Maldistribution Of Pulmonary Blood Flow Research Articles

Calculating Relative Lung Perfusion Using Fluoroscopic Sequences and Image Analysis: The Fluoroscopic Flow Calculator.

Maldistribution of pulmonary blood flow in patients with congenital heart disease impacts exertional performance and pulmonary artery growth. Currently, measurement of relative pulmonary perfusion can only be performed outside the catheterization laboratory. We sought to develop a tool for measuring relative lung perfusion using readily available fluoroscopy sequences. A retrospective cohort study was conducted on patients with conotruncal anomalies who underwent lung perfusion scans and subsequent cardiac catheterizations between 2011 and 2022. Inclusion criteria were nonselective angiogram of pulmonary vasculature, oblique angulation ≤20°, and an adequate view of both lung fields. A method was developed and implemented in 3D Slicer's SlicerHeart extension to calculate the amount of contrast that entered each lung field from the start of contrast injection and until the onset of levophase. The predicted perfusion distribution was compared with the measured distribution of pulmonary blood flow and evaluated for correlation, accuracy, and bias. In total, 32% (79/249) of screened studies met the inclusion criteria. A strong correlation between the predicted flow split and the measured flow split was found (R2=0.83; P<0.001). The median absolute error was 6%, and 72% of predictions were within 10% of the true value. Bias was not systematically worse at either extreme of the flow distribution. The prediction was found to be more accurate for either smaller and younger patients (age 0-2 years), for right ventricle injections, or when less cranial angulations were used (≤20°). In these cases (n=40), the prediction achieved R2=0.87, median absolute error of 5.5%, and 78% of predictions were within 10% of the true flow. The current study demonstrates the feasibility of a novel method for measuring relative lung perfusion using conventional angiograms. Real-time measurement of lung perfusion at the catheterization laboratory has the potential to reduce unnecessary testing, associated costs, and radiation exposure. Further optimization and validation is warranted.

Abstract 11609: Developing a Novel Method for Measuring Relative Lung Perfusion at the Catheterization Laboratory

Background: Maldistribution of pulmonary blood flow (Qp) is common in patients with congenital heart disease and is associated with worse clinical outcomes. Currently, measurement of Qp-split can only be performed outside the catheterization laboratory, using either lung perfusion scans or cardiac magnetic resonance imaging. Aim: We sought to develop and evaluate a tool for measuring Qp-split using readily available fluoroscopy sequences. Methods: A retrospective cohort study of patients with conotruncal anomalies who underwent perfusion scan and subsequent cardiac catheterization. Inclusion criteria were non-selective angiogram of pulmonary vasculature, oblique angulation ≤20°, and an adequate view of both lung fields. A method was developed and implemented in 3D Slicer to calculate the amount of contrast that entered each lung field from the start of contrast-injection and until the onset of levophase. The predicted perfusion distribution was compared to the distribution measured by lung scan. Results: In total 32% (79/249) of screened studies met inclusion criteria. There was strong correlation between the predicted Qp-split and the measured Qp-split (R 2 =0.83, p&lt;0.001) with median absolute error (MAE) of 6%. Bias was not systematically worse at either extreme of flow distribution. Factors associated with better prediction were smaller BSA, younger age, right ventricle (vs. pulmonary artery) angiograms, and cranial angulations ≤20°. In cases with one or more of these conditions (n=40), the prediction achieved R 2 =0.87, MAE of 5.5%, and 78% of predictions were within 10% of true flow. Conclusions: Data from conventional angiograms can be used to provide accurate real-time measurement of relative perfusion of the left and right lungs. This has the potential to reduce unnecessary testing, associated costs, and radiation exposure.

The VE/VCO2 slope: A useful tool to evaluate the physiological status of children with congenital heart disease

