Hospitalization in amyotrophic lateral sclerosis: causes, costs, and outcomes.

OBJECTIVE: As ALS progresses, extensive supportive care is required, including multidisciplinary outpatient care and hospitalization. The authors studied the causes, health care utilization, and outcomes for hospitalized patients with ALS. METHODS: With use of the 1996 Nationwide Inpatient Sample, an administrative database representing 20% of U.S. hospitals, 1,600 hospitalizations in patients with ALS were identified and compared with 5,364,728 non-ALS hospitalizations. RESULTS: The most common concurrent diagnoses in patients with ALS were dehydration and malnutrition (574 patients, 36%), pneumonia (507 patients, 32%), and respiratory failure (398 patients, 25%). Only 38% of patients with ALS were discharged to home without home health care compared with 73% of patients with non-ALS. Fifteen percent of patients with ALS died in the hospital compared with 3% of non-ALS patients. The average length of hospital stay and charges were greater for patients with ALS than for non-ALS patients (8.4 days and $19,810 for ALS patients and 5.4 days and $11,924 for non-ALS patients). Mortality was significantly associated with emergency room admission (versus nonemergency admission; OR = 1.60), increasing age (per year; OR = 1.03), respiratory failure (OR = 3.37), and pneumonia (OR = 2.02) (p < 0.01 for all comparisons). CONCLUSIONS: Patients with ALS have lengthy and costly hospital admissions, a high in-hospital mortality rate, and few routine discharges. Recognition of the issues that precipitate hospitalization may allow development of preventive strategies.

Three-dimensional CT-guided bronchoscopy with a real-time electromagnetic position sensor: a comparison of two image registration methods.

STUDY OBJECTIVES: To compare two different image registration methods for accurately displaying the position of a flexible bronchoscope on a previously acquired three-dimensional CT scan during bronchoscopy. SETTING: Bronchoscopy suite of a university hospital. PATIENTS: Fifteen adult patients scheduled for nonemergent bronchoscopy. METHODS: A miniature electromagnetic position sensor was placed at the tip of a flexible bronchoscope. Previously acquired three-dimensional CT scans were registered with the patient in the bronchoscopy suite. Registration method 1 used multiple skin fiducial markers. Registration method 2 used the inner surface of the trachea itself for registration. Method 1 was objectively assessed by measuring the error distance between the real skin marker position and the computer display position. Methods 1 and 2 were subjectively assessed by the bronchoscopist correlating visual bronchoscopic anatomic location with the computer display position on the CT image. RESULTS: The error distance (+/- SD) from known points for registration method 1 was 5.6 +/- 2.7 mm. Objective error distances were not measured for method 2 because no accurate placement of the bronchoscope sensor could be correlated with CT position. Subjectively, method 2 was judged more accurate than method 1 when compared with the fiberoptic view of the airways through the bronchoscope. Additionally, method 2 had the advantage of not requiring placement of fiducial markers before the CT scan. Respiratory motion contributed an error of 3.6 +/- 2.6 mm, which was partially compensated for by a second tracking sensor placed on the patient's chest. CONCLUSION: Image registration method 2 of surface fitting the trachea rather than method 1 of fiducial markers was subjectively judged to be superior for registering the position of a flexible bronchoscope during bronchoscopy. Method 2 was also more practical inasmuch as no special CT scanning technique was required before bronchoscopy.

Increased alpha2-adrenergic constriction of isolated arterioles in diffuse scleroderma.

