The ZL data were evaluated on the basis of two models, each containing the same airway compartment with a resistance and an inertance. The tissue impedance (Zti) in model 1 was represented with two compliances and a resistance (L. E. Mount. J. Physiol. Lond. 127: 157-167, 1955), whereas in model 2 a two-parameter formulation implying rate-independent dissipated work and frequency-dependent elastance (J. Hildebrandt. J. Appl. Physiol. 28: 365-372, 1970) was employed. The estimation of model parameters showed that model 2 was superior to model 1 in both fitting performance and parameter insensitivity to weighting in the fitting criterion. The model 2 coefficients of damping and elastance, characterizing the real and imaginary parts of Zti, respectively, depended on the lung distension and were closely correlated. Although ZL exhibited a slight dependence on the peak-to-peak volume excursion, at a given oscillatory volume no inconsistency with linear tissue viscoelasticity was detected.

Role of lung biopsy in patients undergoing a modified Fontan procedure

Fifty-six patients undergoing a modified Fontan procedure from 1977 to 1985 had lung tissue available from the perioperative period (n = 51) or recent palliative procedure (n = 5) (37 biopsy, 12 autopsy, 7 biopsy and autopsy). Twenty-six patients had tricuspid atresia, and 30 had other causes of functional univentricular heart. Pulmonary arterial structure was classified by both the Heath-Edwards and morphometric scales. Biopsy and autopsy grades were identical except for a minor difference in Heath-Edwards scale in one case. Elevated preoperative mean pulmonary artery pressure (greater than 15 mm Hg) was associated with medial hypertrophy (p = 0.04), although six patients with normal pulmonary artery pressure had medial hypertrophy and six patients with mean pulmonary artery pressure greater than 15 mm Hg did not have medial hypertrophy. Medial hypertrophy was a possible risk factor in patients with univentricular heart: Patients with medial hypertrophy had a ninefold greater risk of death (p = 0.08). Controlling for confounding variables did not alter this result (0.06 less than or equal to p less than or equal to 0.10). Medial hypertrophy was not a risk factor for death in patients with tricuspid atresia: Four had this feature and each survived. Four patients with tricuspid atresia died and none had medial hypertrophy. A mean transpulmonary pressure gradient was measured on the first postoperative day in 45 patients. In patients with medial hypertrophy there was a trend toward a higher gradient (p = 0.13). All patients with medial hypertrophy who had this measurement (n = 9) had a transpulmonary pressure gradient of 7 mm Hg or greater, whereas this was true in only 18 of 36 without medial hypertrophy (p = 0.007). On the basis of an evaluation of medial hypertrophy, we conclude that biopsy does not aid in selection of patients with tricuspid atresia for a Fontan procedure; its role in patients with univentricular heart is uncertain.

Pulmonary and systemic vascular response to promethazine in conscious lambs.

Promethazine is an antihistamine commonly used for sedation in clinical pediatric medicine. We studied the cardiovascular effects of promethazine in normoxic, conscious, chronically instrumented neonatal lambs. Eight lambs received 1.3 mg/kg of promethazine intravenously (i.v.) while at rest. In all lambs, promethazine led to elevations of pulmonary vascular resistance, mean pulmonary arterial pressure, mean transpulmonary pressure, mean left atrial pressure, and the ratio of pulmonary-to-systemic vascular resistance. In addition, five (63%) of the lambs demonstrated an increase in mean systemic arterial pressure and systemic vascular resistance to promethazine. A subgroup of three lambs, which tended to be younger, failed to demonstrate the systemic vascular response to promethazine. Promethazine given i.v. has important cardiovascular effects. We hypothesize that promethazine used for sedation before cardiac catheterization in children may alter subsequent hemodynamic observations.

Unilateral diaphragmatic paralysis inhibits postnatal lung growth in the piglet.

To test the hypothesis that regional growth of lung parenchyma depends on regional distending pressure, left cervical phrenectomy was done in ten 2-month-old piglets. The unilateral diaphragmatic paralysis reduced mean transpulmonary pressure in the left hemithorax from 5.5 +/- 1.0 (means +/- SD) to 2.5 +/- 1.2 cm H2O (p less than 0.01, n = 5). When five of the piglets were killed 48 h later, wet lung weight, total protein content, and nucleic acid content did not differ from values in the five sham operated controls. The five remaining phrenectomized piglets were compared to their five sham-operated controls 7 days after surgery. Wet weight of the left lung was reduced by 29% (p less than 0.01) and DNA content was reduced by 18% (p less than 0.05). Wet weight of the right lung, contralateral to the paralyzed hemidiaphragm, was reduced by 11% (p less than 0.05). At this time, body weight, bilateral transpulmonary pressure, and ratios of total protein/DNA and RNA/DNA in lung tissue did not differ from the sham-operated controls. These results suggest that regional growth of lung parenchyma by cell proliferation adjusted to changes in regional transpulmonary pressure caused by the unilateral phrenectomy.