O U R N A L
Y a ra M a rc o n d e s M a c h a d o C a s tig lia , J o s é R e in a ld o C e rq u e ira B ra z , P e d ro T h a d e u G a lv ã o V ia n n a , L in o L e m o n ic a , L u iz A n to n io V a n e
E f f e c t o f h ig h - d o s e f e n ta n y l o n r e n a l f u n c tio n in d o g s
Departamento
de Anestesiologia
da Faculdade de Medicina de Botucatu - UNESP - São Paulo, Brazil
O u r o b je ctive w a s to d e te rm in e th e e ffe cts o f h ig h -d o se fe n ta n yl o n ca n in e re n a l fu n ctio n (R F ). W e a n e sth e tize d w ith so d iu m p e n to b a rb ita l (S P ) 1 6 d o g s, ra n d o m ly d ivid e d in to 2 g ro u p s: in G 1 , S P w a s g ive n a lo n e , a n d in G 2 , co m b in e d w ith 0 .0 5 m g .kg -1fe n ta n yl. A li a n im a is w e re ve n tila te d a rtificia lly a n d h a d ca th e te rize d le ft a n d rig h t fe m o ra l ve in s a n d le ft fe m o ra l a rte ry fo r flu id in fu sio n , d ru g a d m in istra tio n , b lo o d co lle ctio n , a n d h e m o d yn a m ic m e a su re m e n t. U rin e w a s co lle cte d th ro u g h o u t th e e xp e rim e n t. A ttrib u te s o f R F w e re stu d ie d . S P d id n o t a lte r R F , w h ich w a s sig n ifica n tly a lte re d b y fe n ta n yl. In G 2 , slo w e r h e a rt ra te s, m e a n a rte ria l p re ssu re , cre a tin in e cle a ra n ce , u rin a ry o u tp u t, o sm o la r c1 e a ra n ce a n d fra ctio n a l e xcre tio n o f so d iu m a n d p o ta ssiu m w e re o b se rve d . G 1 h a d a b e h a vio r a ttrib u te d to e x tra c e llu la r vo lu m e e xp a n sio n a n d n o R F a lte ra tio n s. In G 2 , w e o b se rve d sig n ifica n t d e cre a se s in R F d u e to o p io id -in d u ce d
h e m o d yn a m ic ch a n g e s, n o t d isca rd in g th e p o ssib le a ctio n o f a ld o ste ro n e . .
U N IT E R M S : H ig h -d o se fe n ta n yl. R e n a l fu n ctio n . O o g .
IN T R O O U C T IO N
H
i g h - d O S efe n t a n y l a n e s t h e s i a i s o f t e n u s e d b e c a u s e t h i s t e c h n i q u e i s u s u a l l y a s s o c i a t e d w i t h a s t a b l e c a r d i o v a s c u l a r h e m o d y n a m i c c o u r s e . H o w e v e r , t h e r e a r e f e w r e p o r t s o n t h e e f f e c t s o f h i g h - d o s e f e n t a n y l o n r e n a l f u n c t i o n ( R F ) a n d a u t h o r s h a v e n o t o b t a i n e d s i m i l a r r e s u l t s , p e r f o r m i n g t h e i r s t u d i e s o n m a n a s w e l l a s o n d o g s .t-4 F e n t a n y l h a s a l s o b e e n u s e d i n c o m b i n a t i o n w i t h o t h e r d r u g s k n o w n t o a l t e r R F .
