Pulmonary Clearance Of 99mTc-DTPA Research Articles

Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid in healthy individuals.

To evaluate the effects of positive expiratory pressure (PEP) on pulmonary epithelial membrane permeability in healthy subjects. We evaluated a cohort of 30 healthy subjects (15 males and 15 females) with a mean age of 28.3 ± 5.4 years, a mean FEV1/FVC ratio of 0.89 ± 0.14, and a mean FEV1 of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) radioaerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels-10 cmH2O (n = 10), 15 cmH2O (n = 10), and 20 cmH2O (n = 10). The 99mTc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. The pulmonary clearance of 99mTc-DTPA was significantly shorter when PEP was applied-at 10 cmH2O (p = 0.044), 15 cmH2O (p = 0.044), and 20 cmH2O (p = 0.004)-in comparison with that observed during spontaneous breathing. Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects. Avaliar os efeitos da pressão expiratória positiva (PEP) na permeabilidade da membrana epitelial pulmonar em indivíduos saudáveis. Foi avaliada uma coorte de 30 indivíduos saudáveis (15 homens e 15 mulheres), com média de idade de 28,3 ± 5,4 anos, média da relação VEF1/CVF de 0,89 ± 0,14 e média de VEF1 de 98,5 ± 13,1% do previsto. Os indivíduos foram submetidos a cintilografia pulmonar por inalação de radioaerossol de ácido dietilenotriaminopentacético marcado com tecnécio-99m (99mTc-DTPA em inglês) em dois estágios: durante respiração espontânea e durante respiração com uma máscara de PEP de 10 cmH2O (n = 10), 15 cmH2O (n = 10) ou 20 cmH2O (n = 10). O 99mTc-DTPA foi nebulizado por 3 min, e sua depuração foi registrada por cintilografia por um período de 30 min durante respiração espontânea e por um período de 30 min durante a respiração com uma máscara de PEP. A depuração pulmonar do 99mTc-DTPA foi significativamente menor quando PEP foi aplicada a 10 cmH2O (p = 0,044), 15 cmH2O (p = 0,044) e 20 cmH2O (p = 0,004), em comparação com a observada durante a respiração espontânea. Nossos achados indicam que o uso de PEP nos níveis testados pode induzir um aumento na permeabilidade da membrana epitelial pulmonar e no volume pulmonar em indivíduos saudáveis.

Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid in healthy individuals

ABSTRACTObjective: To evaluate the effects of positive expiratory pressure (PEP) on pulmonary epithelial membrane permeability in healthy subjects. Methods: We evaluated a cohort of 30 healthy subjects (15 males and 15 females) with a mean age of 28.3 ± 5.4 years, a mean FEV1/FVC ratio of 0.89 ± 0.14, and a mean FEV1 of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) radioaerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels-10 cmH2O (n = 10), 15 cmH2O (n = 10), and 20 cmH2O (n = 10). The 99mTc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. Results: The pulmonary clearance of 99mTc-DTPA was significantly shorter when PEP was applied-at 10 cmH2O (p = 0.044), 15 cmH2O (p = 0.044), and 20 cmH2O (p = 0.004)-in comparison with that observed during spontaneous breathing. Conclusions: Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects.

The effect of airway deposition on the assessment of lung injury by 99mTc-DTPA clearance--lung injury in interstitial lung diseases assessed by using the duplicated 99mTc-DTPA aerosol inhalation method

The 99mTc-DTPA aerosol inhalation method permits detection of pulmonary epithelial damage. We investigated one of several problems, airway deposition of inhaled aerosol, on the assessment of pulmonary epithelial permeability in healthy nonsmokers and patients with interstitial lung diseases. We used the rate constant of pulmonary 99mTc-DTPA clearance curve, k, as a parameter of the epithelial permeability. The alveolar-peripheral airway deposition of aerosol was estimated by the duplicated inhalation method, which we newly developed. The mean k in patients with interstitial lung diseases (2.52 +/- 0.72%/min, n = 8; p less than 0.01) was significantly greater than that in healthy nonsmokers (0.92 +/- 0.20%/min, n = 4). The alveolar-peripheral airway deposition was similar in both healthy nonsmokers and interstitial lung diseases (73.5 +/- 7.8% and 75.5 +/- 9.2%, respectively). The mean k corrected for alveolar-peripheral airway deposition (corrected k; kc) was higher in patients with interstitial lung diseases (4.08 +/- 1.63%/min; p less than 0.01) as compared with healthy nonsmokers (1.36 +/- 0.47%/min). The mean k was significantly greater than the mean kc in both groups (p less than 0.01, p less than 0.01). However, there was a significant correlation between the k and kc obtained among the subjects (r = 0.951; p less than 0.01). We, therefore, conclude that correction for alveolar-peripheral airway deposition was not necessary to distinguish the patients with interstitial lung diseases from the healthy nonsmokers using 99mTc-DTPA aerosol inhalation method although the correction was significant in the individual subjects.