Cardio-pulmonary exercise test (CPET) is becoming a key examination to assess physical capacity and disease severity in paediatric cardiology. The VE/VCO 2 slope has been increasingly used as a surrogate marker for morbidity and mortality in adult heart failure, pulmonary arterial hypertension and for adult patients with CHD. Nevertheless, the use of the VE/VCO 2 slope in children remains limited in the absence of reference values and clearly identified clinical determinants. This study aimed to compare the VE/VCO 2 slope in a paediatric cohort with CHD to that of age- and gender-adjusted healthy controls. We also intended to identify the clinical and CPET variables associated with VE/VCO 2 slope in this population. This cross-sectional study was carried out between November 2010 and September 2015 in two tertiary care paediatric cardiology reference centres. A total of 700 children were enrolled (399 CHD and 301 healthy controls). The mean VE/VCO 2 slope was significantly higher in CHD than in controls (31.6 ± 4.8 vs. 29.3 ± 4.8; P < 0.001). When considering CHD sub-groups, the VE/VCO 2 slope was impaired in single ventricle, complex anomalies of ventriculo-arterial connections, anomalies of the atrioventricular junctions and valves. The VE/VCO 2 slope according to the CHD physiological status was illustrated in the Fig. 1 , it was higher in children with significant pulmonary regurgitation, tricuspid regurgitation, right ventricular hypertension and right ventricle outflow tract (RVOT) obstacle. In the CHD group, VE/VCO 2 slope increase was associated with BMI, the presence of a RVOT obstacle, the number of cardiac catheter procedures, as well as low age, FVC, tidal volume, and PetCO2 ( Fig. 1 ). Increased VE/VCO 2 slope was predominantly in children with single ventricle and/or residual right heart abnormalities suggesting that maldistribution of pulmonary blood flow during exercise is an important CHD-unique determinant of VE/VCO 2 slope.

The VE/VCO2 slope: A useful tool to evaluate the physiological status of children with congenital heart disease

Cardio-pulmonary exercise test (CPET) is becoming a key examination to assess physical capacity and disease severity in paediatric cardiology. The VE/VCO2 slope has been increasingly used as a surrogate marker for morbidity and mortality in adult heart failure, pulmonary arterial hypertension and for adult patients with CHD. Nevertheless, the use of the VE/VCO2 slope in children remains limited in the absence of reference values and clearly identified clinical determinants. This study aimed to compare the VE/VCO2 slope in a paediatric cohort with CHD to that of age- and gender-adjusted healthy controls. We also intended to identify the clinical and CPET variables associated with VE/VCO2 slope in this population. This cross-sectional study was carried out between November 2010 and September 2015 in two tertiary care paediatric cardiology reference centres. A total of 700 children were enrolled (399 CHD and 301 healthy controls). The mean VE/VCO2 slope was significantly higher in CHD than in healthy subjects (31.6 ± 4.8 vs. 29.3 ± 4.8; P < 0.001). When considering CHD sub-groups, the VE/VCO2 slope was impaired in single ventricle, complex anomalies of ventriculo-arterial connections, anomalies of the atrioventricular junctions and valves. The VE/VCO2 slope according to the CHD physiological status was illustrated in the Fig. 1, it was higher in children with significant pulmonary regurgitation, tricuspid regurgitation, right ventricular hypertension and right ventricle outflow tract (RVOT) obstacle. In the CHD group, VE/VCO2 slope increase was associated with BMI, the presence of a RVOT obstacle, the number of cardiac catheter procedures, as well as low age, FVC, tidal volume, and PetCO2 (Fig. 1). Increased VE/VCO2 slope was predominantly in children with single ventricle and/or residual right heart abnormalities suggesting that maldistribution of pulmonary blood flow during exercise is an important CHD-unique determinant of VE/VCO2 slope.

Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Guideline-Driven Care Should Be Our Natural Reflex.

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The V̇e/V̇co2 slope: a useful tool to evaluate the physiological status of children with congenital heart disease.

