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Hernia (1999) 4:181-1,87
ernia
9 Springer-Verlag 1999
l t e r e d c o l la g e n s y n t h e s i s i n f a s c i a t r a n s v e r s a l i s o f p a t i e n t s w i t h i n g u i n a l h e r n i a
U . K l in g e I H . Z h e n g I Z . Y . S i R . B h a r d w a j 2 B . K l o s t e r h a l f e n 2 a n d V . S c h u m p e l i c k I
1The Surgica l De partment, 2The Inst i tute of Pathology, The Technica l U nivers i ty of Aachen (RWT H), Pauwelsstr . 30, D-52o57 Aachen, G ermany
S u m m a r y . T h e a i m o f th i s s t u d y w a s t o s u b s t a n t i a t e t h e h y p o t h e s i s a s t o w h e -
t h e r a n a l t e re d m e t a b o l i s m o f t y p e I a n d t y p e I I I c o ll a g e n s h o u l d b e i n c l u d e d
a s p a t h o p h y s i o l o g i c a l c o n s i d e r a t io n s o f i n g u i n a l h e r n i a d e v e l o p m e n t o r n o t .
T h e r e f o r e , f a s c i a t r a n s v e r s a l i s d e r i v e d f r o m p a t i e n t s w i t h i n d i r e c t h e r n i a s
( n = 9 ) , d i r e c t h e r n i a s ( n = 7 ) a n d f r o m c o n t r o l s ( n = 7 ) w e r e i n v e s t ig a t e d b o t h
b y i m m u n o h i s t o c h e m i s t r y a n d p r o t e i n a n a l y si s ( W e s t e rn B l ot ). B o t h i m m u -
n o h i s t o c h e m i c a l a n a ly s i s a n d W e s t e r n B l o t a n a l y s i s s h o w e d t h a t t h e r a t i o o f
t h e r e l a t iv e a m o u n t s o f t y p e I t o t y p e I I I c o l l a g e n w a s s i g n i f i c a n tl y d e c r e a s e d
i n t h e f a s c i a tr a n s v e r s a l is o f p a ti e n t s w i t h i n d i r e c t a n d d i r e c t i n g u i n a l h e r n i a s
c o m p a r e d w i t h c o n t r o l s ( p < o . o o l ) . T h e r e l a ti v e r e d u c t i o n o f t h e c o l l a g e n I /I I I
r a t io m a y b e e x p l a i n e d b y a c o n c o m i t a n t i n c r e a s e i n c o l l ag e n t y p e I II s y n t h e -
s i s i n b o t h h e r n i a - f a m i l i e s . I n c o n t r a s t t o t h e c o n t r o l g r o u p t h e r e w a s n o
s i g n i f i c a n t d i f f e r e n c e b e t w e e n p a t i e n t s w i t h d i r e c t a n d i n d i r e c t h e r n i a . I t i s
c o n c l u d e d t h a t t h e c h a n g e i n c o l la g e n t y p e I / I I I r a t io , w i t h t h e r e s u l t i n g a l te -
r e d p h y s i c a l p r o p e r t i e s , m i g h t e s s e n t i a l l y p r e d i s p o s e i n d i v i d u a l s to t h e d e v e -
l o p m e n t o f i n g u i n a l h e r n i a . T h u s , a n a l t e r e d c o l la g e n m e t a b o l i s m w o u l d p r o -
v i d e a n a d d i t i o n a l t h e o r e t i c a l b a s is f o r t h e u s e o f a l lo p l a s ti c m a t e r i a ls , s u c h a s
s u r g ic a l m e s h e s , a n d a n e x p l a n a t i o n f o r t h e d i s a p p o i n t i n g h i g h r e c u r r e n c e
r a t es a f t e r a p p r o p r i a t e p r i m a r y h e r n i a r e p a i r, p a r t i c u l a r l y i f m e s h - f r e e t e c h -
n i q u e s h a v e b e e n u s e d .
