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Effects of acute nifedipine on functional liver plasma flow in normal subjects and cirrhotic patients
156
EFFECTS
P Aseni,
L Vizzotto,
C Tommasini Milan,
Degna.
of v a r i o u s
The purpose
of this study
that occur
antitumoral
solution
of M i t o m y c i n
devided
C (0.5 mg/Kg) of saline
18, 24, 48 hrs,
in osmium
and cut into one m i c r o n of h e p a t o c y t e s
fraction
of hepatocytes, the two groups showed
a significant to the control interfer w i t h
rats;
(nuclei
regeneration
are not w e l l known.
Niguarda
by a m o r p h o q u a n t i t a t i v e
into two groups:
i.p.
thick
30 min.
Hospital,
before
and c y t o p l a s m
2/3 hepatectomy,
50 control
liver r e g e n e r a t i o n progressed
of h e p a t o c y t e
only
In c o n c l u s i o n
evaluated
w e r e considered: bed,
and nuclei.
time points.
and nuclei
considered
there was as c o m p a r e d
w e r e o b s e r v e d at the
in our study M i t o m y c i n
in the early phase
surface
C t r e a t e d group
cytoplasm
the volume
Comparison
at the d i f f e r e n t
in the M i t o m y c i n
rats re-
liver was r e m o v e d
s p e c i m e n was fixed
device
and sinusoidal
in any of the p a r a m e t e r s
the two groups.
The liver
of cells
for each p a r a m e t e r
fraction
The r e m n a n t
parameters
separately),
and n u m b e r
C. One h u n d r e d
a 0 . 4 % saline
A semicomputerized
The f o l l o w i n g
size d i s t r i b u t i o n
no d i f f e r e n c e s
the s u c c e s s i o n
50 rats r e c e i v e d
and 2/3 hepatectomy.
slices.
methods.
of the volume
method
liver of rats treated w i t h M i t o m y c i n
has been p e r f o r m e d
between
liver r e g e n e r a t i o n
157
on h e p a t i c
that 12 hrs after h e p a t e c t o m y
decrease
other time points
VF Ferrario, II",
7, 14, 21 days after the operation.
by s t e r e o l o g i c a l
fraction
The results
M Frangi,
"Pizzamiglio
solution
4, 8, 12,
between
agents
in the r e g e n e r a t i n g
the same amount
liver s t r u c t u r e
CA Beati,
IN THE RAT.
of S u r g e r y
is to c h a r a c t e r i z e
male W i s t a r rats w e r e r a n d o m l y ceived
F Romani,
Department
C ON LIVER R E G E N E R A T I O N
Italy.
The effects of events
OF M I T O M Y C I N
(at the 12th h) w h i l e
C showed
to
thereafter
unaffectedly.
EFFECTS OF ACUTE NIFEDIPINE ON ~ C T I O N A L LIVER PLASMA FLOW IN NORMAL SD'BJECTS AND CIRRHOTIC
PATIENTS P. Avagnina, P.E. Aurucci, L. Fasulo, P. Caccamo, A. Cavanna~, M. Fracchia, G. Molino Dipartimento di Biomediciua, Universit~ deEli Studi di Torino and *~ Casa di Cura San Camillo, Torino, Italy. Recently it has been shown that liver blood flow significantly increases after acute administration of nifedipine (N) in normal subjects (Br J Clin Pharmacol 1984;17:83-85). Whether such an effect can be achieved in cirrho tics in un~mown. The present study investigates the effects of acute N (20 mg sublinsual ) on liver perfusion in i0 normal volunteers and 20 cirrhotics (I0 mild cases and 10 severe). All subjects were normotensive. The functio hal liver plasma flow (FLPF) was estimated by measuring the hepatic clearance of sorbitol (DiE Dis Science 1987 in press) before, 30 and 60 rain after drug administration. 2 FLPF (ml/min/m) normal subjects
30 min
60 min
544.9 + 67.9
639.3 + 107.2~
663.0 + 125.7~
mild cirrhosis
339.2 + 96.2
378.5 + 121.2~
388.2 + 126.0 °
severe cirrhosis
250.9 + 92.3
237.7 +_ 88.6 °
229.2 +
basal
83.6~
paired t test vs basal ~=p
Acute N significantly improves FLPF in normal subjects and mild cirrhosis, while significantly reducing it in se vere cirrhosis. Since no difference in the lowering of mean blood pressure was found in the three Eroups,
these
discrepances cannot be attributed to a systemic effect of N. As previously suEgested for verapemil (J Hepatol 1986;3:49-58), the increase of FLPF in normal subjects and mild cirrhosis could be explained by the opening of sinusoids not previously perfused. This should not occur in advanced cirrhosis, where all available sinusoids are basally recruited. In these patients the reduction of liver perfusion might be related to a further increase of intrahepatic shunting due to N. The different response observed in mild and decompensated cirrhosis may be employed in evaluating the prognosis of cirrhotic patients.