Cardiopulmonary exercise test (CPET) is becoming a key examination to assess physical capacity and disease severity in pediatric cardiology. The V̇e/V̇co2 slope has been increasingly used as a surrogate marker for morbidity and mortality in adult heart failure, pulmonary arterial hypertension, and for adult patients with congenital heart disease (CHD). Nevertheless, the use of the V̇e/V̇co2 slope in children remains limited in the absence of reference values and clearly identified clinical determinants. This study aimed to compare the V̇e/V̇co2 slope in a pediatric cohort with CHD to that of age- and gender-adjusted healthy controls. We also intended to identify the clinical and CPET variables associated with V̇e/V̇co2 slope in this population. This cross-sectional study was carried out between November 2010 and September 2015 in two tertiary care pediatric cardiology reference centers. A total of 700 children were enrolled (399 CHD and 301 healthy controls). The mean V̇e/V̇co2 slope was significantly higher in the CHD subjects than in healthy subjects (31.6 ± 4.8 vs. 29.3 ± 4.8; P < 0.001). The V̇e/V̇co2 slope was higher in children with significant pulmonary regurgitation, tricuspid regurgitation, right ventricular hypertension, and right ventricle outflow tract (RVOT) obstacle. In the CHD group, V̇e/V̇co2 slope increase was associated with body mass index, the presence of a RVOT obstacle, the number of cardiac catheter procedures, as well as low age, forced vital capacity, tidal volume, and [Formula: see text]. Increased V̇e/V̇co2 slope was predominantly in children with single ventricle and/or residual right heart abnormalities, suggesting that maldistribution of pulmonary blood flow during exercise is an important CHD-unique determinant of V̇e/V̇co2 slope.NEW & NOTEWORTHY Using V̇e/V̇co2 slope is useful for children with congenital heart disease. V̇e/V̇co2 slope is sensitive to pulmonary blood flow maldistribution during exercise, this concerns congenital heart disease with pulmonary regurgitation, tricuspid regurgitation, right ventricular hypertension, and right ventricle outflow tract obstacle. V̇e/V̇co2 slope is a good parameter to follow single ventricles and right heart residual lesions (tetralogy of Fallot; pulmonary atresia; truncus arteriosus…).

Balloon Angioplasty and Stenting for Unilateral Branch Pulmonary Artery Stenosis Improve Exertional Performance

ObjectivesThis study sought to determine whether pulmonary artery intervention in patients with unilateral proximal pulmonary artery stenosis (PAS) improves exercise capacity, abnormal ventilatory response to exercise, and symptoms. BackgroundStenosis of the branch pulmonary arteries results in pulmonary blood flow maldistribution (PBFM). The resulting ventilation–perfusion mismatch is associated with an increased ventilatory response to exercise and decreased exercise capacity. It is unclear if technical success in relieving branch PAS translates to clinical improvement in exercise capacity and ventilatory response. MethodsTwenty patients with biventricular circulation and a minimum 10% PBFM who underwent transcatheter relief of PAS were enrolled in a multi-institutional prospective cohort study. Pre- and post-procedure assessment of the degree of PBFM, exercise capacity, ventilatory response to exercise, and subjective assessment of breathlessness were collected and analyzed. ResultsTechnical success was achieved in all patients with significant angiographic improvement in minimal lumen diameter (p = 0.001) and peak gradient (p = 0.001). Median PBFM improved (19.5% [range 12.0% to 31.0%] before vs. 7.0% [range 0% to 33.0%] after; p = 0.003). Exercise capacity was low at baseline and improved significantly post-intervention; percent predicted peak oxygen consumption improved from 70% (range 45% to 96%) to 83% (range 47% to 121%) (p = 0.02). Percent predicted oxygen pulse improved (p = 0.02). Ventilatory response to exercise improved; ventilatory equivalent of carbon dioxide slope post-intervention decreased to 29.3 versus 32.5 pre-intervention (p = 0.01). Subjective assessment of dyspnea improved. Five patients with minimal improvement in PBFM also showed minimal improvement in exercise parameters. ConclusionsSuccessful relief of unilateral branch PAS results in significant improvements in exercise capacity, ventilatory efficiency, and symptoms.

Maldistribution of pulmonary blood flow in patients after the Fontan operation is associated with worse exercise capacity

BackgroundMaldistribution of pulmonary artery blood flow (MPBF) is a potential complication in patients who have undergone single ventricle palliation culminating in the Fontan procedure. Cardiovascular magnetic resonance (CMR) is the best modality that can evaluate MPBF in this population. The purpose of this study is to identify the prevalence and associations of MPBF and to determine the impact of MPBF on exercise capacity after the Fontan operation.MethodsThis retrospective single-center study included all patients after Fontan operation who had maximal cardiopulmonary exercise test (CPET) and CMR with flow measurements of the branch pulmonary arteries. MPBF was defined as > 20% difference in branch pulmonary artery flow. Exercise capacity was measured as percent of predicted oxygen consumption at peak exercise (% predicted VO2). Linear and logistic regression models were used to determine univariate and multivariable predictors of exercise capacity and correlates of MPBF, respectively.ResultsA total of 147 patients who had CMR between 1999 and 2017 were included (median age at CMR 21.8 years [interquartile range (IQR) 16.5–30.6]) and the median time between CMR and CPET was 2.8 months [IQR 0–13.8]. Fifty-three patients (36%) had MPBF (95% CI 29–45%). The mean % predicted VO2 was 63 ± 16%. Patients with MPBF had lower mean % predicted VO2 compared to patients without MPBF (60 ± 14% versus 65 ± 16%, p = 0.04). On multivariable analysis, a lower % predicted VO2 was independently associated with longer time since Fontan, higher ventricular mass-to-volume ratio, and MPBF. On multivariable analysis, only compression of the branch pulmonary arteries by the ascending aorta or aortic root was associated with MPBF (OR 6.5, 95% CI 5.6–7.4, p < 0.001).ConclusionIn patients after the Fontan operation, MPBF is common and is independently associated with lower exercise capacity. MPBF was most likely to be caused by pulmonary artery compression by the aortic root or the ascending aorta. This study identifies MPBF as an important risk factor and as a potential target for therapeutic interventions in this fragile patient population.