Key words : Co ll agen I - - Co l l agen I I I - - He rn i a - - Fa sc i a t r ansve r sa li s - - Surg i-
ca l me sh
Correspondance to: U. Klinge
Received February 12 1999
Accepted in fin al for m July 12 I999
W e l l k n o w n r is k f a c t o r s a s s o c i a t e d
w i t h h e r n i a t i o n i n t h e i n g u i n a l a r e a a r e
p r i m a r i l y a n o p e n p r o c e s s u s v a g i n a l i s
a n d r e p e a t e d e l e v a t i o n o f i n t r a -a b d o -
m i n a l p r e s s u r e . H o w e v e r , t h e s e c l a s si -
c a l d e s c r i p t io n s a n d p a t h o p h y s i o l o g i -
c a l c o n c e p t s d o n o t a c c o u n t f o r t h e i n i -
t i a l a p p e a r a n c e o f a n i n d i r e c t i n g u i n a l
h e r n i a a f t e r t h e a g e o f f o r t y [ C o n n o r
1 97 3] , o r f o r t h e t e n d e n c y o f e l d e r l y
p a t i e n t s t o h a v e a t t e n u a t e d f a s c i a l
s t r u c t u r e s [ P e a c o c k 1974 S t o p p a 1998]
a n d a n i n c r e a s e d i n c i d e n c e o f d i r e c t
i n g u i n a l h e r n i a s . M o r e o v e r , t h e y c a n -
n o t a d e q u a t e l y e x p l a i n t h e u n s a t i s f a c -
t o r y h i g h r e c u r r e n c e r a t e s o f i n g u i n a l
h e r n i a s a f t e r p h y s i c a l s t r e n g t h h a s
b e e n r e s t o r e d b y s u r g ic a l m e s h - f r e e
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182 U. Klinge,et ah Collagensynthesisand hernia
procedures [Lichtenstein 1993, Arlt
1997]. An essential condition for the
development of inguinal hernia is a
defect of the fascia transversalis. The-
refore its incision and repair is of spe-
cial importance for hernia repair with
regard to recurrence rate [Schumpelick
1994]. Pathological and biochemical
studies have demonstrated that
patients with inguinal hernia present
with a variable diameter and periodici-
ty of collagen fibrils [Nikolov
199o,
Read
1998],
a reduced collagen synthe-
sis, a diminished amount of polymeric
collagen, a lower rate of fibroblast pro-
liferation and a longer fibroblast gene-
ration time [Wagh
1971 ,
Ajabnoor
1992]. These factors correspond to an
increased elasticity of the transversalis
fascia [Pans
1997].
The tensile strength
of the tissue depends largely upon the
proportions of type I and III collagen
[Henke11982]. Type I essentially repre-
sents a mature, cross-linked collagen
with thick fibres predominantly seen
in tendons and ligaments, whereas
type III consists of thin, immature and
isolated collagen fibres, mainly found
in embryonic tissue and smooth
muscle [Dale 1996, Fleischmajer 1 9 8 1
Fleischmajer 199o]. In the present
s tudy immunohis tochemist ry and
Western Blot analysis of the type I and
III collagens were undertaken to deter-
mine whether an al teration of collagen
synthesis and a change of the type I /
type III ratio in fascia transversalis was
associated with the development of
inguinal hernias.
aterial and method s
Between November 1997 and July 1998,
a total of 23 patients participated in the
study following informed consent in
the Depar tment o f Surgery at the Rhe-
nish-Westphalian Technical Universi-
ty, Aachen, Germany. The patients
who underwent primary hernia repair
had either indirect inguinal hernias
(male=8, female=l) or direct inguinal
hernias (male=6, female=l). Patients
undergoing other abdominal opera-
tions where a fascial sample could be
taken in the lower abdomen acted as
controls (male=5, female=2). There
was no significant difference in age
between the three groups (indirect her-
nias: 64 years (54-72); direct hernias 68
years
5 5 - 7 7 ) ;
controls: 63 years
(42-79)).
Patients undergoing steroid thera-
py, with previous history of any abdo-
minal surgery, diabetes, abdominal
aortic aneurysm and connective tissue
diseases were excluded from the study.
The tissue samples obtained of fascia
transversalis were transferred to the
laboratory on ice immediately after
surgery. They were defatted and frozen
in liquid nitrogen and then kept at -7o~
until used.
Immunoh is tochemica lstud ies
For detecting type I and type III colla-
gen in fascia transversalis, 5 pm cryo-
stat sections were cut at -2o~ and pla-
ced on cleaned slides coated with Poly-
L-lysine (Sigma, USA), and fixed at 4~
in acetone for lo min. Endogenous
peroxidase activity in the tissue sec-
tions was blocked with 0.3 H202 in
methanol for 30 min. Mouse anti-
human type I collagen (Sigma, USA)
and Goat anti-human type III collagen
(Southern Biotechnology, USA) were
used as primary antibodies in a dilu-
tion of 1:5oo and 1:2oo, respectively.
These primary antibodies were incuba-
ted at room temperature for 1 h. Hor-
seradish peroxidase conjugated rabbit
anti-mouse antibody (Dako, Germany)
and rabbit anti-goat antibody (Dako,
Germany) were used as secondary
antibodies each at a dilution of 1:5o.
Sections were incubated with the
secondary antibodies at room tempe-
rature for 30 min. As a chromogen
0.06 3.3-diaminobenzidine tetrachlo-
ride was used. Finally, the sections
were dehydrated, cleared in xyline, and
mounted in Vitro-clud| (R. Langen-
brinck, Germany).