OBJECTIVE: Vasospasm and ischemic organ injury are important in the pathogenesis of systemic sclerosis (SSc; scleroderma). The present study was performed to determine whether SSc arterioles have an intrinsic disturbance in vasoconstrictor activity. METHODS: Skin biopsy samples were obtained from the upper arm of 11 patients with diffuse SSc (clinically uninvolved skin) and 8 age- and sex-matched control subjects. Dermal arterioles were dissected from the biopsy sample and mounted in a myograph for continuous monitoring of arteriolar diameter. The resting internal diameter of control and SSc arterioles was similar (mean +/- SEM 164+/-15 micro and 166+/-18micro, respectively). RESULTS: Dermal arterioles displayed no spontaneous constrictor activity in the absence of stimulation. Vasoconstriction in response to KCI, a receptor-independent activator of smooth muscle, or to phenylephrine, a selective alpha1-adrenergic receptor (alpha1-AR) agonist, was similar in control and SSc arterioles. However, constrictor responses to UK 14,304, a selective alpha2-AR agonist, were increased in SSc compared with control arterioles (maximal constriction responses of 25+/-5% and 67+/-4% [mean +/- SEM] in control and SSc arterioles, respectively; P = 0.000014). Mechanical denudation of the endothelium did not alter reactivity to alpha2-AR activation, indicating that the enhanced constriction in SSc was not mediated by changes in endothelial dilator activity. Indeed, in arterioles constricted with phenylephrine, the endothelial stimuli acetylcholine or bradykinin evoked endothelium-dependent relaxation that was similar in control and SSc arterioles. CONCLUSIONS: Vascular smooth muscle in SSc arterioles displayed a selective increase in alpha2-AR reactivity. The endothelial dilator function appeared normal. Altered activity of smooth muscle alpha2-ARs may contribute to the vasospastic activity that is a prominent feature of the SSc disease process.

Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients.

OBJECTIVE: To assess the safety and potential efficacy of a mechanical ventilation strategy designed to reduce stretch-induced lung injury in acute respiratory distress syndrome. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: Eight intensive care units in four teaching hospitals. PATIENTS: Fifty-two patients with acute respiratory distress syndrome. INTERVENTIONS: Traditional tidal volume patients: tidal volume 10-12 mL/kg ideal body weight, reduced if inspiratory plateau pressure was > 55 cm H2O (7.3 kPa). Small tidal volume patients: tidal volume 5-8 mL/kg ideal body weight, to keep plateau pressure < 30 cm H2O (4.0 kPa). MEASUREMENTS AND MAIN RESULTS: Mean tidal volumes during the first 5 days in traditional and small tidal volume patients were 10.2 and 7.3 mL/kg, respectively (p < .001), with mean plateau pressure = 30.6 and 24.9 cm H2O (3.3 kPa), respectively (p < .001). There were no significant differences in requirements for positive end-expiratory pressure or FIO2, fluid intakes/outputs, requirements for vasopressors, sedatives, or neuromuscular blocking agents, percentage of patients that achieved unassisted breathing, ventilator days, or mortality. CONCLUSIONS: The reduced tidal volume strategy used in this study was safe. Failure to observe beneficial effects of small tidal volume ventilation treatment in important clinical outcome variables may have occurred because a) the sample size was too small to discern small treatment effects; b) the differences in tidal volumes and plateau pressures were modest; or c) reduced tidal volume ventilation is not beneficial.

Induction of heme oxygenase-1 with hemoglobin depresses vasoreactivity in rat aorta.

Septic shock induced by lipopolysaccharide (LPS) produces systemic hypotension and decreased responsiveness to vasoconstrictors. Recently, intravenous injection of hemoglobin (HGB) into rats was found to be protective from a subsequent lethal dose of LPS and was correlated with induction of the enzyme heme oxygenase-1 (HO-1). To determine whether the HGB modulated the vasomotor tone of systemic arteries, we evaluated the effect of in vivo treatment with HGB and LPS on vasoconstrictor responses to phenylephrine (PE) in the isolated rat aorta. Rats (n = 4, for each group) were injected intravenously with rat HGB (200 mg/kg i.v.) or normal saline control (CON) 16 h before sacrifice, and/or LPS (20 mg/kg) or CON 4 h before sacrifice. The descending aorta was dissected into rings and suspended in a modified Krebs solution where vasoconstrictor responses were determined to KCl (60 mM) and PE (10(-8) to 10(-5) M). LPS, but not HGB, inhibited the vasoconstrictor response to KCl. LPS, HGB, and HGB+LPS inhibited the maximal vasoconstrictor response to PE (PEmax). Induction of HO-1 RNA in the aorta by HGB and by LPS was demonstrated by Northern blot analysis. To determine if induction of HO-1 was related to the effect of LPS or HGB on vascular reactivity, vessels were treated with the HO-1 inhibitor, SnPP9 (30 microM). PEmax in SnPP9+HGB vessels was not different from control, whereas SnPP9+LPS vessels had a marked decrease in PEmax. We conclude that induction of HO-1 does not protect the rat aorta from the vasodepressor effects of LPS in vitro. Our results demonstrate, however, that the induction of HO-1 causes vasodepression, possibly via increased production of carbon monoxide.

Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha.

Chronic hypoxia induces polycythemia, pulmonary hypertension, right ventricular hypertrophy, and weight loss. Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding proteins that mediate adaptive responses to hypoxia, including erythropoietin, vascular endothelial growth factor, and glycolytic enzymes. Expression of the HIF-1alpha subunit increases exponentially as O2 concentration is decreased. Hif1a-/- mouse embryos with complete deficiency of HIF-1alpha due to homozygosity for a null allele at the Hif1a locus die at midgestation, with multiple cardiovascular malformations and mesenchymal cell death. Hif1a+/- heterozygotes develop normally and are indistinguishable from Hif1a+/+ wild-type littermates when maintained under normoxic conditions. In this study, the physiological responses of Hif1a+/- and Hif1a+/+ mice exposed to 10% O2 for one to six weeks were analyzed. Hif1a+/- mice demonstrated significantly delayed development of polycythemia, right ventricular hypertrophy, pulmonary hypertension, and pulmonary vascular remodeling and significantly greater weight loss compared with wild-type littermates. These results indicate that partial HIF-1alpha deficiency has significant effects on multiple systemic responses to chronic hypoxia.

The higher risk of bleeding in lung transplant recipients from bronchoscopy is independent of traditional bleeding risks: results of a prospective cohort study.

STUDY OBJECTIVE: To determine whether recipients of lung transplants have a higher risk of bleeding from fiberoptic bronchoscopy (FOB) than other patients who undergo the procedure. DESIGN: Prospective cohort study. SETTING: Bronchoscopy services of Johns Hopkins Hospital, a tertiary referral center and Johns Hopkins Bayview Medical Center, a community hospital. PATIENTS: All adult patients (18 years) who underwent FOB between July 1, 1996 and June 30, 1997 by the full-time pulmonary medicine staff were included. A total of 720 procedures were performed, including 38 in lung transplant recipients. MEASUREMENTS: Bleeding was assessed by reviewing physician reports of bloody drainage after the procedure and whether the procedure was terminated early for bleeding. Patient reports of hemoptysis were assessed using questionnaires administered pre- and post-FOB. Predictor variables included patient demographics, bleeding parameters (platelets, prothrombin time, and activated partial thromboplastin time), immunosuppressive medications, aspirin use, use of transbronchial biopsy, and the time length of the procedure. RESULTS: Lung transplant recipients were significantly more likely to have used aspirin prior to FOB (18.4 vs 7.2%, p < 0.05) and to undergo transbronchial biopsy (64.9 vs 26.8%, p < 0.001). Lung transplant patients were more likely to have new or worsened hemoptysis (53.8 vs 24.6%, p < 0.001), to have > 25 mL of blood loss (44.5 vs 17.5%, p < 0.001) and to have the procedure terminated early for bleeding (5.4 vs 1.0%, p < 0.05). In multivariate analysis, predictors of new or worsened hemoptysis included lung transplant, longer procedure time, and older patient age. Independent predictors of greater blood loss included lung transplant, performance of transbronchial biopsy, longer procedure time, and older patient age. CONCLUSIONS: Lung transplant recipients are at higher risk of bleeding from bronchoscopy than are other patients. This propensity to bleed is independent of coagulation parameters, platelet count, immunosuppressive medication use, aspirin use, or performance of transbronchial biopsy. The higher risk of bleeding should be considered when assessing the risks and benefits of bronchoscopy in lung transplant recipients.

Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1 in the lung.

Hypoxia-inducible factor (HIF)-1 is a basic helix-loop-helix transcription factor that transactivates genes encoding proteins that participate in homeostatic responses to hypoxia. Several of these downstream gene products, such as erythropoietin, vascular endothelial growth factor, heme oxygenase-1, and inducible nitric oxide synthase, may contribute to the pathogenesis of pulmonary hypertension. Previous studies demonstrated increased HIF-1 mRNA levels in rats and mice subjected to hypoxia. In this study, we have demonstrated spatial, temporal, and O2-dependent expression of HIF-1 protein. Immunoblot analysis revealed hypoxic induction of HIF-1 in all cultured pulmonary cell types assayed, including those derived from pulmonary arterial endothelium and smooth muscle, bronchial epithelium, alveolar macrophages, alveolar epithelium, and microvascular endothelium. In contrast to all other cell types, pulmonary arterial smooth muscle cells expressed HIF-1 under nonhypoxic conditions. Immunohistochemistry and immunoblot analysis of ferret lungs demonstrated pulmonary expression of HIF-1 in vivo. HIF-1 protein expression was induced maximally when lungs were ventilated with 0 or 1% O2 for 4 h. On reoxygenation, HIF-1 was rapidly degraded, with a half-life of <1 min. These findings demonstrate that HIF-1 expression is tightly coupled to O2 concentration in vivo and are consistent with the involvement of HIF-1 in the physiological and pathophysiological responses to hypoxia in the lung.