Lung clearance of 99mTc-DTPA in systemic lupus erythematosus

The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99mTc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99mTc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99mTc-DTPA is increased in SLE patients with active disease.

Alveolar epithelial integrity in athletes with exercise-induced hypoxemia.

The effect of incremental exercise to exhaustion on the change in pulmonary clearance rate (k) of aerosolized (99m)Tc-labeled diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) and the relationship between k and arterial PO(2) (Pa(O(2))) during heavy work were investigated. Ten male cyclists (age = 25 +/- 2 yr, height = 180.9 +/- 4.0 cm, mass = 80.1 +/- 9.5 kg, maximal O(2) uptake = 5. 25 +/- 0.35 l/min, mean +/- SD) completed a pulmonary clearance test shortly (39 +/- 8 min) after a maximal O(2) uptake test. Resting pulmonary clearance was completed >/=24 h before or after the exercise test. Arterial blood was sampled at rest and at 1-min intervals during exercise. Minimum Pa(O(2)) values and maximum alveolar-arterial PO(2) difference ranged from 73 to 92 Torr and from 30 to 55 Torr, respectively. No significant difference between resting k and postexercise k for the total lung (0.55 +/- 0.20 vs. 0. 57 +/- 0.17 %/min, P > 0.05) was observed. Pearson product-moment correlation indicated no significant linear relationship between change in k for the total lung and minimum Pa(O(2)) (r = -0.26, P > 0.05). These results indicate that, averaged over subjects, pulmonary clearance of (99m)Tc-DTPA after incremental maximal exercise to exhaustion in highly trained male cyclists is unchanged, although the sampling time may have eliminated a transient effect. Lack of a linear relationship between k and minimum Pa(O(2)) during exercise suggests that exercise-induced hypoxemia occurs despite maintenance of alveolar epithelial integrity.

Pulmonary clearance of 99mTc-DTPA in experimental surfactant dysfunction treated with surfactant instillation.

Breakdown of the alveolo-capillary barrier is a characteristic feature of respiratory distress syndrome. Restoration of alveolo-capillary barrier function may be an important aspect of surfactant replacement therapy. We examined the effect of surfactant instillation on alveolo-capillary barrier function in an experimental model of surfactant dysfunction by measuring pulmonary clearance of 99mTc-DTPA. Nineteen rabbits were tracheotomized and mechanically ventilated. Surfactant dysfunction was induced by administration of a synthetic detergent in aerosol form. Detergent was given to 13 rabbits; seven rabbits were then treated with instillation of natural surfactant, whereas six rabbits received saline. Six rabbits were used as untreated controls. An aerosol of 99mTc-DTPA was administered to all animals and the pulmonary clearance was measured with a gamma camera. 99mTc-DTPA cleared from the lungs with a half-life of 71 +/- 22 min in the control animals, 21.4 +/- 7.4 min in the surfactant-treated animals and 5.8 +/- 1.5 min in the saline-treated animals. The difference in half-life between groups was highly significant (P < 0.001). There was no change in arterial oxygenation or compliance in controls or in animals treated with saline. In animals treated with surfactant, a small transient reduction in arterial oxygen tension and a more long-standing reduction in compliance were observed. Surfactant treatment thus significantly attenuated the effect of detergent treatment but did not restore alveolo-capillary transfer of 99mTc-DTPA to normal.

Effect of detergent combined with large tidal volume ventilation on alveolocapillary permeability.