Half of the sections were additio-
nally counterstained with haematoxy-
lin. The intensity of the antigen-anti-
body reaction was quantified by an
image analyser system (Quantimet
6oo, Leica, Germany) using lO rando-
mised fields for each specimen.
Control sections were not incubed with
primary antibodies. In all cases the
control sections showed no evidence of
staining and colour reaction under
microscopic examination. The back-
ground control value was substracted
from the value obtained for each non-
control section. This protocol was
repeated three times for each tissue
sample.
Col lagenex t rac t i on
Tissue specimens for collagen extrac-
tion were cut into 1-2 mm 3 blocks.
After briefly washing in double distil-
led water, the tissues were suspended
for 30 min in double distilled water
containing proteinase inhibitors:
20 pM PMSF (Sigma, USA), 5 mM
EDTA, 1 pg/ml Leupeptin (Boehringer,
Germany), 5 pg/ml Aprotinin (Fluka
Schweiz). After pulverising, the colla-
gens were solubilized for 24 hs at 4~
using limited pepsin digestion
(1 mg/ml) in 0.5 M acetic acid, (pH 2.5),
with continuous vigorous stirring [Mil-
ler 1 9 8 2 ] . The mixtures were centrifu-
ged at 35,000 g, at 4~ for 45 min and
the supernatants collected and kept at
-2o~ The precip itates were then
resuspended in fresh o.5 M acetic acid
containing pepsin and again re-extrac-
ted. This procedure was repeated for
three t imes for each sample.
Crystalline sodium chloride (NaC1)
was slowly added to the combined
supernatants until the final concentra-
tion of NaC1 was 0.7 M. The samples
were then centrifuged at 4~ for 45 min
at 35,ooog. The supernatants contai-
ning the solubilized type I and type III
collagen were dialysed overnight
against o.1 M acetic acid at 4~ and
then lyophilized.
Electrophoresis and Weste rn l o t
Electrophoresis reagents and buffers
were prepared as described by Laemm-
li [197o]. 6.25 btg of protein (protein
essay (Bio-Rad, USA)) was loaded into
each well of a 6 polyacrylamide gel,
which was run in the stacking gel at
30 V and in the separating gel at loo
V. lO pl of biotinylated protein stan-
dards (Tropix USA) per lane was
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U. Klinge, et aI: Collagen synthesis and hern ia 183
Fig. la f
Imrnun ostain ing for collagen ty pe [ and type III in fascia transversalis, a collagen type I in groups with indirect h ernia; b collagen type I in patients wit h dire ct hernia; c coliagen ty pe I in
controls; d collagen t ype ll ~ n patients w ith indirec t hernia; e collagen typ e III in patients w ith direct hern ia; f collagen t ype III in controls; a f: 200 x
u s e d as s t a n d a r d . P r o t e i n s f r o m
s o d i u m d o d e c y l s u l p h a t e - p o ly a c r y l a -
mide ge l ele trophoresis SDS-PAGE)
were e lec t ropho re t ica l ly t r ansfe r red to
a p o l y v i n y l i d e n - d i f l u o r i d e P V D F )
me mb ran e Biorad , USA) by appl ica -
t ion of a cur ren t o f 0 .8 m A/cm ~ for 1 h
a t r o o m t e m p e r a t u r e . T h e W e s t e r n -
L i g h t P l u s C h e m i l u m i n e s c e n t d e t e c -
t ion sys tem Tropix | USA) was used
for the imm unologica l de tec t ion . Br ie -
f l y, n o n s p e c i f i c b i n d i n g s i t e s w e r e
b loc ke d w i th b loc k ing bu f f e r f o r 1 h .
T he m e m br a ne s w e r e i nc uba t e d w i th
m onoc tona l a n t i - hum a n c o ll a ge n type
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184 U. Klinge et al: Collage n synthesis and hern ia
I (Sigma, USA) and monoclonal anti-
human collagen type III (ICN Biomedi-
cals, Germany) at a dilution of 1:1.ooo
for 30 min, respectively. The mem-
branes were then incubated with a bio-
tinylated goat anti-mouse secondary
antibody at a di lution of 1:1o.ooo for 30
min, and subsequently incubated with
Avdix-AP conjugated at a dilution of
1:2o,ooo for 30 min. After 2x2 washing
in Assay buffer, a thin layer of CSPD
substrate solution was added to the
membranes, which membranes were
then exposed to x-ray film for 15-3o
min and visualised.
