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Solubility coefficients of 133Xe in water, saline, dog blood and organs
Solubility Coefficients of 133Xe in Water, Saline, Dog Blood and Organs* MERAL Department
of Nuclear
Medicine,
T. ERCAN
Hacettepe (Received
University
Medical
Center.
Ankara.
Turkey
20 April 1979)
Solubility coefficients of ‘33Xe in water, saline, dog blood and various dog organs were measured at 37’C. The self-absorption of ‘33Xe in different media and scatter of radioactivity were also determined. The specific gravities of organ samples were measured in water using pycnometers. The solubility coefficient of r3’Xe obtained in the present investigation was different in each organ.
Introduction RADIOISOTOPE clearance technique has been used quite frequently to determine organ blood flow since the introduction of the method by KETY.(‘*‘) However, it is necessary to accurately measure the solubility coefficients of the radioactive inert gases such as ‘33Xe or 85Kr in different tissues and blood before the organ blood flow studies are attempted. In the literature the solubility coefficients of ‘33Xe are reported only for a limited number of tissues and the values are not identical for the same tissue!3-12’ Therefore, we decided to remeasure these parameters including, this time, some other tissues’ solubility coefficients not previously reported in the literature.
Materials
and Methods
‘33Xe was purchased from the Radiochemical Centre, Amersham, England. Distilled water and saline were purchased from Haver Laboratories and used without further purification. Heparinized blood was taken from dogs. Plasma was separated by centrifugation. Samples with varying hematocrit values were prepared by mixing different amounts of plasma and red cells. They were haemolyzed by rapid freezing at -20°C and then thawing. Fresh samples of brain, liver, kidney, pancreas, spleen and fat tissues were obtained from dogs. These samples except fat were accurately weighed and homogenized with a predetermined volume of distilled water, first in a blender, then in a homogenizer (Potter S, B. Braun).
* This work was supported Turkish
Scientific
by grant No. TAG-322 and Technical Research Council.
of the
757
Samples of tissue fat were dissolved in a solution of I volume ether + 3 volumes ethanol to give solutions with varying fat concentrations. Mercuric chloride to a concentration of 0.05% was added to the samples of plasma, haemolyzed blood, tissue homogenates and fat solutions to prevent bacterial growth.” ” The prepared samples were placed in “Vacutainer” tubes and ‘33Xe was injected into the tubes and left in a water bath at 37 _t O.OYC for equilibration according to the methods described previously.‘7B’0’ The equipment used for radioactivity measurements was very similar to that described by VEALL and MALLETT”‘) and the measurements were made according to their methods, The self-absorption of ‘33Xe in different media and the scatter of radioactivity arising from outside the phase under measurement was determined as described previously. ‘*I The linear absorption coefficients (p) and correction factors (a) were calculated.“3’ The radioactivity count rates were corrected for background and self-absorption and the Ostwald solubility coefficients were expressed as the ratio between radioactivity in the liquid and gas phases. The solubility coefficients of ‘33Xe in various organs ‘were calculated from the measured solubilities in tissue homogenates using the following formula:
i
=
=T[&($+Vi)-i,v,]
T wT
Where AT = solubility & = solubility ogenates A, = solubility
coefficient of ’ 33Xe in tissues coefficient of ‘33Xe in homcoefficient
of ‘33Xe in water
Mcwl
758
T. Ercuu TABLE I. Linear
absorption coefficients (p) and correction factors for self-absorption (Mean + SD)
W, = weight of tissue sample VW= volume of water SGT = specific gravity of tissues
I vol. ether + 3 vol. ethanol
Water, saline and tissue homogenates
The specific gravity of tissue samples mined in water using pycnometers.