T h e p r i m a r y a i m o f t h i s s t u d y i s t o r e p o r t t h e r e n a l r e s p o n s e o f d o g s t o a h i g h d o s e o f f e n t a n y l . T h e s e d o g s w e r e c o m p a r e d t o a r e f e r e n c e g r o u p r e c e i v i n g s o d i u m p e n t o b a r b i t a l ( S P ) , a d r u g w h i c h d o e s n o t a l t e r R F .5
, 6
A n d d re ss fo r co rre sp o n d e n ce :
P ro fa . O ra . Y a ra M a rc o n d e s M a c h a d o C a s tig lia D e p tº d e A n e s te s io lo g ia d a F M B - U N E S P D is trito d e R u b iã o J u n io r - C a ix a P o s ta l 5 3 0 B o tu c a tu /S P - B ra s il- C E P 1 8 6 1 8 -9 7 0
M A T E R IA L A N O M E T H O O S
A n e s t h e s i a w a s i n d u c e d i n 1 6 h e a l t h y m a l e m o n g r e l d o g s ( 8 t o 2 0 k g ) w i t h 3 0 m g . k g -t o f S P . I n t h e f i r s t e x p e r i m e n t a l p h a s e , a n e s t h e s i a w a s m a i n t a i n e d w i t h S P ( 5 m g . k g -t
). I n t h e s e c o n d p h a s e , a n i m a I s w e r e r a n d o m l y d i v i d e d i n t o 2 g r o u p s o f 8 d o g s a n d w e r e d i f f e r e n t i a t e d a s f o l l o w s :
G r o u p 1 ( G l ) - c o n t r o l g r o u p , m a i n t e n a n c e w i t h S P o n l y , a n d ;
G r o u p 2 (G 2 ) -m a i n t e n a n c e w i t h S P a n d 0 . 0 5 m g . k g -t f e n t a n y l .
A c u f f e d e n d o t r a c h e a l t u b e w a s i n s e r t e d , a n d t h e a n i m a I s r e c e i v e d p a n c u r o n i u m b r o m i d e ( 0 . 0 8 m g . k g -t i n t h e f i r s t d o s e a n d 0 . 0 3 m g . k g -t f o r m a i n t e n a n c e ) . V e n t i l a t i o n w a s c o n t r o l l e d b y a K . T a k a o k a m o d e l 6 6 0 a p p a r a t u s w i t h r o o m a i r a n d a d j u s t e d t o m a i n t a i n n . o r m a l b l o o d - g a s p r e s s u r e s . L e f t . a n d r i g h t f e m o r a l v e i n s w e r e c a t h e t e r i z e d f o r f l u i d i n f u s i o n , d r u g s a d m i n i s t r a t i o n , b l o o d c o l l e c t i o n a n d m e a s u r e m e n t o f i n f e r i o r v e n a c a v a p r e s s u r e ( I C P ) . C h a n n e l i z a t i o n o f t h e l e f t f e m o r a l a r t e r y w a s c a r r i e d o u t f o r m e a s u r e m e n t s o f m e a n a r t e r i a l p r e s s u r e ( M A P ) ( H g m a n o m e t e r ) . U r e t h r a l c a t h e t e r i z a t i o n w a s p e r f o r m e d .
C A S T IG L lA , Y .M .M .; B R A Z , J.R .C .; V IA N N A , P .T .G .; L E M O N IC A , L .; V A N E , L .A . - E ffe ct o f h ig h -d o se fe n ta n yl o n re n a l fu n ctio n in d o g s
• •
•
During the first phase, the animaIs received Ringer's
solution ( 0.4 ml.kg-l.min-l - extracellular volúme
expansion) for 30 min, followed by a prime dose of 30
mg.kg-l creatinine and 4 mg.kg-l para-aminohipuric acid
(PAH). Immediately afterwards, a solution ofO.15 percent
creatinine and 0.06 percent PAH in Ringer ( 0.6
mg.kg-l.min-I creatinine and 0.24 mg.kg-I.min-l PAH) was
administered by continuous drip infusion with a Gilson
pump model Hpl, until the end of the experimento There
were 4 clearance periods, each lasting 15 mino
Forty-five min after prime, the first clearance period
began with V measurement (always after emptying the
bladder), venous blood cOllection and determinations of
MAP, ICP, and heart rate (HR). After the first clearance
period end, the second phase of the experiment started
with the second clearance period immediately after
fentanyl administration. The third clearance period began
immediately after the end of the second, and the fourth
started 30 min after the end of the third.