The relative amounts of type I and
type III collagen were determined by
Bio-Rad's Multi-Analyst| (Bio-Rad,
USA). A band of standard protein was
initially designated as a specific stan-
dard, following which the relative
values of protein bands corresponding
to collagen type I and type III within
the entire gel could be calculated inde-
pendently and automatically by the
software. Subsequently, the ratios of
the relative amounts of type I and type
III collagen were calculated and com-
pared with those of the control sub-
jects.
Statistical methods
Statistical analysis was c onducted
using Statistical Package for Social
Sciences (SPSS) software. Student's
two-tail t-test was used to determine
whether there were statistically signifi-
cant differences between either indi-
rect or direct inguinal hernia and
control and between indirect and
direct inguinal hernia. All data are pre-
sented as mean + SD (standard devia-
tion). Values of p
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u. K linge,et al: Collagensynthesisand hernia 185
p a t i e n t s w i t h i n d i r e c t a n d d i r e c t h e r -
n i a s c o m p a r e d w i t h t h e c o n t r o l s . A s a
r e su l t , t h e r a t i o s o f t y p e I t o t y p e I I I
c o l l a g e n w a s L o 9 + o . 2 7 i n t h e g r o u p
w i t h i n d i r e c t h e r n i a s a n d 1 .2 _+ o.3 3 i n
t h e g r o u p w i t h d i r e c t h e r n ia s , w h e r e a s
t h e t y p e I / I I I c o l l a g e n r a t i o w a s
1 .5 4 _+ o .3 2 i n c o n t r o l s ( F i g . 2 ) T h e r e
w e r e n o d i f f e r e n c e s b e t w e e n t h e i n d i -
r e c t a n d d i r e c t h e r n i a g r o u p s ( p > o . o 5 ).
T h e d e c r e a se i n t h e r a t i o o f t y p e I t o
t y p e I I I c o l l a g e n b o t h i n p a t i e n t s w i t h
e i t h e r i n d i r e c t oz" d i r e c t h e r n i a s , w a s
h i g h l y s i g n if i c a n t c o m p a r e d w i t h t h a t
i n th e c o n t r o l s ( p < o . o m ) .
W e s t e r n l o t a n a l y s i s a f c o l la g e n t y p e I
a n d t y p e I I I
T w o p r o t e i n b a n d s o f c o ll a g e n t y p e I,
( cu{I} ) an d (ot2{I} ) were de t ec t ed u s ing
6 % S D S - P A G E a n d W e s t e r n B l o t .
O t h e r p r o t e i n s b a n d s o f h i g h e r m o l e -
c u l a r m a s s c o r r e s p o n d i n g t o t h e b l ,
a n d g l , 1 c o m p o n e n t s o f c o l l a g e n w e r e
a l so d e t e c t e d ( F i g u r e 3 ) - T h e r e l a t i v e
c o n t e n t o f c o ll a g e n t y p e I w a s
1 1 9 . 3 6 + 2 4 . 3 8 % f o r t h e p a t i e n t s w i t h
ind i rec t he rn ia , 125 .o8+23.19% for t he
p a t i e n t s w i t h d i r e c t h e r n i a , a n d
121.73+31.o1% for the con trols .
I n c o n t r a s t c o l l a g e n t y p e I I I
cons i s t s o f t h ree c , l ( I I I ) cha ins . Unde r
r e d u c i n g c o n d i t i o n s , t h e i n t e r - c h a i n
d i su l p h i d e b o n d s o f c tl ( II I ) c h a i n s a r e
o p e n e d a n d r e s u l t i n t h e p r e s e n c e o f
c o n s t i t u e n t c h a i n s o f m o l e c u l a r w e i g h t
9 5 - 1 1 o k D a i n m o l e c u l e s r e s i d e n t s
wi th in the f ib r i l l a r aggrega tes (F ig . 4 ) .
T h e r e l a t i v e c o n t e n t o f c o l la g e n t y p e
I I I r e a c h e d 1 7 2 . 1 4 + 2 3 .6 2 % f o r t h e
p a t i e n t s w i t h in d i r e c t h e r n i a ,
2 2 1 . o 9 + 4 5 . 2 8 % f o r t h e p a t i e n t s w i t h
direc t her nia an d n3.51-+21.31% for th e
cont ro l s .