The combined effect of large tidal volume ventilation (LTVV) and detergent-induced surfactant dysfunction on the clearance kinetics of technetium-99m-labelled diethylene triamine pentaacetate was investigated. Four groups of rabbits (n = 6 in each) were studied: (1) controls, (2) detergent, (3) LTVV, and (4) detergent + LTVV. Clearance was measured for 3 h and the kinetics was analysed by fitting mono- and biexponential equations to the clearance curve and was expressed as a half-life (T 1/2). Pulmonary clearance of 99mTc-DTPA was monoexponential in control animals (T 1/2 = 194 min) and in animals ventilated with LTVV (T 1/2 = 43 min, P < 0.01 compared with controls). In contrast, clearance was biexponential after detergent administration with or without LTVV. T 1/2 values of the fast and slow compartments were 5.4 and 80 min, respectively, with the fast fraction comprising 81% of the radioactivity after detergent alone. When detergent was combined with LTVV, clearance was bicompartmental as with detergent alone, with the same size of the fast fraction. However, clearance from each of the slow (P < 0.01) and fast compartments (P < 0.05) increased significantly. Clearance from the slow compartment was thus similar to T 1/2 during LTVV alone. Large tidal volume ventilation induced a faster than normal clearance of a single compartment, whereas detergent induced kinetics that was distinctly bicompartmental. The mechanisms increasing permeability of the alveolocapillary barrier after detergent and during LTVV seem different and may be additive.

Evaluation of lung function after intratracheal perfluorocarbon administration in healthy animals.

To investigate the effects of partial liquid ventilation (i.e., mechanical ventilation in combination with intratracheal administration of perfluorocarbon) on lung function, with particular attention to the integrity of the alveolocapillary membrane in healthy adult animals. Prospective, randomized, controlled study. Laboratory at the Department of Experimental Anesthesiology, Erasmus University Rotterdam. Ten adult male New Zealand rabbits. Five rabbits were intratracheally treated with 12 mL/kg of perfluorocarbon while conventional mechanical ventilation (volume-controlled, tidal volume of 12 mL/kg, respiratory rate of 30 breaths/min, inspiration/expiration ratio of 1:2, positive end-expiratory pressure of 2 cm H2O, and an FIO2 of 1.0) was applied for 3 hrs. To assess the permeability of the alveolocapillary membrane, pulmonary clearance of inhaled technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) measurements were performed at 3 hrs and compared with data from the control group (n = 5) treated with mechanical ventilation only, using the same ventilatory parameters. Pulmonary gas exchange and lung mechanical parameters were measured in both groups at 30-min intervals. Mean values for PaO2 in the perfluorocarbon group, although at adequate levels, were less than those values of the control group during the 3-hr study period (370 +/- 44 vs. 503 +/- 44 torr at 3 hrs [49.3 +/- 5.9 vs. 67.1 +/- 5.9 kPa]). Peak and mean airway pressures were higher in the perfluorocarbon group (ranging from 1.9 to 3.4 cm H2O and 0.7 to 1.3 cm H2O, respectively) compared with the control group, while end-inspiratory airway pressure was similar in both groups. The half-life of 99mTc-DTPA was 83.7 +/- 24.5 mins in the control group, which was significantly longer (p < .01) than in the perfluorocarbon group (49.8 +/- 6.1 mins). These findings suggest that partial liquid ventilation with perfluorocarbons lowers pulmonary gas exchange in healthy animals, and the increased pulmonary clearance of 99mTc-DTPA after 3 hrs of this type of ventilatory support may reflect minimal reversible changes in the lung surfactant system.

Biexponential pulmonary clearance of 99mTc-DTPA induced by detergent aerosol.

We measured the pulmonary clearance of technetium-99m-labeled diethylenetriamine pentaacetatic acid (99mTc-DTPA) for 3 h after perturbation of the surfactant system by administration of the detergent dioctyl sodium sulfosuccinate in aerosol. Forty-two rabbits were anesthetized with pentobarbital sodium. Tracheostomies were performed, and the rabbits were mechanically ventilated. Increasing concentrations of detergent (0.125-2%) or vehicle were given for 5 min, and clearance measurements were performed immediately or 60 min after detergent administration. No animals developed respiratory distress. After vehicle, the clearance was monoexponential with a half-life of 153 min. Detergent induced a biexponential clearance with a rapidly clearing additional pool of radioactivity with a half-life of 5-15 min. The relative amount of radioactivity clearing rapidly increased with detergent concentration. The detergent effect was partly reversible. We conclude that detergent induces a biexponential clearance of 99mTc-DTPA by accelerating the transfer of tracer across the alveolocapillary barrier in a proportion of lung units in a dose-related manner.