The bladder was emptied and urine always collected
at the end of each period. Blood samples were collected
in the middle of each period. The mean values of the
readings were calculated from those obtained at the
beginning and end of each clearance period. The following
attributes were recorded:
• Hemodynamics - HR, MAP, ICP,. PAH
clearance (Cp A H) , renal blood flow (RBF) and
renal vascular resistance (RVR);
Blood - hematocrit (Ht)and plasma osmolarity
(Posm;
Renal function - creatinine clearance (C
cr)'
filtration fraction (FF), urinary output
(V),urinary osmolarity (Uosm)' osmolar
clearance (Cosm)' free water clearance (CH 2 0) ,
and fractional excretion of sodium (Na) and
potassium (K)(FENa and FEK).
The attributes were studied at the following times:
• 1st phase: Ml, control time for each animal
obtained 45 min after prime of creatinine and
PAH;
2nd phase: M2, immediately after the end of
Ml; M3, immediately after M2; M4, 30 min
after the end of M3.
In G2, M2, M3 and M4 were obtained immediately,
15 and 60 min after fentanyl administration.
PS and pancuronium maintenance dose was carried
out 30 min before Ml and M4.
All serum and urine samples were later assayed for
creatinine and PAH concentrations using colorimetric
techniques.7
,8 Osmolarity was obtained through cryoscopic
lowering. Na and K leveIs were determined using a flame
photometer with oxyacetylene.
From this information, the following were derived:
clearance (C)
=
U.VIP where U and Pare the urine andplasma substance concentration (mg.ml-l); FF
=
Ccr/C
p A H;Cosm= UosmVIPosm'· C '= V - C ; FE = C / C x 100;
H 2 0 osm cr
RBF
=
C / (I-Ht); and RVR=
MAP / RBF.PAH
f.l
Statistical analysis was carried out using the pro 1e
analysis.9,lO For attributes presenting a high coefficient of
variation (greater than 40 percent), the transformations
were studied according Kempthorne.ll A value of p
<
0.05 was considered statistically significant. The
a
prefixed was 0.05.
R E S U L T S
Among the hemodynamics attributes of Gl, MAP
(Fig. 2) was higher at M4 and Cp A H was lower at M4. With
respect to RF, V (Fig. 4) increased from M2 to M3 and
M4. Uosm(Fig. 5) decreased from Ml on, CH 2 0 (Fig. 7)
increased from Ml on, and FENa and FE
K (Figs. 8, 9)
increased from M2 to M4 (Table 1).
In comparison with the baseline valuss, HR (Fig. 1)
and MAP (Fig. 2) decreased immediately after 0.05
mg.kg-Iof fentanyl (G2). All values of C
cr' V, Cosm'FENa and FEK
(Figs. 3, 4, 6, 8, 9) decreased after fentanyl. On the other
hand, all values of CH 2 0 increased from M2 onwards (Table
1). There were no consistent changes in any of the
remaining attributes over the experimental period.
D I S C U S S I O N
SP is a useful agent to induce and maintain anesthesia
for experimental research and does not produce significant
RF changes.5
,6 In small- to medium-sized dogs, such as
the ones we used, HR is between 60-120 beats per minute.1 2
In our study, the early observed increase in HR was
attributed to a sympatheticl3 or vagolytic 1 4origin or reflex
through the arterial baroreceptor.1 5
The increase in MAP only at M4 was probably due
to a superficial anesthesia leveI. Greater sympathetic
activity as well as an increase in RVR (not significant)
and a decrease in Cp A H (is actually indexed to renal plasma
flow) may have occurred from M3 to M4. The large
extracellular volume expansion performed in order to
obtain high urinary output and more reliable results of Cp A H
and Ccr actually resulted in high V. Examination of the
literature shows that the observed hemodynamic changes
1 4 3 5
T a b le 1
H e m o d yn a m ic a n d re n a l fu n ctio n a ttrib u te s [m e a n (5 0 )] in G 1 (co n tro l) a n d G 2 (fe n ta n yl).