T h e r e s u l t s s h o w t h a t d u e t o a
p a r a l l e l i n c r e a s e i n t y p e I I I c o l l a g e n
sy n t h e s i s t h e r a t io s o f r e l a ti v e a m o u n t
o f t y p e I t o t y p e I I I c o l l a g e n f e l l t o
0 . 6- + 0. 0 7 i n i n d i r e c t h e r n i a s a n d
0 . 6 9 _ + o . o 9 i n d i r e c t h e r n i a s , w h e r e a s
t h e r a t i o w a s 1 . o 9 _ + o . a 8 i n c o n t r o l s
(F ig . 5 ). The re w ere no d i f fe rences be t -
w e e n i n d i r e c t :a nd d i r e c t h e r n i a s
( p > o . o s ) . H o w e v e r , t h e r a t i o o f t y p e I
a n d t y p e I I I c o l l a g e n i n p a t i e n t s w i t h
e i t h e r i n d i r e c t o r d i r e c t h e r n i a s w e r e
s i g n if i c a n tl y d i ff e r e n t w h e n c o m p a r e d
w i t h t h a t o f c o n t r o l s ( p < o . o m ) .
iscussion
I n y o u n g p a t i e n t s a n i n d i r e c t i n g u i n a l
h e r n i a u s u a l l y o c c u rs t h r o u g h a n u n o -
b l i t e ra t ed processus vag ina l i s , whereas
a d i r e c t i n g u i n a l h e r n i a a p p e a r s
t h r o u g h a w e a k a r e a ( t h e H e s s e l b a c h
t r i a n g l e ) b e t w e e n t h e p u b i c r a m u s a n d
t h e m u s c u l o f a s c i al c o m p o n e n t s o f th e
l o w e r a b d o m i n a l w a l l . I n t e r e s t i n g l y ,
o l d e r p a t i e n t s w i t h i n g u i n a l h e r n i a a r e
u su a l l y r e p o r t e d t o h a v e a d e f e c t in t h e
f a s c ia t r a n s v e r s a l i s [ P e a c o c k 1974
S c h u m p e l i c k 1 9 9 4 ] , r e g a r d le s s o f w h e -
the r i t i s media l o r l a t e ra l t o t he ep igas-
t r i c vessel s . Obvious ly , t he de fec t i n the
fasc i a t r ansve rsa l i s p l ays a p ivo ta l ro l e
i n t h e d e v e l o p m e n t o f h e r n i a s . T h u s , i n
h e r n i a l s u r g e r y i t s i n c i s i o n a n d a d e -
q u a t e m e c h a n i c a l r e p a i r i s o f p a r t i c u -
l a r i m p o r t a n c e i n r e g a r d t o l o w r e c u r -
rence ra t e s .
U n f o r t u n a t e l y , f e w p r e v i o u s s t u d i e s
h a v e f o c u se d m a i n l y o n t h e p a t h o l o g i -
ca l changes o f t he fa sc i a t r ansve rsa l i s .
A d j a c e n t t o t h e h e r n i a d e f e c t th e t r a n s -
v e r sa l i s f a s c i a i s k n o w n t o b e t h i n n e r
a n d a t t e n u a t e d [ P e a c o c k 1 9 7 4 ] . U l t r a -
s t r u c t u r a l s t u d i e s h a v e r e v e a l e d a p p a -
r e n t s t r u c t u r a l c h a n g e s i n t h e c o l l a g e n
a n d f i b r o b l a s t s [ N i k o l o v 1 9 9 o ] . F u r -
t h e r m o r e , a m a r k e d a t t e n u a t io n o f t h e
f a s c i a t r a n s v e r s a l i s a n d a s i g n i f i c a n t
r e d u c t i o n i n t h e t h i c k n e s s o f c o n n e c t i -
v e ti s su e h a s b e e n d e m o n s t r a t e d i n t h e
a r e a o f t h e i n g u i n a l r i n g o n t h e c l i n ic a l
n o r m a l s i d e o f p a t ie n t s w i t h i n g u i n a l
h e r n i a [ P e a c o c k 19741. I n o n l y o n e
s tudy , Be l ldn e t a l [1997] a n a l y se d t h e
t y p e I / I I I c o l la g e n r a t io i n t r a n sv e r sa -
l is f a s c i a o f p a t i e n t s w i t h i n d i r e c t a n d
d i r e c t h e r n i a a n d f o u n d n o s i g n i f i c a n t
d i f f e re n c e b e t w e e n t h e s e t w o g r o u p s .
T h e se d a t a a r e i n a c c o r d a n c e w i t h o u r
f i n d i n g s . F u r t h e r m o r e , i n t h e p r e s e n t
s t u d y , w e f o u n d t h a t t h e r a t i o o f th e
r e l at i v e a m o u n t o f t y p e I / I I I c o l l ag e n
i n t r a n s v e r s a l i s f a s c i a f r o m p a t i e n t s
w i t h e i t h e r i n d i r e c t o r d i r e c t i n g u i n a l
h e r n i a w a s s i g n i f i c a n t l y l o w e r t h a n
t h a t in c o n t r o l s ( p < o . o o l ) , b o t h b y
i m m u n o h i s t o c h e m i s t r y a n d W e s t e r n
Blo t ana lys i s . As Be l l6n obse rved the re
w a s n o d i f f e re n c e s b e t w e e n p a t i e n t s
w i t h i n d i r e c t a n d d i r e c t i n g u i n a l h e r -
n i a (p>o .o5) .