Systemic rapamycin to prevent in-stent stenosis in peripheral pulmonary arterial disease: early clinical experience.

We have taken a novel approach using oral rapamycin - sirolimus - as a medical adjunct to percutaneous therapy in patients with in-stent stenosis and high risk of right ventricular failure. Peripheral pulmonary artery stenosis can result in right ventricular hypertension, dysfunction, and death. Percutaneous pulmonary artery angioplasty and stent placement acutely relieve obstructions, but patients frequently require re-interventions due to re-stenosis. In patients with tetralogy of Fallot or arteriopathy, the problem of in-stent stenosis contributes to the rapidly recurrent disease. Rapamycin was administered to 10 patients (1.5-18 years) with peripheral pulmonary stenosis and in-stent stenosis and either right ventricular hypertension, pulmonary blood flow maldistribution, or segmental pulmonary hypertension. Treatment was initiated around the time of catheterisation and continued for 1-3 months. Potential side-effects were monitored by clinical review and blood tests. Target serum rapamycin level (6-10 ng/ml) was accomplished in all patients; eight of the nine patients who returned for clinically indicated catheterisations demonstrated reduction in in-stent stenosis, and eight of the 10 patients experienced no significant side-effects. Among all, one patient developed diarrhoea requiring drug discontinuation, and one patient experienced gastrointestinal bleeding while on therapy that was likely due to an indwelling feeding tube and this patient tolerated rapamycin well following tube removal. Our initial clinical experience supports that patients with peripheral pulmonary artery stenosis can be safely treated with rapamycin. Systemic rapamycin may provide a novel medical approach to reduce in-stent stenosis.

Exercise Testing and Training in Children With Congenital Heart Disease

The primary function of the cardiopulmonary system is to provide blood flow (and oxygen) in quantities sufficient to support the metabolic needs of the body. The capacity of the cardiopulmonary system to fulfill this function is maximally stressed when an individual's metabolic rate is increased, a condition that occurs most commonly during physical activity/exercise. A number of physiological changes accompany and facilitate the accommodation of the circulatory system to the hemodynamic demands of exercise (Figure 1). In normal individuals, these changes (which during upright exercise include a tripling of the resting heart rate, a >60% reduction in systemic and pulmonary vascular resistance, and a >50% increase in stroke volume) can ultimately produce a >5-fold increase in cardiac output. The increase in cardiac output is accompanied by enhanced ventricular preload (as the ventricles move up their Starling curves to accommodate the increased workload), a doubling of systolic and mean pulmonary artery pressures (most of the increase in pulmonary artery pressures is due to the concomitant rise in left-sided filling pressures; the increase in transpulmonary pressure gradient is relatively small), and a more modest increase in systemic arterial pressures.1,–,4 Figure 1. Some of the physiological changes that accompany and facilitate the accommodation of the circulatory system to the hemodynamic demands of exercise. RAp indicates right atrial pressure; LAp, left atrial pressure; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; PAp, pulmonary artery pressure; and AOp, aortic pressure. Congenital heart disease (CHD) may, in a variety of ways and to a variable extent, adversely affect these hemodynamic adaptations. For instance, patients with a Fontan procedure lack a pulmonary ventricle. They therefore cannot increase their pulmonary blood flow and pressures normally (and consequently cannot maintain their ventricular preload and systemic blood flow) during exercise.5 Patients with tetralogy of Fallot and …

