DTIC ADA238225: Variation of TFAA in Liver Cells After an Inhalation of Halothane

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225
AD-A238
VARIATION 01' TFAA IN LIVER CELLS AFTER AN INHALATION
OF HALOTHANE
K. Arai, H. Fujii, M. Morio, M. Nakao, M. Shiraishi,
H. Kinoshita, M. Takahashi and N. Sato
Dept. of Anethesia, Medical School, Hiroshima University
Masui to Sosei 1989, vol 25 (suppl 22), pp 81-3
DTIG
ISJULO 81991U
Translated by;
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VARIATION OF TFAA IN LIVER CELLS AFTER AN INHALATION
OF HALOTHANE
K. Arai, H. Fujii, M. Morio, M. Nakao, M. Shiraishi,
H. Kinoshita, M. Takahashi and N. Sato
Dept. of Anc.thesia, Medical School, Hiroshima University
Trifluoroacetic acid (TFAA) which is the final metabolic
substance of halothane, is discharged in urine. Its peak is
around 10 hours after inhalation of halothane. The mechanism of
this retardation of discharge may be attributed to the circula-
tion of TFAA in intestines and the liver or to metabolism of
halothane deposited on fatty tissues after inhalation of haloO
thane. We previously discussed the possibility of the former.
In the present work, we performed the experiment which examined
the possibility of the latter.
Experimental method
ICR mice (weight about 30 g) which were seven weeks old,
inhaled 1% halothane in the air for two hours. After two hours
of inhalation, we dissected them at 0, 1, 3, 10, 24, 48 and 96
hours and recovered their livers and collected blood samples
from their hearts. The livers were cleaned by biological saline
solution and homogenated by distilled water. The resulting
homogenated liver was ultra filtered to yielding liver cells.
We determined TFAA concentration liver cells and blood by ion-
chromatography. Further, halothane concentration in blood was
determined by the equilibrium method using gas chromatography.
The value of TFAA was expressed by mean ±SD, its inspection was
done by the student t-test. When the risk rate is less than 5%,
we regarded it as significant. We also determined the distribu- 0
tion volume and half value period of halothane concentration n
applying a two compartment model.
IDiltribution/
Availability Codes
Avail and/ol'
Dist Speoial
Results
We did not detect any TFAA in liver cells and blood samples
of mice which did not inhale halothane. In Figure 2, we show
variations of TFAA concentration in liver cells. The TFAA con-
centration increased up to five hours after the end of inhala-
tion. The significance was 5% right after and three hours after
the end of the inhalation and 1% after five hours at the end of
the inhalation, respectively. Figure 3 shows variations of TFAA
conc ntrati.L,,, in blood. The TFAA concentration became maximum
five hours after the end of inhalation. It displays a very
similar trend to that in liver cells. Figure 4 depicts variation
of halothane concentration in blood. The halothane concentration
was highest at the end of inhalation and we did not detect any
trace of halothane 10 hours after the end of inhalation. The
distribution volume of organs whose blood stream flow is very
large like the liver was about 90.7 times larger than those
organs whose blood flow is slow like fatty tissues. Further,
the half value period was 10.7 min. and 99.5 min. for high speed
blood flow organs and low speed blood flow organs, respectively.
Figure 1. Experimental method 7j (j30g)
rI :
1--ICR mouse: 7 weeks old (wt.
about 30g); 2--inhalation of 1% YMTIZ20%R
halothane in the air for 2 hrs;
3--0.1, 3.5, 10, 24, 48, 96 hrs
after the end of inhalation; J 0,|,3,5.024,48,96
4--liver taken out; 5--liver
cleaned; 6--homogenate was pre-=l ffj t il
pared; 7--ultra filtration;
8--blood sample taken; 9--TFAA
measurement; 10--halothane C t, E --
7
measurement I5
2
TFA in liver cell (mean±So) (UMoI/L) TFA in blood (mean±SD)
1000 . . 2000
Zo oo00
Ip<
3 *.,! I .0
" co -~--O___-_-- ..I. . ...-I.---.-- .. . 10oi I...!.-.,i: I
400 - _.- - _m , ! J r ; i aI] ___
C00 0
0 20 40 60 00 100 0 20 40 60 8U '100
time in hours time in hours
Figure 2 Figure 3
Discussion
i mol Halothane in Blood
The increase in TFAA after the
I =7243.89t 0.42t inhalation of halothane is due to
C=712.4e
3
TI/ a=-10.7min the production of TFAA in the liver.
2 =99.Smnn
2TI/2,
2 . V/V~2=9.7 The retardation of discharge in the
10 V N =90.7
1 2
101 urine is attributed to the fact
that halothane deposited on fatty
0 1 2 3 4 5 6 tissues is metabolized continuously
time in hours
Figure 4 tafter the inhalation of halothane.
Since the TFAA level in the blood
varies very similarly with that in the liver, TFAA may be consi-
dered to easily pass through liver cell membranes, The distri-
bution volume and half value period for the organs whose blood
flow speed is fast were about 90.7 times larger and about 1/9
smaller than those for the organs whose blood flow speed is slow.
References
[11 ,* Okita, et al.: Effect of inhaled halothane concentration
on the discharge of trifluoroacetic acid (TFAA). Masui to
Sosei, 19: 39-42, 1983
[2] K. Sakai, et al.: Effect of fatty tissues at Monmyaku area
on metabolic deqradation of halothane. M.sui tu &osci,
22: 65-69, 1986
[3] H. Kinoshita, et al.: Effect of trifluoroacetic acid (TFAA)
Masui to Sosei, 24: 53-55, 1988
3