*p < 0 .0 5
H R
=
h e a rt ra te ; M A P=
m e a n a rte ria l p re ssu re ; IC P=
in fe rio r ve n a ca va p re ssu re ; Cp A H=
P A H cle a ra n ce ; R B F=
re n a l b lo o d flo w ; R V R=
re n a l va scu la r re sista n ce ; C=
cre a tin in e c1 e a ra n ce ; V=
u rin e o u tp u t; U=
u rin a ry o sm o la rity; C=
o sm o la r c1 e a ra n ce ; C :2 0=
fre e w a te r cle a ra n ce ; F E=
fra ctio n a i~ xcre tio n . M 1=
co n tro lO ~ o m e n t (G 1 a n d G 2 );M 2
=
im m e d ia te ly a fte r fe n ta n yl (G 2 ); M 3=
1 5 m in a fte r fe n ta n yl (G 2 ); M 4=
6 0 m in a fte r fe n ta n yl (G 2 ).0 .4 1 (0 .1 7 ) 0 .3 9 (0 .1 6 ) 0 .3 5 (0 .1 2 ) 0 .5 1 (0 .1 8 )
0 .4 4 (0 .2 2 ) 0 .3 5 (0 .2 0 ) 0 .3 6 (0 .2 3 ) 0 .3 8 (0 .1 6 )
2 2 .5 (1 6 .4 ) 2 3 .6 (1 3 .1 ) 3 2 .2 (1 7 .3 )* 4 2 .7 (2 9 .6 )* 2 5 .4 (1 2 .6 ) 1 7 .6 (9 .3 )* 1 5 .2 (7 .8 )* 2 7 .6 (1 7 .3 )
M 4
1 4 6 (2 3 )
1 0 4 (3 1 )*
1 2 1 (2 )*
8 2 (2 )*
5 .5 (2 .2 )
5 .8 (2 .0 )
1 4 (8 )
1 5 (7 ) 1 1 (6 )*
1 1 (4 )
3 .4 (1 .7 )
2 .9 (1 .4 )*
- 0 .9 (0 .7 )*
- 0 .5 (0 .4 )*
3 .7 (2 .4 )* 1 .8 (2 .5 )* 4 6 6 (2 2 5 )*
5 2 6 (1 1 1 )
3 .2 (2 .0 )*
1 .3 (0 .9 )*
M 3
1 5 0 (1 8 )
1 0 7 (2 5 )*
1 1 2 (2 )
7 6 (2 )*
1 6 (5 )
1 3 (7 ) 5 .4 (2 .3 )
5 .7 (2 .4 )
2 0 (9 )
1 9 (1 1 )
3 .8 (1 .3 )
3 .2 (1 .5 )*
3 .2 (1 .8 )* .
1 .4 (1 .8 )* 5 0 6 (1 9 6 )*
5 6 0 (1 2 5 )
3 .2 (1 .8 )*
1 .3 (1 .1 )*
M 2
1 4 5 (1 9 )
1 0 6 (2 4 )*
1 1 3 (2 )
8 2 (2 )*
1 4 (6 )
1 3 (6 ) 5 .5 (2 .3 )
5 .5 (1 .9 )
1 9 (1 0 )
1 9 (1 0 )
4 .0 (1 .3 )
2 .8 (1 .0 )*
- 1 .0 (0 .7 )* - 1 .1 (0 .7 )*
- 0 .6 (0 .5 )* - 0 .6 (0 .5 )* 5 5 0 (2 0 1 )*
5 5 6 (1 0 1 )
2 .2 (1 .3 )
1 .9 (2 .5 )* 2 .6 (1 .5 )
1 .5 (1 .1 )* M 1
1 4 4 (1 8 )
1 3 8 (3 5 )
1 1 4 (2 )
1 1 5 (3 )
1 4 (7 )
1 4 (8 ) 5 .4 (2 .2 )
5 .4 (2 .3 )
1 7 (1 1 )
2 0 (1 2 )
3 .7 (1 .1 )
3 .6 (1 .5 )
-1 .5 (1 .4 )
-1 .1 (0 .7 )
0 .0 9 (0 .0 6 ) 0 .1 0 (0 .0 6 ) 0 .1 4 (0 .0 8 )* 0 .1 5 (0 .0 9 )*
0 .1 3 (0 .0 9 ) 0 .1 1 (0 .0 9 )* 0 .0 9 (0 .0 8 )* 0 .0 8 (0 .0 8 )*
7 1 1 (2 8 3 )
5 7 8 (1 6 2 )
1 .8 (1 .1 )
3 .3 (4 .4 ) 2 .8 (1 .1 )
2 .5 (1 .8 )
H R (beats.m in-1 )
G ro u p 1
G ro u p 2
M A P (m m H g) G 1
G 2
IC P (cm H20 )
G 1
G 2
Cp A H (m l.m in-1.kg-1 ) G 1
G 2
R B F (m l.m in-1.kg-1 )
G 1
G 2
R V R (m m H g.m l-1.m in-1 )
G 1
G 2
C cr (m l.m in-1.kg-1)
G 1
G 2
F EN a (% )
G 1
G 2
F EK (% )
G 1
G 2
C
H 2 0 (m l.m in-1 ) G 1
G 2
-V (m l.m in-1.kg-1 ) G 1
G 2
U o sm (m O sm .kgH20-1) G 1
G 2
C o sm (m l.m in-1) G 1
G 2
a re sim ila r to th o se re p o rte d in
d o g s b y o th e r in v e stig a to rs.