Sequential changes in pulmonary epithelial permeability after birth in term and preterm rabbits.

We assessed sequential changes in the permeability properties of the pulmonary epithelium in spontaneously breathing, newborn term (30 days of gestation) and preterm (28 days) rabbit pups, using the rate of pulmonary clearance of 99mTc-DTPA (MW = 492) as an index of permeability. In term rabbits, clearance was faster at 1 h of age than at hourly timepoints thereafter (p < 0.05). In preterm rabbits, clearance rates measured from 1 to 5 h after birth were not quite significantly different (p = 0.0519) although the trend to slower clearance with increasing time after birth was significant. When term and preterm rabbits were compared, clearance was similar at 1 h after birth but was faster at both 2 and 3 h in the preterm rabbits (p < 0.05). Pulmonary epithelial permeability appears to be increased in the immediate postnatal period and the duration of increased permeability is longer in preterm rabbits. Because lung water content at birth is greater in the preterm rabbits, we speculate that the permeability changes may be associated with clearance of fetal lung liquid.

Bleomycin lung toxicity detected by technetium-99m diethylene triamine penta-acetic acid aerosol scintigraphy.

In this study we investigated bleomycin-induced pulmonary toxicity in patients with germ-cell tumour by means of technetium-99m diethylene triamine penta-acetic acid aerosol scintigraphy. Twenty untreated patients who had no clinical or radiological evidence of pulmonary disease received four courses of etoposide, cisplatin and bleomycin chemotherapy. Aerosol lung scintigraphy and pulmonary function tests were performed in all patients before bleomycin treatment and after administration of 180 and 360 mg bleomycin. On the basis of the scintigrams the percentage decline in activity per minute (Kep) was evaluated, which represented an accurate parameter of lung membrane permeability. Pretreatment Kep values (0.891 +/- 0.286) were significantly lower than those obtained following 180 and 360 mg bleomycin treatment (1.176 +/- 0.336 and 1.389 +/- 0.477, respectively; P < 0.0005). The Kep values obtained with 180 and 360 mg bleomycin treatments were also significantly different (P < 0.005). In contrast, no significant change was observed in the results of pulmonary function tests. Our results demonstrate that evaluation of the pulmonary clearance of 99mTc-DTPA represents a useful means of monitoring the functional status of the lung epithelial membrane during bleomycin treatment. Further prospective studies are needed to assess the relationship between increase in permeability and development of lung toxicity in order to decide which patients should discontinue bleomycin therapy.

Detection of radiation-induced lung injury by 99mTc-DTPA aerosol inhalation method

We prospectively monitored pulmonary 99mTc-DTPA (diethylene triamine penta acetate) clearance in patients who received chest radiation therapy, in order to determine whether this method allows us to predict the development of radiation pneumonitis. The rate constant of pulmonary 99mTc-DTPA clearance (k; %/min) was used to assess pulmonary epithelial damage. Fifteen nonsmoking patients who underwent radiation therapy were studied. The subjects included 4 patients who had already developed radiation pneumonitis at the time of study, and 11 in whom we prospectively observed 99mTc-DTPA clearance serially during the course of chest radiation therapy. In the 4 patients with pre-existing radiation pneumonitis, the mean k value obtained from the area with infiltration on the chest X-ray was significantly greater than that from the opposite lung (p < 0.02). In the prospective study, 3 out of 11 patients developed radiation pneumonitis. The mean k of the irradiated lung field in the 8 patients who did not develop radiation pneumonitis was unchanged. The mean k value obtained in the 3 patients who did develop radiation pneumonitis increased just before the onset, and further increased when the disease manifested clinically. We conclude that pulmonary 99mTc-DTPA clearance may be useful for predicting the development of radiation pneumonitis.

Influence of chest background on pulmonary 99mTc-DTPA clearance in interstitial lung disease.