were deterp CI No. of observations
0.149 * 0.01 I 1.075 + 0.005 30
0.068 * 0.020 1.034 + 0.010 8
Results The values obtained for the absorption coefficients for ‘33Xe in water, saline and tissue homogenates were not significantly different from each other, so they were combined and the mean and standard deviation were calculated. The results for the linear absorption coefficients (p) together with the factors (a) used to correct the actual counting rates for selfabsorption are summarized in Table 1. Scatter for ‘33Xe was not detected in our setup. The specific gravities of organs and tissues are summarized in Table 2. These values were used in the calculations of the solubility of Xe in the respective organs. The solubility of 133Xe in dog blood is shown as a function of the hematocrit in Fig. 1. The solubility of L33Xe in erythrocytes was obtained from the extrapolated value (H = 100) in this graph. Figure 2 shows the solubility coefficients of ‘33Xe in solutions of fat as a function of percent fat (w/v) in ether (1) + ethanol (3) mixture. The solubility in fat was obtained from the extrapolated value at .Y = 100. The Ostwald solubility coefficients of ‘33Xe in water, saline, plasma, erythrocytes and various organs and tissues are summarized in Table 3. Discussion
TABLE 2. Specific
gravities of organs and tissues Specific gravity
Organ or tissue Liver Spleen Kidney Pancreas Brain Fat
TABLE
1.090 f 1.070 f 1.057 + 1.049 f 1.045 + 0.991 f
3. Solubility coefficients of lJ3Xe (Mean f SD x IO-‘) No. of observations
Medium Water (distilled) Saline Plasma
27 34 21
Red blood cells Brain Liver Kidney Pancreas Spleen Fat
28 I4 9 IO IO I2 20
The linear absorption coefficient (~0 of 133Xe in water, saline and tissue homogenates was 0.149
0
10
IO
30
‘0
*m.tawit
83.6 + 82.3 + 90.5 f 92.7* 191.9* 175.3 * 118.7 + 123.8 k 145.3 f 76.7 k 1953.X*
* Extrapolation value. t Total brain tissue.
00
00
70
00
at
00
(9. 1
FIG. I. Solubility coefficients of ‘j3Xe in blood as a function of haematocrit.
37 C
Solubility coefficients
100
00
0.006 0.003 0.005 0.008 0.002 0.005
100
6.1 4.0 4.0 5.4t 10.5 4.4 10.6 5.2
759
FIG. 2. Solubility coefficients of ‘j3Xe in fat solutions as a function of fat concentration.
k 0.011 and the correction factor was a = 1.075 + 0.05. These figures agree well with those reported by found p = 0.146 + 0.0031 and KITANI(*) who a = 1.074 f 0.0017 in water. Scatter for 133Xe was not observed in our measurements as was also reported by KITANI.@’ Our results for the solubility coefficients of ‘33Xe in water, saline, plasma and red blood cells are similar to those reported by LADEFOGED and ANDERSON”’ and KITANI@’ but different from those of CONN,@’ ISBISTER er al.") and VEALL and MALLETT.“” Kitani used a similar experimental setup and made the necessary corrections for self-absorption. However he did not measure the solubility coefficients of ‘33Xe in tissues. The solubility coefficients of ‘33Xe in tissues as measured in this study show variations from those reported in the literature, which are also different from each other. CONN~“) made his measurements at 21°C on dog tissues such as brain, liver, kidney and fat and the others’7.‘0.‘4) on human brain tissues only at 37°C. The values reported by Conn are higher than the corresponding results from the present study and from other investigators which can be attributed to the lower temperature at which the measurements were made. Conn’s setup for radioacitivity measurements and sample preparation technique were also different from the others. Xenon-133 has been widely used in the determination of blood flow in various organs by the tissue clearance method. But the solubility coefficients of 133Xe in those organs widely used in blood flow studies have not been determined under the same conditions of temperature, setup for radioactivity measurements and correction for self-absorption. In blood flow calculations a partition coefficient of 0.65470 between organ and blood, has been used,
which was derived from CONN’S~~) figures for organs such as kidney, liver, spleen and intestines.t’5.‘6*17’ However, in this study we obtained different solubility coefficients of 133Xe in each organ and as a result calculated partition coefficients (2) for organ/blood will be different from each other and will show variations depending on haemotocrit which should also be taken into consideration. Acknowlrd~ements-The author is grateful to Dr Muhlise Alvur of Medical and Surgical Research Center for providing the tissue samples used in this study.