Inhaliertes Stickstoffmonoxid zur Behandlung refraktärer Hypoxämie bei ARDS–Patienten

The acute respiratory distress syndrome (ARDS) is characterized by a maldistribution of pulmonary blood flow towards non-ventilated atelectatic lung areas being the main reason for intrapulmonary right-to-left shunt with the consequence of severe arterial hypoxemia. The application of inhaled nitric oxide (iNO) is a therapeutic option to selectively influence pulmonary blood flow in order to improve arterial oxygenation and to decrease pulmonary artery pressure without relevant systemic side effects. Although randomized controlled trials demonstrated no survival benefit in patient populations covering the entire severity range of acute lung injury, iNO represents a feasible rescue treatment for ARDS patients with severe refractory hypoxemia and is, therefore, an important option for ARDS therapy in specialized centers.

Effect of pulmonary artery angioplasty on exercise function after repair of tetralogy of Fallot

The slope of the minute ventilation versus CO2 production relationship (VE/VCO2 slope) is an index of gas exchange efficiency during exercise. In patients with repaired tetralogy of Fallot (rTOF), it correlates negatively with exercise capacity and is one of the best predictors of peak oxygen consumption (VO2). In these patients, the magnitude of the VE/VCO2 slope is related to the severity of pulmonary blood flow maldistribution (PBFM). The purpose of this study was to determine whether, in patients with rTOF, improvements in PBFM after a successful balloon angioplasty procedure (BAP) result in improvements in peak VO2 and gas exchange during exercise. Seventeen patients with rTOF and residual pulmonary artery stenoses referred for BAP were recruited. Exercise tests were performed and PBFM determined before and after BAP. Nine patients (group 1) had a successful BAP (ie, improvement of >5 percentage points in PBFM); 8 did not (group 2). Patients in group 1 had significantly greater improvements in VE/VCO2 slope, peak VO2, and peak oxygen pulse (an index of forward stroke volume at peak exercise) than did patients in group 2. A significant correlation existed between the improvement in PBFM and the decline in the VE/VCO2 slope (r = -0.70, P = .002). Changes in peak oxygen pulse accounted for 89% of the improvement in peak VO2. In these patients, a successful BAP resulted in improved peak VO2 and more efficient gas exchange during exercise. The improvement in peak VO2 appeared to be mediated by an increase in forward stroke volume.

Effect of Pulmonary Artery Stenoses on the Cardiopulmonary Response to Exercise Following Repair of Tetralogy of Fallot

Data from exercise tests, echocardiograms, and lung perfusion scans were analyzed to determine whether the excessive minute ventilation (VE) often encountered among patients with tetralogy of Fallot is due to ventilation-perfusion mismatch secondary to branch pulmonary artery stenoses. Patients with branch PA stenoses had lower peak oxygen consumptions and higher VE during exercise than did patients without stenoses, and a strong correlation existed between the degree of pulmonary blood flow maldistribution on lung perfusion scan and the amount of excessive VE during exercise.

Importance of abnormal lung perfusion in excessive exercise ventilation in chronic heart failure

Whether excessive ventilatory response to exercise is related to the maldistribution of pulmonary blood flow was examined in 23 patients with chronic heart failure and nine age-matched normal subjects. With the use of technetium 99m macroaggregated albumin, the resting distribution of pulmonary blood flow was assessed by the scintigraphic counts ratio of upper to lower lung fields. The ventilatory response to exercise was assessed by the slope of the relationship between minute ventilation and carbon dioxide production during exercise. Eight patients (group A) had slope less than 33, the upper limit of the normal range, and 15 patients had slope of 33 or greater (group B). In group B pulmonary blood flow was distributed more to the upper lung, which made the counts ratio (60%) higher than in normal subjects (34%) or in patients in group A (38%). There was no significant difference in pulmonary flow distribution between normal subjects and patients in group A. In group B tidal volume did not increase during exercise as much as it did in normal subjects and in patients in group A; therefore, the respiratory pattern was rapid and shallow. Although the ratio of physiologic dead space to tidal volume fell by 20% during exercise in normal subjects and by 23% in patients in group A, it failed to decrease in patients in group B (−1%), which indicates a relative increase in dead space respiration during exercise. These data indicate that decreased lung compliance and regional ventilation-perfusion mismatch caused by pulmonary vascular and parenchymal abnormalities would play an important role in the excessive exercise ventilation in chronic heart failure.