A l t h o u g h i m m u n o h i s t o c h e m i s t r y is
k n o w n t o b e l e s s e x a c t t h a n t h e W e s -
t e r n b l o t an a l y s i s , w h e n a l a n a l y s e d
c o l l a g e n r a t i o s w e r e c o n s i d e r e d t h e
t w o m e t h o d s s h o w e d a h i g h c o r r e l a -
t i o n w i t h a P e a r so n ' s c o r r e l a t i o n c o ef -
f i c ie n t o f r = o .7 9 ( p = o . o o 3 ) , i n d i c a t i n g
t h e p r o b a b l e su i t a b i l i ty o f i m m u n o h i s -
t o c h e m i s t r y f o r s c r e e n i n g i n v e st ig a -
t ions .
I n r e l a t i o n to t h e c o n t r o l g r o u p t h e
dec reased type I / I I I co l l agen ra t io in
h e r n i a p a t i e n t s w a s p a r a l l e l e d b y a
r e m a r k a b l e i n c r e a se i n t y p e I I I c o l l a -
g e n s y n t h e s i s . T h e s e r e s u l t s s u p p o r t
t h e f i n d i n g s o f F r i e d m a n e t a l [ 19 93 ],
w h o r e p o r t e d a m a r k e d i n c r e a s e i n
t y p e I I I c o l l a g e n m R N A e x p r e s s i o n
w i t h a p a r a l l e l d e c r e a s e i n c o l l a g e n
type I / I I I r a t io in f ib rob las t cu l tu res
o b t a i n e d f r o m t h e s k i n o f p a t i e n t s
u n d e r g o i n g h e r n i a ti o n .
I t is w e ll k n o w n t h a t t y p e I a n d t y p e
I I I c o l l a g e n c o e x i s t w i t h i n i n d i v i d u a l
f i b r i l s [ I i m o t o 1 9 8 8 ] , a n d t h a t t h e i r
r a t i o i s r e la t e d t o t h e d i a m e t e r o f t h e
co l l agen f ib r i l s [Da le 1996 , F l e i schma-
j e r 199o] . Type I co l l agen i s found as
d e n se b u n d l e s i n t i s su e s , su c h a s t e n -
d o n , l ig a m e n t s a n d d e r m i s . T h e s e
b u n d l e s c o n t a i n l a r g e - d i a m e t e r c o l la -
g e n f i b r i l s p r o v i d i n g su p e r i o r m e c h a -
n i c a l i n te g r i t y w h i c h t h u s d e t e r m i n e s
t h e s t r e n g t h o f t h e s e t i s s u e s . I n
c o n t r a s t t y p e I I I c o l l a g e n f o r m s t h i n
i so la t ed f ib r il s t ha t a re fo un d l a rge ly in
t i s s u e s t h a t r e q u i r e s o m e d e g r e e o f
f l e x i b il i ty a n d p l a s t i c i ty ( e . g. e m b r y o -
n i c s k i n , b l o o d v e s s e l s , a n d s m o o t h
musc le ) , and has a spec i f i c ro l e in the
d e t e r m i n a t i o n o f f ib r i l s tr u c t u r e , t i s su e
a r c h i t e c t u r e a n d f u n c t i o n [ D a l e 1 9 9 6 ,
Fleis chm ajer 1981, 199o].