T h e y o b se rv e d d e c re a se s in V
o n ly 1 5 m in a fte r th e in je c tio n
o f S Pin to d o g S .6 ,16 L o w e r U osm w a s a ttrib u te d to in c re a sin g .
v a lu e s o f V , w h ic h is n o t
e v id e n c e o f w a te rd iu re sis,
sin c e C H 20 increased, y e t
c o n tin u e d n e g a tiv e , a n d th e re
w a s a p ro g re ssiv e in c re a se in
C o sm ' F EN a a n d F EK •
G re a te r v e n o u s re tu m a n d
p re lo a d d u e to e x tra c e llu la r
v o lu m e e x p a n sio n c a u se a te ria l
d iste n tio n w ith lib e ra tio n o f
a rte ria l n a triu re tic p e p tid e ,
w h ic h h a s n a triu re tic a n d
d iu re tic a c tio n s. T h e re is
in p ib itio n o f v a so p re ssin
re le a se b y a rte ria l d iste n tio n
a n d a lso o f re n in re le a se b y
e x tra c e llu la r v o lu m e e x p a n sio n .
T h u s, w ith th e in c re a se in
e x tra c e llu la r v o lu m e , a s
e x p e c te d th e re w a s g re a te r
e lim in a tio n o f w a te r, a n d a lso
o f so lu te s.
T h e a d m in istra tio n o f
fe n ta n y l to th e w e ll-a n e sth e tiz e d
. d o g s o f G 2 re su lte d in ra p id
d e c re a se s in H R a n d M A P .
B e c a u se fe n ta n y l h a s n o
sig n ific a n t d ire c t p e rip h e ra l
c a rd io v a sc u la r e ffe c ts, th e H R
d e c re a se m u st h a v e b e e n d u e to
a c e n tra l e ffe c t - a re d u c tio n o f
e ffe re n t n e u ro g e n ic a n d h u m o ra l
sy m p a th e tic to n e . It fo llo w s th a t
th e h ig h e r th e p re e x istin g
sy m p a th e tic a c tiv ity , th e g re a te r
th e p o ssib ility fo r c a rd io v a sc u la r
d e p re ssio n fro m fe n ta n y l.l7
H o w e v e r, th e m e c h a n ism
in v o lv e d m a y b e b ra d y c a rd ia
c a u se d b y fe n ta n y l m e d ia te d b y
v a g o .1S-2 0
H y p e rte n sio n se e m s to b e
d e p e n d e n t o n a c tio n o n
sy m p a th e tic ,n e rv te rm in a ls,2 1 o r
fe n ta n y l m a y e v e n lo w e r th e
p la sm a le v e Is o f te c h o la m in e s 1 7 ,2 2
C A S T IG L lA , Y .M .M .; B R A Z , J.R .C .; V IA N N A , P .T .G .; L E M O N IC A , L .;-V A N E , L .A . - E ffe ct o f h ig h -d o se fe n ta n yl o n re n a l fu n ctio n in d o g s
th ro u g h a c e n tra l e ffe c t - a re d u c tio n in e ffe re n t n e u ro g e n ic
to n e a n d h u m o ra l s y m p a th e tic to n e . H o w e v e r, P ria n o4
b e lie v e s fe n ta n y llib e ra te s c a te c h o la m in e s fro m th e a d re n a l
m e d u lla a n d p e rip h e ra l n e rv e s b y c e n tra l m e d ia tio n , w h ic h
m a y e x p la in th e in c re a s e h e o b s e rv e d in th e R V R o f d o g s
to w h ic h o n ly fe n ta n y l (2 5 a n d 5 0 flg .k g -I) h a d b e e n
a d m in is te re d . R e s u lts d iffe rin g fro m th e s e m a y b e d u e to
th e p re v io u s a d m in is tra tio n o f o th e r d ru g s s u c h a s
b a rb itu ra te s , w h ic h c a u s e c e n tra l d e p re s s io n a n d
s y m p a th e tic in h ib itio n .
