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A research study investigating the regional lung clearance of Technetium-99m diethylenetriaminepentaacetic acid (DTPA) in seven nonsmoking volunteers during rest and exercise. The study reveals significant increases in apical lung clearance rates due to enhanced apical blood flow and permeability surface area product during exercise.
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tniaminepentaacetic acid ([99mTc]DTPA) has been used to assess the alveolobronchiolar permeability in
patients (1-5). Technetium-99m DTPA is a small hy
idly cleared by the lungs and, supposedly, crossing the alveolar capillary barrier through interepithelial junc tions (6). However, little is known about the variations
physiologic conditions which lead to changes of the distribution, perfusion, or ventilation within the lung
regional ventilation and perfusion of the lung which have been thoroughly studied (8, 9). Therefore, we studied the effect of a mild exercise performed in seated posture on the regional lung clearance of [99mTc]DTPA
Received Dec. 5, 1984; revision accepted Oct. 15, 1985. For reprints contact: Michel Meignan, MD, Départementde Me decine NuclCaire et de Biophysique, Centre Hospitalo-Universitaire Henri-Mondor, 51, avenue du MarCchal de Lattre de Tassigny Crc teil 94000, France.
Seven healthy nonsmoking volunteers, three men and four women, age ranging from 25 to 36 yr. were selected for the experimental procedure. An aerosol ofdroplets was generated from a 30 mCi (1.1 1 X lO9Bq) [99mTc]DTPA solution in 10 ml 9% sodium chloride using a glass nebulizer under 1.5 bar pressure and at a flow rate of 25.1 mint. The droplets were then dried by flowing through a fenestrated pipe surrounded by silicagel. The air stream containing the dry residue contin uously flowed through a broad-bore tube where the subject inhaled this dry aerosol through the inspiratory valve ofa face mask. The radioactivity from the tube and from the expira tory line was removed by means ofa low-resistance filter. The characteristics of the dry particles were measured with an electrical mobility analyzert as described (10). The particles had a count median diameter of 0.045 @,a geometric dcvi ation of I .7 resulting in a mass median diameter of 0.6 @. The subjects were submitted to the following procedure. They breathed the aerosol with a normal tidal volume for 5 mm. The expiratory gases were collected from the expiratory line during the inhalation. The subjects then sat on an ergo metric bicycle, their backs in front of a large field gamma cameras linked to a minicomputer1. A surgical strip placed under their shoulders prevented the subjects from moving. The lung field radioactivity data were framed at I mm inter vals during a resting and an exercising period; resting period
274 Meignan,Rosso,Leveauetal The Journal of Nuclear Medicine
Exercise Increases the Lung Clearance
of Inhaled Technetium-99m DTPA
Michel Meignan, Jean Rosso, Jean Leveau, AndréKatz, Luc Cinotti, Guy Madelaine,
Dêpartement de MédecineNuc/êaire et de Biophysique, Centre Hospitalo-Universitaire Henri -Mondor, Creteil; and Laboratoire de Physique et de Mêtro/ogie des aerosols, Institut de Protection et de Suireté Nucléaire,Cen, Fontenay Aux Roses France
The regional lung clearance of a depOSited aerosol of [99@Tc]diethylenetriaminepentaacetic acid
0.75% min1 s.d. at rest, n = 7, p <0.01). By contrastthe changesof the basal clearances
area product.