I n g e n e r a l c o l l a g e n s t r e n g t h
d e c r e a se s w i t h i n c r e a s i n g f i b r e d i a m e -
t e r. T h e l a r g e d i a m e t e r f i b re s a r e m a d e
u p o f s m a l l e r f i b r i l s w i t h a g r e a t e r
c h a n c e o f f a i l u re b e c a u s e o f s l ip p a g e
b e t w e e n f i b r il s , r a t h e r t h a n b e c a u se o f
t h e b r e a k a g e o f c o l l a g e n m o l e c u l e s
[ A r m s t r o n g 1 9 9 2 ] . T h u s , t h e i n c r e a se
i n t y p e H I c o l l a g e n sy n t h e s i s d e t e c t e d
7/25/2019 Alteracion de Olageno en Fascia Transversalis
6/7
186 U. Klinge, et ah Collagen synthesis and hern ia
i n p a t i e n t s w i t h i n d i r e c t a n d d i r e c t
i n g u i n a l h e r n i a c a n r e s u l t i n a n i n c r e a -
s e i n s m a l l e r c o l l a g e n f i b r i l s w i t h a
c o n c o m i t a n t d e c r e a s e o f la r g e d i a m e -
t e r f i b r e s . T h i s m i g h t b e r e s p o n s i b l e
f o r t h e r e d u c t i o n i n m e c h a n i c a l s t r e n g -
t h a n d c h a n g e i n t h e p h y s i c a l p r o p e r -
t i e s o f t h e c o l l a g e n m a t r i x i n t h e a b d o -
m i n a l w a l l, a n d t h u s m a y p r e d i s p o s e
i n d i v i d u a l s t o t h e d e v e l o p m e n t o f
i n g u i n a l h e r n i a . T h i s h y p o t h e s i s i s
s u p p o r t e d b y th e f i n d in g s o f H u r m e
[ 9 9 ]
a n d L e h t o [ 1 9 85 ] f o r w o u n d h e a -
l i n g p r o c e ss e s . T h e y o b s e r v e d t h a t t h e
e a r l y sc a r t i ss u e f o r m a t i o n w i t h a p r e -
d o m i n a n t p r o p o r t i o n o f t y p e I II c ol la -
g e n i s q u i t e e l a s ti c a n d d o e s n o t c o n t r i -
b u t e s i g n i f i c a n t l y t o w o u n d t e n s i l e
s t r e n g t h . A c c o r d i n g l y , t h e g r e a t e s t
i n c r e a s e i n t e n s i l e s t r e n g t h i s o b s e r v e d
d u r i n g t h e l a t t e r s t a g e s o f h e a l i n g a n d
t i s s u e r e p a i r . T h i s c o r r e s p o n d s t o a n
i n c r e a s e o f ty p e I c o l l ag e n p r o d u c t i o n
a n d t h e f o r m a t i o n o f m o r e s t a b l e in t e r -
m o l e c u l a r c r o s s - l i n k s .
I n d i v i d u a l c o l l a g e n m o l e c u l e s a r e
h i g h l y o r g a n i s e d , w i t h t h e m e c h a n i c a l
p r o p e r t i e s o f c o l la g e n b e i n g d e p e n d e n t
u p o n c r o s s - l i n k s b e t w e e n c ~ - c h a i n s
w i t h i n a s i n g l e m o n o m e r a s w e l l a s
b e t w e e n c ~ - c h a i n s i n a d j a c e n t m o n o -
m e r s [ H e n k e l 1 9 8 2 ] . A s m o l e c u l e s o f
t y p e I a n d t y p e I I I c o l l a g e n h a v e t h e
s a m e l e n g t h a n d d i a m e t e r a n d b o t h
m o l e c u l e s c a n s u b s t i t u t e f o r o n e a n o -
t h e r i n c r o s s - l i n k e d p e p t i d e s , i t i s
c o n c e i v a b l e t h a t b o t h t y p e s o f m o l e -
c u l e s c a n f o r m m i x e d f i b r i l s w i t h i n f i -
n i t e ly v a r y in g p r o p o r t i o n s o f th e t w o
c o n s t it u e n t s. T h e p r o p o r t i o n o f ty p e
I I I c o l l a g e n i n m i x e d f i b r i l s m a y
d e p e n d d i r e c t ly u p o n t h e r a t i o o f t h e
s y n t h e s i s e d t y p e I a n d t y p e I I I c o l la g e n
m o l e c u l e s [ F l e i s c h m a j e r 1 98 1 ]. W i t h o u t
c r o s s - l i n k i n g t h e r e i s lo s s o f m e c h a n i -
c a l s t r e n g t h . I t h a s b e e n r e p o r t e d t h a t
i n c h r o n i c a l l y v o l u m e - o v e r l o a d e d a n d
c o n s e q u e n t l y h y p e r t r o p h i e d h e a rt s
t h e r e i s a n i n c r e a s e o f c r o s s - l i n k i n g
l o c a l i s e d o n t y p e I a n d t y p e I I I c o l la g e n
[ I i m o t o 1 9 8 8 ] . C o n s e q u e n t l y , a l t e r a -
t i o n s i n c o l l a g e n c r o s s - l i n k i n g is
t h o u g h t t o i m p a i r m y o c a r d i a l c o n t r a c -
t i l i ty [Capas so 1989] . Thus , an inc rease
o f ty p e I I I c o l la g e n m a y b e p r e d o m i -
n a n t l y r e s p o n s i b l e f o r t h e c h a n g e s o f
t h e g e o m e t r i c a l a r r a n g e m e n t o f c o l la -
g e n f i b r il s a n d o f c r o s s -l i n k s b e t w e e n
t y p e I a n d I I I c o ll a g e n . M o r e o v e r , t h e
o v e r a b u n d a n c e o f t y p e I I I c o ll a g en
r e l a t i v e to t y p e I c o l l a g e n c o u l d l e a d t o
a n i n c r e a s i n g i n so l u b l e, n o n - p o l y m e r i c
c o l l a g e n i n h i b i t i n g t h e a s s o c i a t e d p r o -
p e r t i e s o f t y p e I c o l l a g e n [ F r i e d m a n
1993].