Superoxide and endothelium-dependent constriction to flow in porcine small pulmonary arteries.

1. The aim of this study was to determine the response of porcine small pulmonary arteries to intralumenal flow and to identify the cellular mechanisms and potential mediators involved in the response. 2. Porcine small pulmonary arteries were isolated from a branch of the main intrapulmonary artery of the lower lung lobe and studied in a perfusion myograph system that allowed independent control of transmural pressure and intralumenal flow. At a transmural pressure of 20 mmHg, the baseline internal diameter (BID) of the arteries was 251.2+/-16.1 microm (n=16). 3. Under quiescent conditions or during constriction with U46619 to approximately 60% of BID, intralumenal flow caused reversible constriction in arteries with endothelium (in the presence of U46619, flow decreased diameter from 60.0+/-2.5% to 49.5+/-3.0% BID at 10 microl min(-1), n=16, P<0.05) but no change in diameter of arteries without endothelium. 4. In the presence of superoxide dismutase (SOD, 150 u ml(-1)), the response to flow was converted from constriction to vasodilatation (in presence of U46619 and SOD, flow increased diameter from 54.2+/-3.4% to 76.7+/-4.5% BID at 10 microl min(-1), n=10, P<0.05). Inhibition of NO synthase with L-NAME (3 x 10(-5) M) abolished the flow-induced vasodilatation occurring in the presence of SOD and the flow-induced constriction occurring in the absence of SOD. In arteries with endothelium, L-NAME (3 x 10(-5) M) caused significant vasoconstriction, whereas SOD did not alter vasomotor tone. 5. Acetylcholine (10(-8) to 10(-6) M) caused endothelium-dependent relaxation of small pulmonary arteries that was not significantly affected by SOD (150 u ml(-1)) but was inhibited by L-NAME (3 x 10(-5) M). 6. These results suggest that in small, porcine, isolated pulmonary arteries, intralumenal flow increases the production of NO but this is obscured by the generation of superoxide which causes vasoconstriction.

In vivo expression of mRNAs encoding hypoxia-inducible factor 1.

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor that regulates genes whose products play key roles in maintaining O2 homeostasis. We have previously demonstrated that HIF-1 mRNA, protein, and DNA-binding activity are induced when mammalian tissue culture cells are subjected to hypoxia. In this paper, we report our analysis of HIF-1 mRNA expression in vivo. We demonstrate expression of HIF-1 alpha and HIF-1 beta (ARNT) mRNA in all human, rat, and mouse organs assayed and show for the first time that HIF-1 mRNA expression was induced in brain, kidney, and lung when rats or mice were exposed to reduced ambient O2 concentrations for 30 to 60 min. The ubiquitous in vivo expression of HIF-1 alpha and HIF-1 beta (ARNT) mRNA is consistent with the proposed role of HIF-1 in coordinating adaptive transcriptional responses to hypoxia.

Mechanisms of hypoxic vasodilation in ferret pulmonary arteries.

To investigate the mechanism of hypoxic pulmonary vasodilation we measured isometric tension in rings from ferret third- to fifth-generation intrapulmonary arteries mounted in organ baths (37 degrees C, 28% O2-5% CO2). After precontraction with phenylephrine (PE), hypoxia caused a brief transient vasoconstriction followed by marked vasodilation. Endothelial denudation did not affect the steady-state response. In vessels without endothelium, inhibition of cyclooxygenase and nitric oxide synthase had no effect on the response to hypoxia. Inhibition of ATP-dependent K+ channels (KATP) with glibenclamide, linogliride, or tolbutamide had no effect on normoxic tone before PE or the vasoconstrictor response to PE but inhibited hypoxic vasodilation. Inhibition of Ca(2+)-activated K+ (KCa) channels with charybdotoxin potentiated the vasoconstrictor response to PE but had no effect on hypoxic vasodilation. The nonspecific K(+)-channel inhibitor tetraethyl-ammonium (TEA) potentiated the response to PE and inhibited hypoxic vasodilation. Glibenclamide plus TEA inhibited hypoxic vasodilation more than either agent alone, suggesting that TEA inhibited the KATP-channel independent vasodilation. These results suggest that in isolated ferret pulmonary arteries hypoxia causes vasodilation partially by activating smooth muscle KATP channels. Activation of a TEA-sensitive channel that is not a KATP or KCa channel may also contribute to hypoxic vasodilation.