References I. KETY S. S. Am. Hrurt J. 38, 32 1 (I 949). 2. KETY S. S. Pharmucol. RPC..3, I (I951 ). 3. ANDERSON A. M. and LADCFOGED J. J. Pharm. Sci. 54, 1684 (1965). 4. ANDERSEN A. M. and LADEFOCED J. J. C/in. Lab. Inwsr. 19, 72 (1967). 5. GILLESPIE F. G. Physics Med. Biol. 10, 561 (1965). 6. CONN H. L. J. rrppl. Physiol. 16, 1065 (1961). 7. ISBISTERW. N.. SCHOFIELD P. F. and TORRANCE H. B. Physics Med. Biol. 10, 243 (1965). 8. KITANI K. Stand. J. ckn. Lab. Intiest. 29, 167 (1972). 9. LADEF~GED J. and ANDERSEN A. M. Physics Med. Biol. 12, 353 (1967). IO. VEALL N. and MALLETT B. L. Physics Med. Biol. 10, 375 (1965).
II. YEH S. Y. and PETERSONR. E. J. crppl. Phpsiol. 20. 1041 (1965). 12. ERCAN M. T., BOR N. M., BEKDIK C. F. and ~NER G. PJliiyers Arch. 348, 51 (1974). 13. ROHRER R. H. In Principles of Nuclear Medicine (Edited by WAGNER H. N.), p. 114. Saunders, Philadelphia (1968). 14. O’BRIEN M. D. and VEALL N. Physics Med. Biol. 19,
472 (1974). 15. SANDBERG G. Acta physiol. stand. 84, 208 (1972). 16. SELKURTE. E. and WATHEN R. L. Gasrroenteroloyy 52, 387 (1967).
of Nuclear
Medicine,
T. ERCAN
Hacettepe (Received
University
Medical
Center.
Ankara.
Turkey
20 April 1979)
Solubility coefficients of ‘33Xe in water, saline, dog blood and various dog organs were measured at 37’C. The self-absorption of ‘33Xe in different media and scatter of radioactivity were also determined. The specific gravities of organ samples were measured in water using pycnometers. The solubility coefficient of r3’Xe obtained in the present investigation was different in each organ.
Introduction RADIOISOTOPE clearance technique has been used quite frequently to determine organ blood flow since the introduction of the method by KETY.(‘*‘) However, it is necessary to accurately measure the solubility coefficients of the radioactive inert gases such as ‘33Xe or 85Kr in different tissues and blood before the organ blood flow studies are attempted. In the literature the solubility coefficients of ‘33Xe are reported only for a limited number of tissues and the values are not identical for the same tissue!3-12’ Therefore, we decided to remeasure these parameters including, this time, some other tissues’ solubility coefficients not previously reported in the literature.
Materials
and Methods
‘33Xe was purchased from the Radiochemical Centre, Amersham, England. Distilled water and saline were purchased from Haver Laboratories and used without further purification. Heparinized blood was taken from dogs. Plasma was separated by centrifugation. Samples with varying hematocrit values were prepared by mixing different amounts of plasma and red cells. They were haemolyzed by rapid freezing at -20°C and then thawing. Fresh samples of brain, liver, kidney, pancreas, spleen and fat tissues were obtained from dogs. These samples except fat were accurately weighed and homogenized with a predetermined volume of distilled water, first in a blender, then in a homogenizer (Potter S, B. Braun).