lasted 20 mm. As the twentieth frame was achieved, the exercise period started. Exercise was sustained for the next 7 mm at 50 W with a pedal speed of 60-70 cycles min@. The subjects had previously kept their shoulders carefully against the camera during pedaling for another experimental proce dure. The respiratory and heart rate were recorded immedi ately prior to and at the completion of exercise. One region of interest (ROl) was selected over each lung, on the first image of the resting phase, and subsequently divided at the level of the hilum by a horizontal line resulting in two other ROIs corresponding to upper and lower lung fields (later referred to as apex and base). These ROIs were applied to all the framed data of each study. Radioactivity was corrected for radionuclide decay and the data were sub mitted to a monoexponential regression analysis. An expo nential line of best fit was calculated for each ROI. The negative slope of this regression line was designated as the clearance rate “k―and was expressed in terms of percentage decrease of the radioactivity per mm (% min'). The clear ance rates of the right and left total lung fields, apices, and bases were computed on the data obtained during the 20-mm resting period. In order to make an adequate comparison with the data obtained during the 7-mm exercising period, the clearance rates were also computed on the first 7 mm of the resting period. However, to compute the clearance rates of apices and bases on these 7-mm intervals, the count rates from both apices or both bases were added for statistical reasons. Using this process, at the beginning of the resting period the initial count rate over the apical ROIs averaged 14,143 ± 6,567 per mm. The regression lines obtained corresponded closely at rest and at exercise to the data point: The correla tion coefficients (r) were always > 0.95 for the 20-mm clear ances and always >0.90 for the 7-mm clearances. No correc tion was done for radioactivity contained in pulmonary blood pool, or chest wall.
the exercise could be influenced by the mucociliary transport, two roughly rectangular ROl chosen to represent 10%of the area of each lung image and centered around the hilus were drawn. The integrated count rates did not increase in these
ing period. In contrast, a slight decrease was observed in both regions ( I,525 ±650 cpm compared with 1,380 ±820 for the right lung, n 7, N.S., 1,344 ±748 cpm compared with 880 ± 455 cpm for the left lung, n = 7, p <0.02). To assess the influence of the extrapulmonary thoracic background (stomach, renal, hepatosplenic activity) on the measurements of lower lung field activity, the count rate value in a rectangular ROI drawn between the lung bases and the kidneys was computed. This value did not change signifi cantly with time (768 ±41 2 cpm in the first minute compared with 965 ±552 cpm in the twenty-seventh mm). The mean count per pixel averaged 16.8 ±2.4% of the mean count pixel obtained in the basal ROI of the lung.
In three subjects (1, 5, 7) the regional ventilation per unit volume was measured at rest and after 7 mm of exercise at
(slmKr) For each experimental condition, minute ventilation was measured with a classic spirometer and a posterior view
of 300,000 counts was recorded during steady state inhalation ofthe gas delivered through a face mask. Inhalation was then discontinued by removal of the mask. One-second frames were recorded during the washout phase. Radioactivity curves were obtained from the apices and the bases of the lungs. A line was fitted to the initial uncorrected exponential section of the washout curve to give the clearance (including both physical decay and biological clearance). Ventilation per unit alveolar volume (V/V) was then calculated by substract ing the decay constant of stmKr (3.2 min@) as previously described (1 1). The apicobasal ratios of ventilation per unit volume were expressed at rest and at exercise. In order to test the influence of the duration of the acquisi tion on the [99mTc]DTpA clearance values, a control study was performed in five other nonsmoking subjects ranging in age from 27 to 40 yr. After the inhalation, the lung radioactiv ity was followed during 27 mm, at rest. The clearance rates were computed as previously described during the first 7 mm and between the twentieth to the twenty-seventh minutes of the study.
Comparisons among the clearances ofthe total lung field at rest and at exercise were performed using a two-factor analy sis of variance within each group. Comparisons among the clearances of apices and bases at rest and at exercise were performed between the experimental and the control group using a three-factor variance analysis with repeated measure ments (12) followed by a two-factor analysis. Student's paired t-test was used for other comparisons. Values were expressed as the mean ±s.d., p value 0.05 was accepted as indicating statistic significance.