Effects of insulin, glucose analogues, and pyruvate on vascular responses to anoxia in isolated ferret lungs.

In isolated ferret lungs, the vasopressor response to anoxia is characterized by an intense initial vasoconstriction, followed by marked vasodilation. This hypoxic pulmonary vasodilation (HPVD) is inhibited by perfusate glucose concentration > or = 15 mM. To determine whether this inhibition of HPVD was mediated by an effect of glucose transport or a product of glucose metabolism beyond pyruvate, we studied the effects of 5 mM glucose + insulin, transportable but nonmetabolizable analogues of glucose, and pyruvate on the pulmonary vascular response to anoxia. Isolated ferret lungs were ventilated with 28% O2 at constant flow. Perfusate glucose concentration was allowed to fall spontaneously. Thirty-minute anoxic exposures were performed at 60, 120, and 180 min of perfusion. Before the third anoxic exposure 15 mM glucose, 15 mM sucrose, 5 mM glucose (with 10 mM sucrose) + 10 mU/ml insulin, 15 mM 3-O-methylglucose (3-O-MG), or 15 mM alpha-methylglucose (alpha-MG) was added to the perfusate and vasomotor responses recorded. In another series of experiments, 15 mM pyruvate was added to the preparation at the beginning of perfusion. Peak vasoconstrictor responses were not different among groups. HPVD was greater in sucrose, insulin, 3-O-MG, alpha-MG, and pyruvate lungs than in high glucose lungs. These results suggest that glucose transport or a product of glucose metabolism beyond pyruvate was not responsible for inhibiting HPVD. We speculate that hyperglycemia inhibits HPVD by increasing production of ATP from the glycolytic pathway and that this ATP inhibits ATP-dependent K+ channels.

ATP-dependent K+ channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs.

In normo- and hypoglycemic ferret lungs, the pulmonary vascular response to severe hypoxia (PiO2 less than or equal to 10 mmHg) is characterized by an initial intense vasoconstriction followed by marked vasodilation, whereas in hyperglycemic lungs, vasodilation is minimal, causing vasoconstriction to be sustained. In contrast, the response to moderate hypoxia is characterized by a slowly developing sustained vasoconstriction which is unaffected by glucose concentration. To determine the role of ATP-dependent K+ (KATP) channels in these responses, we examined the effects of cromakalim, which opens KATP channels, and glibenclamide, which closes them. During steady-state vasoconstriction induced in isolated ferret lungs by moderate hypoxia, cromakalim caused dose-dependent vasodilation (EC50 = 7 x 10(-7) M) which was reversed by glibenclamide (IC50 = 8 x 10(-7) M), indicating that KATP channels were present and capable of modulating vascular tone. During severe hypoxia in hypoglycemic lungs [( glucose] less than 1 mM), glibenclamide markedly inhibited the secondary vasodilation. Raising perfusate glucose concentration to 14 +/- 0.4 mM had the same effect. As a result, initial vasoconstrictor responses were well sustained. However, neither glibenclamide nor hyperglycemia affected vasoconstrictor responses to moderate hypoxia or KCl, indicating that effects during severe hypoxia were not due to nonspecific potentiation of vasoconstriction. These findings suggest that in the ferret lung (a) severe hypoxia decreased ATP concentration and thereby opened KATP channels, resulting in increased K+ efflux, hyperpolarization, vasodilation, and reversal of the initial vasoconstrictor response; and (b) hyperglycemia prevented this sequence of events.

Effects of glucose on hypoxic vasoconstriction in isolated ferret lungs.