We examined the effect of chest extracellular 99mTc-diethylenetriamine pentaacetate (DTPA) as a background in the measurement of pulmonary 99mTc-DTPA clearance in patients with interstitial lung disease (ILD). Eight healthy nonsmokers (HN) and eight patients with ILD were studied. We monitored changes in gamma counts after the inhalation of 99mTc-DTPA aerosol by using a gamma camera placed over the anterior chest. The rate constant of pulmonary 99mTc-DTPA clearance (k; %/min) was assessed by calculating the slope of the decrease in the gamma counts. The chest background, estimated by 99mTc-DTPA intravenous injection, was subtracted from the original data to obtain the corrected DTPA clearance (kc; %/min). In patients with ILD, k was significantly greater [2.19 +/- 1.03 (SD) %/min; n = 8] compared with HN (0.86 +/- 0.17%/min; n = 8; P < 0.01). In patients with ILD, kc was also greater (2.80 +/- 1.15%/min; n = 8; P < 0.01) compared with HN (1.20 +/- 0.12%/min; n = 8). There was no difference in percent underestimation of k between the two groups (29.1 +/- 8.8% for HN, 22.5 +/- 7.9% for patients with ILD). There was a significant correlation between k and kc among all subjects (r = 0.987, P < 0.01). We conclude that background causes significant underestimation of pulmonary 99mTc-DTPA clearance.

Integrity of the alveolar-capillary barrier and alveolar surfactant system in smokers.

The permeability of the alveolar-capillary barrier to technetium-99m labelled diethylenetriamine pentaacetate (99mTc DTPA) is known to be greatly increased in smokers, but the underlying mechanism is poorly understood. Abnormal permeability of the alveolar epithelium as well as impaired surfactant function has been suggested. The purpose of this study was to examine transudation of urea and albumin into the alveoli and alveolar surfactant function in smokers and non-smokers and to relate these variables to the rate of alveolar-capillary transfer of 99mTc DTPA. Standardised bronchoalveolar lavage was performed and the yield of urea and albumin measured in the lavage fluid. The integrity of the alveolar surfactant system was assessed by measurement of the surface activity and of the yield of phospholipids in alveolar lavage fluid. The mean decay constant for the pulmonary clearance of 99mTc DTPA was 0.028/min in the smokers and 0.009/min in the non-smokers. The recovery of albumin and urea in alveolar lavage fluid was very similar in the two groups. The surface activity of alveolar lavage fluid was lower in smokers than in non-smokers (minimum surface tension 37.9 versus 28.6 mN/m) and the yield of phospholipids was reduced (2.08 versus 3.86 mg). The rate constant for the pulmonary clearance of 99mTc DTPA correlated with the yield of phospholipids at bronchoalveolar lavage. The study shows that increased alveolar-capillary transfer of 99mTc DTPA in smokers is not accompanied by increased transudation of small or large molecules into the alveoli. The findings support the hypothesis that increased clearance of 99mTc DTPA in smokers is related to surfactant dysfunction.

Pulmonary clearance of 99mTc‐DTPA during halothane anaesthesia

We studied the integrity of the alveolo-capillary barrier during different forms of anaesthesia by measuring the pulmonary clearance of inhaled 99mTc-DTPA. We studied four groups of rabbits. Groups I and II were anaesthetized with nembuthal only and the fractional concentration of inspired oxygen (F1O2) was 0.30 and 1.00, respectively. Groups III and IV were anaesthetized with 1% halothane and F1O2 was 0.30 and 0.99, respectively. 99mTc-DTPA was administered as a fine aerosol and the clearance of the tracer from the lungs was subsequently measured with a gamma camera. The mean half-life of the tracer in the lungs in Groups I-IV was 60, 58, 59 and 26 min, respectively. The rapid pulmonary clearance of 99mTc-DTPA in Group IV indicates that halothane in combination with high oxygen concentration increases the permeability of the alveolo-capillary barrier. This may be due to effects on the pulmonary surfactant system and/or the alveolar epithelium.

Pulmonary clearance of 99mTc-DTPA: influence of background activity.

We examined the effect of intravascular and tissue accumulation of tracer when measuring pulmonary clearance of sodium pertechnetate-labeled diethylenetriamine pentaacetate (99mTc-DTPA). Pigs were intubated with endobronchial tubes, permitting deposition of an aerosol of 99mTc-DTPA only into the left lung. Scintillation detectors recorded radioactivity separately from one thigh and from the lung and chest wall on the left and right side. 99mTc-DTPA was given intravenously after 30 min, so that the chest counts from the left lung could be corrected for background activity in either the right lung or the thigh. The uncorrected clearance half time (t1/2) mean +/- SE from the left chest was 118.5 +/- 14.4 min. When corrected for background activity in the right chest, the t1/2 was 82.1 +/- 10.5 min, and when corrected for background activity in the thigh, the t1/2 was 80.9 +/- 10.6 min. There was no significant difference between t1/2 corrected by the measurements from the right chest or the thigh, and in four of five animals the corrected t1/2 by either method was significantly different from the uncorrected t1/2 (P less than 0.05). There was no correlation between the uncorrected t1/2 and the magnitude of the required correction. We conclude that correction for intravascular and tissue accumulation of tracer is an important refinement of the technique and can easily be accomplished by measuring accumulation of tracer in the thigh.