T a n e y a m a e t a l.,2 3 in a d e n e ry a tio n s tu d y p e rfo rm e d
in d o g s , re p o rte d th a t th e re d u c tio n o f M A P p ro d u c e d b y
fe n ta n y l m a y b e m a in ly d u e to th e re d u c tio n o f s y m p a th e tic
o u tflo w . F la c k e e t a l.l
? d e m o n s tra te d th a t fe n ta n y l a lo n e d e c re a s e d p la s m a c a te c h o la m in e le v e Is , w h ic h m ig h t
in d ic a te lo w e r s y m p a th e tic n e rv e a c tiv ity . T h e d e c re a s e d
M A P in G 2 m a y h a v e c a u s e d lo w e r g lo m e ru la r c a p illa ry
h y d ro s ta tic p re s s u re a n d th u s re d u c in g Cc r' w h ic h is a n e s tim a tio n o f g lo m e ru la r filtra tio n ra te (G F R ). G F R
in flu e n c e s u rin e o u tp u t m o re th a n a n y o th e r o n e fa c to r.
H R ( b p m )
M A P (m m H g )
M l M 2 M 3
M o m e n ts
M 4
G ro u p s
. G l
. G 2
M l M 2 M 3
M o m e n ts
M 4
G ro u p s
. G l
. G 2
F ig u re 1 - H e a rt ra te in G 1 (S P ) a n d G 2 (fe n ta n y l) F ig u re 2 - M e d iu m a rte ria l p re s s u re in G 1 (S P ) a n d G 2 (fe n ta n y l)
Cc r (m I.m in -1 .k g -1 )
6 .
0 .3 0 .
V (m l.m in -t .k g -1 )
0 .4 0 .
M 4
G ro u p s
. G l E illJG 2
M 2 M 3
M o m e n ts M l
M 4 G ro u p s
. G l
. G 2
M 2 M 3
M o m e n ts
M l
o
15
3
2 4
F ig u re 3 - C re a tin in e c le a ra n c e in G 1 (S P ) a n d G 2 (fe n ta n y l) F ig u re 4 - U rin a ry o u tp u t in G 1 (S P ) a n d G 2 (fe n ta n y l)
1 4 3 7
900 .
C o sm (m l.m in -1)
6 .
800 5 .
M 4
G ro u p s
.G l
R G 2
M 2 M 3
M o m en ts
M l
o
1 4
3
F igure 6 - O sm olar clearance in G 1 (S P ) and G 2 (fentanyl)
2
M 4
M 2 M 3
M o m en ts
M l
G ro u p s
.G l
E lG 2
F igure 5 - U rinary osm olarity in G 1 (S P ) and G 2 (fentanyl)
C 8 2 0 (rn l.rn in -1 )
- 2 .
7 _ .