* This work was supported Turkish
Scientific
by grant No. TAG-322 and Technical Research Council.
of the
757
Samples of tissue fat were dissolved in a solution of I volume ether + 3 volumes ethanol to give solutions with varying fat concentrations. Mercuric chloride to a concentration of 0.05% was added to the samples of plasma, haemolyzed blood, tissue homogenates and fat solutions to prevent bacterial growth.” ” The prepared samples were placed in “Vacutainer” tubes and ‘33Xe was injected into the tubes and left in a water bath at 37 _t O.OYC for equilibration according to the methods described previously.‘7B’0’ The equipment used for radioactivity measurements was very similar to that described by VEALL and MALLETT”‘) and the measurements were made according to their methods, The self-absorption of ‘33Xe in different media and the scatter of radioactivity arising from outside the phase under measurement was determined as described previously. ‘*I The linear absorption coefficients (p) and correction factors (a) were calculated.“3’ The radioactivity count rates were corrected for background and self-absorption and the Ostwald solubility coefficients were expressed as the ratio between radioactivity in the liquid and gas phases. The solubility coefficients of ‘33Xe in various organs ‘were calculated from the measured solubilities in tissue homogenates using the following formula:
i
=
=T[&($+Vi)-i,v,]
T wT
Where AT = solubility & = solubility ogenates A, = solubility
coefficient of ’ 33Xe in tissues coefficient of ‘33Xe in homcoefficient
of ‘33Xe in water
Mcwl
758
T. Ercuu TABLE I. Linear
absorption coefficients (p) and correction factors for self-absorption (Mean + SD)
W, = weight of tissue sample VW= volume of water SGT = specific gravity of tissues
I vol. ether + 3 vol. ethanol
Water, saline and tissue homogenates
The specific gravity of tissue samples mined in water using pycnometers.
were deterp CI No. of observations
0.149 * 0.01 I 1.075 + 0.005 30
0.068 * 0.020 1.034 + 0.010 8
Results The values obtained for the absorption coefficients for ‘33Xe in water, saline and tissue homogenates were not significantly different from each other, so they were combined and the mean and standard deviation were calculated. The results for the linear absorption coefficients (p) together with the factors (a) used to correct the actual counting rates for selfabsorption are summarized in Table 1. Scatter for ‘33Xe was not detected in our setup. The specific gravities of organs and tissues are summarized in Table 2. These values were used in the calculations of the solubility of Xe in the respective organs. The solubility of 133Xe in dog blood is shown as a function of the hematocrit in Fig. 1. The solubility of L33Xe in erythrocytes was obtained from the extrapolated value (H = 100) in this graph. Figure 2 shows the solubility coefficients of ‘33Xe in solutions of fat as a function of percent fat (w/v) in ether (1) + ethanol (3) mixture. The solubility in fat was obtained from the extrapolated value at .Y = 100. The Ostwald solubility coefficients of ‘33Xe in water, saline, plasma, erythrocytes and various organs and tissues are summarized in Table 3. Discussion
TABLE 2. Specific
gravities of organs and tissues Specific gravity
Organ or tissue Liver Spleen Kidney Pancreas Brain Fat
TABLE
1.090 f 1.070 f 1.057 + 1.049 f 1.045 + 0.991 f
3. Solubility coefficients of lJ3Xe (Mean f SD x IO-‘) No. of observations
Medium Water (distilled) Saline Plasma
27 34 21
Red blood cells Brain Liver Kidney Pancreas Spleen Fat
28 I4 9 IO IO I2 20
The linear absorption coefficient (~0 of 133Xe in water, saline and tissue homogenates was 0.149
0
10
IO
30
‘0
*m.tawit
83.6 + 82.3 + 90.5 f 92.7* 191.9* 175.3 * 118.7 + 123.8 k 145.3 f 76.7 k 1953.X*
* Extrapolation value. t Total brain tissue.
00
00
70
00
at
00
(9. 1
FIG. I. Solubility coefficients of ‘j3Xe in blood as a function of haematocrit.