Effect of increased surface tension and assisted ventilation on 99mTc-DTPA clearance

Experiments were performed to determine the effects of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) on the clearance of technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from lungs with altered surface tension properties. A submicronic aerosol of 99mTc-DTPA was insufflated into the lungs of anesthetized, tracheotomized rabbits before and 1 h after the administration of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Rabbits were ventilated by one of four methods: 1) spontaneous breathing; 2) CMV at 12 cmH2O mean airway pressure (MAP); 3) HFO at 12 cmH2O MAP; 4) HFO at 16 cmH2O MAP. Administration of OT resulted in decreased arterial PO2 (PaO2), increased lung wet-to-dry weight ratios, and abnormal lung pressure-volume relationships, compatible with increased surface tension. 99mTc-DTPA clearance was accelerated after OT in all groups. The post-OT rate of clearance (k) was significantly faster (P less than 0.05) in the CMV at 12 cmH2O MAP [k = 7.57 +/- 0.71%/min (SE)] and HFO at 16 cmH2O MAP (k = 6.92 +/- 0.61%/min) groups than in the spontaneously breathing (k = 4.32 +/- 0.55%/min) and HFO at 12 cmH2O MAP (4.68 +/- 0.63%/min) groups. The clearance curves were biexponential in the former two groups. We conclude that pulmonary clearance of 99mTc-DTPA is accelerated in high surface tension pulmonary edema, and this effect is enhanced by both conventional ventilation and HFO at high mean airway pressure.

Pulmonary clearance of 99mTc-DTPA: a noninvasive assessment of epithelial integrity.

Nonstratified epithelium lines the respiratory tract from the trachea to distal lung units. An abnormality in the integrity of this critical barrier to the outside environment has been suggested as promoting or exacerbating a wide variety of clinical disorders ranging from asthma to acute lung injury syndromes. Recently the noninvasive measurement of the clearance rate of aerosolized and deposited99mtechnetium diethylenetriaminepentaacetate (99mTc-DTPA) has been used to assess pulmonary epithelial integrity. This paper discusses the merits and limitations of this technique, which is presently under extensive investigation in many research centers investigating pulmonary disease.

Measurement of pulmonary epithelial permeability with 99mTc-DTPA aerosol

The rate at which inhaled aerosol of 99mTc-diethylenetriamine pentaacetate (DTPA) leaves the lung by diffusion into the vascular space can be measured with a gamma camera or simple probe. In normal humans, 99mTc-DTPA clears from the lung with a half time of about 80 minutes. Many acute and chronic conditions that alter the integrity of the pulmonary epithelium cause an increased clearance rate. Thus cigarette smoking, alveolitis from a variety of causes, adult respiratory distress syndrome (ARDS), and hyaline membrane disease (HMD) in the infant have all been shown to be associated with rapid pulmonary clearance of 99mTc-DTPA. Rapid clearance is also promoted by increased lung volume and decreased surfactant activity. Although the mechanism of increased clearance in pathological states is not known, the 99mTc-DTPA lung-clearance technique has great potential clinically, particularly in patients at risk from ARDS and HMD and in the diagnosis and follow-up of alveolitis.

Pulmonary clearance of inhaled 99mTc-DTPA: effect of surfactant depletion in rabbits.

We examined the effect of surfactant depletion on the rate of pulmonary clearance of inhaled 99mTc-diethyl-triamino-penta-acetate (DTPA). 99mTc-DTPA was administered as a fine aerosol to four control animals and to four animals after wash-out of pulmonary surfactant. Care was taken to minimize structural damage to the lavaged lungs. Clearance of 99mTc-DTPA was measured over the right lung by external counting. The clearance rate was substantially increased in the lavaged animals compared to the control animals. We conclude that the pulmonary surfactant system is a rate-limiting factor for the absorption of inhaled 99mTc-DTPA. Measurement of the pulmonary clearance of 99mTc-DTPA may provide a new means for studying the pathogenetic role of the surfactant system in a variety of lung diseases.