$84
EFFECTS
P Aseni,
L Vizzotto,
C Tommasini Milan,
Degna.
of v a r i o u s
The purpose
of this study
that occur
antitumoral
solution
of M i t o m y c i n
devided
C (0.5 mg/Kg) of saline
18, 24, 48 hrs,
in osmium
and cut into one m i c r o n of h e p a t o c y t e s
fraction
of hepatocytes, the two groups showed
a significant to the control interfer w i t h
rats;
(nuclei
regeneration
are not w e l l known.
Niguarda
by a m o r p h o q u a n t i t a t i v e
into two groups:
i.p.
thick
30 min.
Hospital,
before
and c y t o p l a s m
2/3 hepatectomy,
50 control
liver r e g e n e r a t i o n progressed
of h e p a t o c y t e
only
In c o n c l u s i o n
evaluated
w e r e considered: bed,
and nuclei.
time points.
and nuclei
considered
there was as c o m p a r e d
w e r e o b s e r v e d at the
in our study M i t o m y c i n
in the early phase
surface
C t r e a t e d group
cytoplasm
the volume
Comparison
at the d i f f e r e n t
in the M i t o m y c i n
rats re-
liver was r e m o v e d
s p e c i m e n was fixed
device
and sinusoidal
in any of the p a r a m e t e r s
the two groups.
The liver
of cells
for each p a r a m e t e r
fraction
The r e m n a n t
parameters
separately),
and n u m b e r
C. One h u n d r e d
a 0 . 4 % saline
A semicomputerized
The f o l l o w i n g
size d i s t r i b u t i o n
no d i f f e r e n c e s
the s u c c e s s i o n
50 rats r e c e i v e d
and 2/3 hepatectomy.
slices.
methods.
of the volume
method
liver of rats treated w i t h M i t o m y c i n
has been p e r f o r m e d
between
liver r e g e n e r a t i o n
157
on h e p a t i c
that 12 hrs after h e p a t e c t o m y
decrease
other time points
VF Ferrario, II",
7, 14, 21 days after the operation.
by s t e r e o l o g i c a l
fraction
The results
M Frangi,
"Pizzamiglio
solution
4, 8, 12,
between
agents
in the r e g e n e r a t i n g
the same amount
liver s t r u c t u r e
CA Beati,
IN THE RAT.
of S u r g e r y
is to c h a r a c t e r i z e
male W i s t a r rats w e r e r a n d o m l y ceived
F Romani,
Department
C ON LIVER R E G E N E R A T I O N
Italy.
The effects of events
OF M I T O M Y C I N
(at the 12th h) w h i l e
C showed
to
thereafter
unaffectedly.
EFFECTS OF ACUTE NIFEDIPINE ON ~ C T I O N A L LIVER PLASMA FLOW IN NORMAL SD'BJECTS AND CIRRHOTIC
PATIENTS P. Avagnina, P.E. Aurucci, L. Fasulo, P. Caccamo, A. Cavanna~, M. Fracchia, G. Molino Dipartimento di Biomediciua, Universit~ deEli Studi di Torino and *~ Casa di Cura San Camillo, Torino, Italy. Recently it has been shown that liver blood flow significantly increases after acute administration of nifedipine (N) in normal subjects (Br J Clin Pharmacol 1984;17:83-85). Whether such an effect can be achieved in cirrho tics in un~mown. The present study investigates the effects of acute N (20 mg sublinsual ) on liver perfusion in i0 normal volunteers and 20 cirrhotics (I0 mild cases and 10 severe). All subjects were normotensive. The functio hal liver plasma flow (FLPF) was estimated by measuring the hepatic clearance of sorbitol (DiE Dis Science 1987 in press) before, 30 and 60 rain after drug administration. 2 FLPF (ml/min/m) normal subjects
30 min
60 min
544.9 + 67.9
639.3 + 107.2~
663.0 + 125.7~
mild cirrhosis
339.2 + 96.2
378.5 + 121.2~
388.2 + 126.0 °
severe cirrhosis
250.9 + 92.3
237.7 +_ 88.6 °
229.2 +
basal
83.6~
paired t test vs basal ~=p
Acute N significantly improves FLPF in normal subjects and mild cirrhosis, while significantly reducing it in se vere cirrhosis. Since no difference in the lowering of mean blood pressure was found in the three Eroups,
these
discrepances cannot be attributed to a systemic effect of N. As previously suEgested for verapemil (J Hepatol 1986;3:49-58), the increase of FLPF in normal subjects and mild cirrhosis could be explained by the opening of sinusoids not previously perfused. This should not occur in advanced cirrhosis, where all available sinusoids are basally recruited. In these patients the reduction of liver perfusion might be related to a further increase of intrahepatic shunting due to N. The different response observed in mild and decompensated cirrhosis may be employed in evaluating the prognosis of cirrhotic patients.
$84