tion was 460 ml ±259 and the deposition of the aerosol was homogeneous (Fig. I ). Their mean respiratory rate before @ exercise was 12.7 ±3 min. Their mean heart rate was 94 ± 10 min@ which can be explained by some initial anxiety before starting to pedal (Table I). The clearance rates of their total lung field measured at rest were not significantly differ ent whether computed in the first 7 mm (Table 2) or during the 20 mm ofthe resting period: 1.56 ±1.1 1% min@ for the right lung and 1.46 ±0.55% min@ for the left lung com pared with 1.45 ±0.87% min@ and 1.23 ±0.58% min1, respectively. The clearance rates computed during the entire resting period in each apex and base showed that the apical clear ances were significantly higher than the basal clearances I. ±0.95% mint compared with I .30 ±0.76% min@ (p <0.05, n 7) for the right lung and I .59 ±0.58% min@ compared with 1.1 I ±0.55% min1 (p <0.02, n 7) for the left lung (Fig. 2). No difference was found between the right and left lung by the variance analysis. At rest, the apical V/V computed with 8ImKr was lower than the basal V/V (0.7 ±0.2 min@ compared with 1.26 ± 0.2 min'). The distribution of V/V between the apex and basewas I: 1.6.
Volume 27 •Number 2 •February 1986 275
rateSubject Heart rate Respiratory (min1)no. Age (min1)
26Mean±s.d. 35 F 110 120 13
29±10p* 94±10 120±19 12± <0.01* <0.
exercise.t I Rest immediately before the II =Exercise.p II.following Value obtained comparing values obtained from Iand
significantlycomputed the values computed immediately and those field and remained constant, it does not
min1)Subject Basesno. Age Left lung Rightlung Apices
. I First 7 mm of resting period. t II = Exercise for experimental group and interval between twentieth and twenty-seventh mm of resting period for control group. t p Value obtained comparing values obtained from I and II.
Heart Rates and Respiratory Rates at Rest and Exercise
Experimental136M0.781.79232M1.202.53329F1.511.81426M2.513.58534F1.761.89625F1.053.05735F1.462.18Mean
0.69Pt<0.05Control827F0.850.67940F1.681.891029F0.761.101128M0.820.751234F0.940.94Mean ±s.d.1.46 ±0.562.4 ±
0.48ptN.S. ±s.d.1.01 ±0.381.07 ±
Volume 27 •Number 2 •February 1986 277
I
3-
-@ I (
1@@
••;-@@;@base apex base FIGURE 2
is significantly higher in apices than in bases (p < 0.05)
I
:
[99@'Tc]DTPAat rest and exercise in seven subjects. (0) Means; (1.) s.d. In apIces, mean clearance rate is signifi nential fit depends on the count nate in every ROl and, cantly different at exercise from mean at rest (p < 0.01)
regression analysis averaged 0.94 ±0.06.
causes a doubling of the apical clearance of the
from accumulation of radioactivity in chest wall or in
mechanism would have resulted in an hilar accumula
mm exercising period.
cisc on the alveolar distension must also be discussed.
sion (4). Experiments on normal subjects or animals
upright posture, which can be explained in terms of
At exercise we observed some redistribution of the
apical ventilation value ratio increased 50% more than
278 Meignan,Rosso,Leveauetal (^) The Journal of Nuclear Medicine
VA/Q in man at rest and with exercise measured with krypton-81m.J App! Physiol44(1):115—123, 1978
10. Bricard J, Perrin ML, Madelaine G: Aerosol size mea surement by electrical mobility and diffusion analysis.
Grant, 1980, pp 804-
human respiratory tract. JAerosolSci 8:25 1—267, 1977
World Congress ofNuclear Medicine andBiology, Vol. III, Raynaud C, ed. New York, Pergamon Press, 1982,
normal adults. Circ Res 37:379—389, 1975 I8. Rizk N, Luce J, Hoeffel J, et al: Site of deposition and
canine lungs. J App! Physio!: 56:723-729, 1984
ventilation-perfusion ratio in the lung, measured with radioactive CO2. J Appl Physiol 15:405-410, 1960
AnnRevResDis 127:299, 1983
280 Meignan,Rosso,Leveauetal (^) The Journal of Nuclear Medicine