M 4 M 3
M 2
M l - 1
5
1 3
M 4
M 3
M 2
M l -1
-3
M o m en ts
G ro u p s.G l .G 2
M o m en ts G ro u p s
.G l ErnG 2
F igure 7 - F ree w ater clearance in G 1 (S P ) and G 2 (fentanyl) F igure 8 - S odium fractional excreption in G 1 (S P ) and G 2 (fentanyl)
T h ere are tw o m ain m ech an ism s resp o n sib le fo r th e
p reserv atio n o f ren al p erfu sio n in th e p resen ce o f a
d ecreased b lo o d p ressu re. F irst, th e n o rm al k id n ey
au to reg u lates its b lo o d flo w , k eep in g an alm o st co n stan t
R B F w ith in a M A P ran g e o f 8 0 - 1 8 0 m m H g . T h e seco n d
p o ssib le m ech an ism is th e in traren al secretio n o f
p ro stag lan d in s P G E 2 an d P G I2. B o th are p o ten t
v aso d ilato rs.2 4
O u r d ata su g g est th at th ese tw o resp o n ses m ay b e
p reserv ed d u rin g h ig h -d o se fen tan y l-in d u ced h y p o ten sio n .
C
p A H an d R B F d id n o t ch an g e an d R V R w as o n ly slig h tly
(an d n o t sig n ifican tly ) red u ced , d esp ite a m ark ed d ecrease
in p erfu sio n p ressu re. T h u s, th e sig n ifican t d ecrease o f
G F R (C c) p o ssib ly w as m in im ized .
F en tan y l, a
Jl
o p iate recep to r ag o n ist, d im in ish es Vin th e d o g .,,2 T h is effect, co m m o n to m o st o p iates, h as
b een attrib u ted to th e stim u latio n o f v aso p ressin (an
an tid iu retic h o rm o n e) release.2 5 M o re recen t ev id en ce
su g g ests th at th is is n o t th e d ecisiv e facto r, alth o u g h in
th is stu d y m ed iated , m ay b e a red u ctio n in G F R .2 6 ,2 7
In o u r stu d y , M A P an d Ccr d ecreased in G 2 , w h ile
Cp A H an d R B F d id n o t. H o w ev er, G R F b eg in s to d ecrease
at h ig h er ren al p erfu sio n p ressu re th an R B F . A s d iu resis
is g o v ern ed m ain ly b y tw o p h y sio lo g ical m ech an ism s - b y
C A S T IG LlA , Y .M .M .; B R A Z , J.R .C .; V IA N N A , P .T .G .; LE M O N IC A , L.; V A N E , L.A . - E ffect of high-dose fentanyl on renal function in dogs
6 0 .
Figure 9 - Potassiumfractional excreption in G 1 (8 P) and G2 (fentanyl) FEK(O ~)
80 - .
CONCLUSIONS
A C K N O W L E D G E M E N T : W e th a n k P ro f. D r. P a u lo
R o b e rto C u ri fo r sta tistic a I a d v ic e a n d a n a ly sis.
In th e p o p u la tio n o f d o g s w h ic h re c e iv e d o n ly S P ,
th e o b se rv e d b e h a v io r c a n b e a ttrib u te d to e x tra c e llu la r
v o lu m e e x p a n sio n . T h e se a n im a Is w e re c o m p a re d to o th e rs
re c e iv e d h ig h -d o se fe n ta n y l. T h e re w e re sig n ific a n t
d e c re a se s in R F , p ro b a b ly d u e to sig n ific a n t o p io id -in d u c e d
h e m o d y n a m ic c h a n g e s. H o w e v e r, w e c a n n o t e lim in a te th e
p o ssib ility o f m a in a c tio n d u e to a ld o ste ro n e .
A n o th e r fa c to r a ffe c tin g re n in -a n g io te n sin a c tiv ity
is th e p ro sta g la n d in sy ste m . T h e se m a te ria Is a re
sy n th e siz e d fro m fa tty a c id s a n d a re se c re te d b y th e re n 'a l
m e d u lla . A p a rt fro m b e in g d ila to rs o f th e re n a l v a sc u la tu re ,
th e y p ro d u c e re n in re le a se b u t e n h a n c e so d iu m e x c re tio n
b y th e tu b u le s. O n th e c o n tra ry , o u r d a ta d e m o n stra te th a t
F E d im in ish e d a fte r fe n ta n y l a d m in istra tio n .