37 C
Solubility coefficients
100
00
0.006 0.003 0.005 0.008 0.002 0.005
100
6.1 4.0 4.0 5.4t 10.5 4.4 10.6 5.2
759
FIG. 2. Solubility coefficients of ‘j3Xe in fat solutions as a function of fat concentration.
k 0.011 and the correction factor was a = 1.075 + 0.05. These figures agree well with those reported by found p = 0.146 + 0.0031 and KITANI(*) who a = 1.074 f 0.0017 in water. Scatter for 133Xe was not observed in our measurements as was also reported by KITANI.@’ Our results for the solubility coefficients of ‘33Xe in water, saline, plasma and red blood cells are similar to those reported by LADEFOGED and ANDERSON”’ and KITANI@’ but different from those of CONN,@’ ISBISTER er al.") and VEALL and MALLETT.“” Kitani used a similar experimental setup and made the necessary corrections for self-absorption. However he did not measure the solubility coefficients of ‘33Xe in tissues. The solubility coefficients of ‘33Xe in tissues as measured in this study show variations from those reported in the literature, which are also different from each other. CONN~“) made his measurements at 21°C on dog tissues such as brain, liver, kidney and fat and the others’7.‘0.‘4) on human brain tissues only at 37°C. The values reported by Conn are higher than the corresponding results from the present study and from other investigators which can be attributed to the lower temperature at which the measurements were made. Conn’s setup for radioacitivity measurements and sample preparation technique were also different from the others. Xenon-133 has been widely used in the determination of blood flow in various organs by the tissue clearance method. But the solubility coefficients of 133Xe in those organs widely used in blood flow studies have not been determined under the same conditions of temperature, setup for radioactivity measurements and correction for self-absorption. In blood flow calculations a partition coefficient of 0.65470 between organ and blood, has been used,
which was derived from CONN’S~~) figures for organs such as kidney, liver, spleen and intestines.t’5.‘6*17’ However, in this study we obtained different solubility coefficients of 133Xe in each organ and as a result calculated partition coefficients (2) for organ/blood will be different from each other and will show variations depending on haemotocrit which should also be taken into consideration. Acknowlrd~ements-The author is grateful to Dr Muhlise Alvur of Medical and Surgical Research Center for providing the tissue samples used in this study.
References I. KETY S. S. Am. Hrurt J. 38, 32 1 (I 949). 2. KETY S. S. Pharmucol. RPC..3, I (I951 ). 3. ANDERSON A. M. and LADCFOGED J. J. Pharm. Sci. 54, 1684 (1965). 4. ANDERSEN A. M. and LADEFOCED J. J. C/in. Lab. Inwsr. 19, 72 (1967). 5. GILLESPIE F. G. Physics Med. Biol. 10, 561 (1965). 6. CONN H. L. J. rrppl. Physiol. 16, 1065 (1961). 7. ISBISTERW. N.. SCHOFIELD P. F. and TORRANCE H. B. Physics Med. Biol. 10, 243 (1965). 8. KITANI K. Stand. J. ckn. Lab. Intiest. 29, 167 (1972). 9. LADEF~GED J. and ANDERSEN A. M. Physics Med. Biol. 12, 353 (1967). IO. VEALL N. and MALLETT B. L. Physics Med. Biol. 10, 375 (1965).
II. YEH S. Y. and PETERSONR. E. J. crppl. Phpsiol. 20. 1041 (1965). 12. ERCAN M. T., BOR N. M., BEKDIK C. F. and ~NER G. PJliiyers Arch. 348, 51 (1974). 13. ROHRER R. H. In Principles of Nuclear Medicine (Edited by WAGNER H. N.), p. 114. Saunders, Philadelphia (1968). 14. O’BRIEN M. D. and VEALL N. Physics Med. Biol. 19,
472 (1974). 15. SANDBERG G. Acta physiol. stand. 84, 208 (1972). 16. SELKURTE. E. and WATHEN R. L. Gasrroenteroloyy 52, 387 (1967).