Cardiorespiratory response to exercise after the Fontan procedure for tricuspid atresia.

Noninvasive exercise testing was used to assess gas exchange in 13 patients age 6-25 yr who had undergone Fontan procedures for tricuspid atresia, five of whom had preexisting Glenn shunts. The results were compared to 28 age- and sex-matched controls. Oxygen saturation was measured by ear oximetry at rest and after exercise. Ventilation, oxygen consumption (VO2), carbon dioxide production (VCO2), and heart rate were measured during progressive exercise. The ventilatory equivalents for oxygen (VE/VO2) and carbon dioxide (VE/VCO2), mixed expired pCO2 (PECO2) end-tidal pCO2 (PETCO2), and dead space to tidal volume ratio (VD/VT) were determined during steady state exercise on a cycle ergometer. Heart rate was higher for VO2 by 15% (p less than 0.02) and ventilation was higher for both VO2 (by 37%, p less than 0.001) and VCO2 (by 27%, p less than 0.002) in the patients than the controls. Mean VE/VO2 was 35.4 +/- 7.8 (SD) compared to 25.8 +/- 3.1 (p less than 0.001) and mean VE/VCO2 was 41.7 +/- 9.0 compared to 31.6 +/- 4.3 (p less than 0.001). Mean PECO2 was 21.4 +/- 4.4 torr with controls at 27.9 +/- 3.8 (p less than 0.001) and mean PETCO2 was 33.0 +/- 5.3 torr compared to 40.0 +/- 3.3 (p less than 0.001). The patients had a mean oxygen saturation of 92 +/- 5% at rest and abnormal saturation after exercise (87 +/- 9, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

104 RESPONSE TO EXERCISE AFTER FONTAN PROCEDURE

Previous studies demonstrating maldistribution of pulmonary blood flow in patients who had undergone Fontan procedures (FP) predict high physiologic dead space during exercise. We used non-invasive exercise testing to assess gas exchange in 5 patients age 10-19, compared to 11 age and sex matched controls. Oxygen saturation was measured by ear oximetry at rest and after exercise. The ventilatory equivalents for oxygen (Ve/VO2) and carbon dioxide (Ve/VCO2) were measured during progressive exercise and mixed expired pCO2 (PeCO2) and end-tidal pCO2 (PetCO2) were measured during steady state exercise on a cycle ergometer. We obtained the following results: In addition, the patients had a mean oxygen saturation of 89±6% at rest and desaturated further during exercise (81±11, p<0.05). These data show high ventilation for O2 consumption and CO2 production, low expired CO2 concentrations and oxygen desaturation during exercise. The results strongly indicate elevated physiologic dead space and ventilation perfusion mismatch consistent with maldistribution of pulmonary blood flow.

Serial studies of lung volume and VA-Q in hyaline membrane disease.

Extract: Twenty infants with a clinical and radiologic diagnosis of hyaline membrane disease were studied serially by measurement of functional residual capacity (FRC) and arterial and alveolar gradients for O2, CO2, and N2. Nitrogen washouts were determined as well in nine infants. The FRC, alveolar-arterial O2 gradients (AaDo2) in 100% O2, and true shunt (Qs/Qt), which are different ways of quantitating atelectasis and shunt in hyaline membrane disease, were shown to be statistically related. The FRC was below 1.0 ml/cm in all infants when sick and returned to the usual range for gestational age, generally around 15 days. Extensive cardiopulmonary shunting was recorded both at the height of illness and for a considerable time during recovery. However, during recovery, not all of the venous admixture was due to shunt. As maldistribution of ventilation was excluded, the possibility of a diffusion barrier was raised. Alveoli with a high VA/Q were identified by large arterial-alveolar CO2 gradients (aADCO2) both during illness and recovery. This indicates that maldistribution of pulmonary blood flow is an important physiologic abnormality in hyaline membrane disease. Speculation: The FRC was shown to correlate inversely with AaDo2 and Qs/Qt ratios. As a low FRC is the only true unique characteristic of hyaline membrane disease, it is suggested that in the future the disease be defined in terms of the lung volume as well as in terms of the usual clinical and biochemical parameters which appear in other forms of respiratory distress in neonates. Constant positive airway pressure is an attempt to approach treatment from this point of view.