N a
P ro sta g la n d in s c a n a lso b e re le a se d fro m th e k id n e y b y
a n g io te n sin a n d n o re p in e p h rin e a n d u n d e r a
v a so c o n stric tiv e sta te (h y p o te n siv e ). 24
In c o n tra st to w h a t h a p p e n e d in G 1 , N a a n d K o u tp u t
d e c re a se d . A ld o ste ro n e n o rm a lly e n h a n c e s N a
re a b so rp tio n a n d K se c re tio n b y th e d ista I tu b u le . H o w e v e r,
th e re is n o m a n d a to ry c o u p lin g b e tw e e n th e se c e llu la r
m e c h a n ism s. In o th e r w o rd s, th e N a a m o u n t in th e d ista I
lu m e n tu b u le is n o t a lim itin g fa c t~ r to K se c re tio n , a n d
th e re is n o o b se rv e d o n e -to -o n e e x c h a n g e b e tw e e n N a a n d
K a t th is n e p h ro n le v e I. F o r th is re a so n , o u r re su lts a re
c o n siste n t w ith a ld o ste ro n e h a v in g a n im p o rta n t e ffe c t o n
G ro u p 2 .
G ro u p s
.G l
. G 2 M 4
M 2 M 3
M o m e n ts
M l
o
re g u la tio n o f th e R B F a n d G F R (Cc r)' a n d b y v a ria tio n o f
tu b u la r re a b so rp tio n - th e se a lte ra tio n s w o u ld a lre a d y b e
c o n trib u tin g to re d u c in g V (a s o b se rv e d in G 2 ).
S in c e sta b iliz a tio n o f U fo llo w e d e a c h
o sm
e x p e rim e n ta l p e rio d (in c o n tro I g ro u p U o sm d e c re a se d a ll
tim e ), it is p o ssib le th a t th e re w a s re te n tio n o r w a te r a n d
a lso o f so lu te s, b e c a u se Co sm d e c re a se d a fte r fe n ta n y I. CH20
d id n o t c h a n g e a fte r th e fe n ta n y I d o se (in G 1 , it in c re a se d ).
T h e se fa c ts su g g e st a ld o ste ro n e a c tio n . T h e
h y p o te n sio n w o u ld h a v e a c tiv a te d th e re n in a n g io te n sin
-a ld o ste ro n e sy ste m ; th e e n d p ro d u c t o f re n in re le a se is th e
p ro d u c tio n o f a n g io te n sin 11, w h ic h in tu rn stim u la te s
a ld o ste ro n e re le a se . A ld o ste ro n e im p a c ts o n re n a l sa lt a n d
w a te r re te n tio n ; it in c re a se s d ista I tu b u la r re a b so rp tio n o f
so d iu m , w h ic h d e c re a se s w a te r e x c re tio n . T h u s, in o u r
stu d y , V d e c re a se d a fte r fe n ta n y I a d m in istra tio n , a n d u rin e
p re se n te d sta b le o sm o la rity .
4 0
20
0lljetivos: Estudamos os efeitos de alta dose cjefentahil (F) <erTJ<a.tributosdefunção renal (FR)do cão. Desenho: Anestesiamos
'Rom
pentobarbital sódico (P8).16c~e~ divididos.?lea!oriarp~ptE3<r<m2grupos: mélnutenção. comP8 (G 1) e P8 com F (0,05rng.kg-1
) (G2). Intervenção: .~scães for~rn.YE3~tilad?sar~ifi.p.ialrnent7.e tiveram9~teteri<zéldas as veias f~morais esquerda e
direita e a artériafemoralesquerda para infysªo <g~dr.?g~$<~çol<tt~qe dado.s he~odin~mic9se de sangue para dosager)s
laboratoriais. Coletou-se urina durante todo' experimento.\tv'lensuraçã9: DeterminararTl,-se os valores. de atributos de FR ..
Resultados: P8 não mudou a FR e o comportamento dErG1>deveu~se à expansão do volumeextracelular. O F diminuíu
significativamente freqüência cardíaca, pressão arterial média, "clearance" de creatininél, volume urinário, "clearance" osmolar
e excreção fracionária de sódio e potássio. Conclusões: A diminuição da FRfoiprovavelmente devida às alterações
hemodinâmicas induzidas pelo ~ não se. descartando possível ação da aldosterona.
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