To characterize the effects of glucose on the pulmonary vascular response to anoxia and hypoxia, isolated ferret lungs were ventilated with 28% O2 and 5% CO2 and perfused at constant flow (100 ml.kg-1.min-1). Perfusate glucose concentrations were allowed to fall spontaneously to less than 1 mM (low glucose) or were controlled at 5-6 mM (normal glucose) or 12-17 mM (high glucose). At 60, 120, and 180 min of perfusion, the inspired O2 tension (PIO2) was reduced to 0, 10, or 30 Torr for 30 min, and vasomotor responses were quantified by continuous measurement of pulmonary arterial pressure. At PIO2 of 0 Torr, the response consisted of an early phase of transient intense vasoconstriction and a late phase of sustained slight vasoconstriction. High glucose markedly potentiated the magnitude of late-phase vasoconstriction with each successive anoxic exposure. This effect was not reproduced in normal glucose lungs and was not caused by a change in perfusate osmolarity, an action on blood cells, or an altered ability of pulmonary vascular smooth muscle to contract. At PIO2 of 10 Torr, high glucose not only potentiated late-phase vasoconstriction but also slowed the onset of early-phase vasoconstriction. At PIO2 of 30 Torr, high glucose had no effect on vasomotor responses, which were characterized by a slowly developing sustained vasoconstriction. Our results suggest that the vascular response of isolated ferret lungs to severe hypoxia consisted of separate early and late phases of vasoconstriction. This biphasic response may have resulted from two distinct vasoconstrictor mechanisms or from modulation of a single vasoconstrictor mechanism by a secondary vasodilator influence.(ABSTRACT TRUNCATED AT 250 WORDS)

Prone position reverses gravitational distribution of perfusion in dog lungs with oleic acid-induced injury.

Although oxygenation improves in patients with the adult respiratory distress syndrome and in animals with oleic acid- (OA) induced acute lung injury when they are turned from the supine to the prone position, the mechanism(s) by which this improvement occurs is not known. Several groups have speculated that this improvement results from preferential edema accumulation in the dorsal lung regions and redistribution of perfusion away from these regions when the patients are turned to the prone position. We used radiolabeled microspheres to measure the regional distribution of perfusion (Qr) to the dorsal, mid, and ventral lungs of eight dogs in vivo in the supine and prone positions, before and after inducing acute lung injury with OA, and correlated the Qr observed after injury with the degree of regional extravascular lung water (EVLWr). Before OA, Qr increased along the gravitational gradient when the animals were supine but was more uniformly distributed when they were prone. After OA, Qr again followed a gravitational gradient when the animals were supine but was preferentially distributed to the nondependent regions when they were prone. EVLWr was similar in all regions, regardless of whether OA was injected when the animals were supine or prone. The gravitational Qr gradient is markedly reduced in the prone position, both before and after lung injury. The prone position-induced improvement in oxygenation is not the result of redistribution of Qr away from areas in which edema preferentially develops.

Left lower lobe ventilation is reduced in patients with cardiomegaly in the supine but not the prone position.

To determine the effect of the heart on regional ventilation, Krypton-81m (81mKr) tomographic (SPECT) ventilation scans were recorded in seven patients with cardiomegaly and four normal subjects in the supine and prone positions. All patients had a cardiothoracic ratio of greater than 0.50 and clear lung fields radiographically. Using standard gamma camera tomographic reconstruction techniques, images of transaxial slices were obtained during a 360 degree rotation around the thorax of the subject breathing the radioactive gas 81mKr. The transaxial images, acquired over 10 min were aligned in each posture at the level of the cardiac apex, mid-heart, and aortic arch and were matched in relation to a radioactive marker on the chest wall and to anatomic landmarks. A horizontal line (gravity independent and parallel to the couch) was drawn on the transaxial section through the dorsal regions of the right and left lung. Counts per resolution element (12 to 15 mm) were plotted along this line and the ratios of the peak values in right and left lung compared. These ratios represent differences in regional ventilation per unit lung volume. In controls the mean left-to-right (L/R) peak count ratio varied from 0.91 to 1.00 at the three levels (range: 0.76 to 1.04); there were no significant differences between supine and prone. In patients with cardiomegaly the mean (+/- SEM) L/R peak count ratio at cardiac apex, mid-heart, and aortic arch was 0.46 (+/- 0.08), 0.55 (+/- 0.07), and 0.89 (+/- 0.08) when supine and 1.04 (+/- 0.07), 1.05 (+/- 0.05), and 1.08 (+/- 0.07) when prone, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)