A s a r e s u l t , t h e s e c h a n g e s c a n
c a u s e w e a k e n i n g o f t h e a b d o m i n a l w a l l
a n d p r o m o t e t h e d e v e l o p m e n t o f
i n g u i n a l h e r n i a .
I t is t h o u g h t t h a t e a r l y r e c u r r e n c e s
a f t e r a n t e r i o r m e s h - f r e e r e p a i r r e s u l t
f r o m t e c h n i c a l e r r o r s o r e x c e s s i v e t e n -
s i o n o n t h e s u t u r e l i n e c a u s e d b y t h e
a p p r o x i m a t i o n o f ti s su e . T h i s m i g h t b e
t r u e f o r e a r l y f a i l u r e s b u t c a n n o t
e x p l a in t h e a p p e a r a n c e o f r e c u r r e n c e s
s e v e r a l y e a r s a f t e r o p e r a t i o n . O u r f i n -
d i n g s i n d i c a t e t h a t t h e s e l a t e r e c u r -
r e n c e s m i g h t b e i n f l u e n c e d b y a d e f e c t
i n c o l l a g e n s y n t h e s i s w i t h t h i n n i n g o f
s c ar t is s u e a n d c o n t i n u e d i n h e r e n t
w e a k n e s s o f th e i n g u i n a l f l o o r [ L i c h -
t e n s t e i n 1993 A r l t 1997 F r i e d m a n
1993].
E v e n if n o n a b s o r b a b l e s u t u r e
m a t e r i a l i s u s e d i t h a s t o b e a s s u m e d
t h a t a f t e r a c e r t a i n t i m e t h e s e l o s e t h e i r
m e c h a n i c a l f u n c t i o n , w h i c h t h e n
d e p e n d s p u r e l y o n t h e t e n s i l e s t r e n g th
o f t h e i n d u c e d s c a r ti s s u e. A c c o r d i n g
t o o u r f i n d i n g s a n d t h e s e r e p o r t e d b y
o t h e r s , i t m a y b e i n f e r r e d t h a t t h e a l t e-
r e d c o l l a g e n m e t a b o l i s m s e e n i n f a s c i a
t r a n s v e r s a l i s m a y b e a g e n e r a l i s e d p h e -
n o m e n o n i n t h e s e p a t i e n t s , p e r h a p s
p r e d o m i n a n t l y i n t h e i n g u i n a l r e g i o n .
I f a s i m p l e m e s h - f r e e c l o s u r e i s p e r f o r -
m e d o r a n a u t o g e n o u s t i s s u e is a p p l i e d
i n t h e t r e a t m e n t o f p r i m a r y o r i n c i s io -
n a l h e r n i a i n t h e s e p a t i e n ts , a b n o r m a l
c o l l a g en m e t a b o l i s m m a y s t il l b e
d e t e c t e d i n t h e s k i n [ F r i e d m a n
19931
t h e r ec t u s s h e a t h [ W a g h
1971]
t h e
t r a n s v e r s a l i s f a s c i a [ N i k o l o v 1 9 9 o] a n d
t h e p e r i t o n e u m [ A j a b n o o r 1 9 9 2 ] o f t h e
i n g u i n a l r e g i o n . T h e r e f o r e , i t i s r e a s o -
n a b l e t h a t th e c o m p l e x m e t a b o l i c
a b n o r m a l i t i e s o f c o l l ag e n o f t h e s e t is -
s u e s w i ll d e c r e a s e t h e r e s i s t a n c e o f th e
a b d o m i n a l w a l l t o m e c h a n i c a l s t r e s s
a n d c o r r e s p o n d i n g h ig h r e c u r r e n c e
r a t e s s h o u l d t h e r e f o r e b e t h e p r e d e s t i -
n e d c l in i c a l r e s u l t o f p r i m a r y h e r n i a
r e p a i r . T h u s , o u r r e s u l t s s u p p o r t t h e
i d e a t h a t i m p l a n t a t i o n o f s u r g i c a l
m e s h e s s h o u l d l e a d t o a d e c r e a s e i n
r e c u r r e n c e r a t e s i n c o n d i t i o n s o f a n
a l t e r e d c o l l a g e n m e t a b o l i s m . T h e
n o n a b s o r b a b l e p o l y m e r ) m e s h e s
u s u a l l y s u p p o r t t h e t e n s il e s t r e n g t h o f
t h e a b d o m i n a l w a l l a f t e r c o r r e c t
i m p l a n t a t i o n . I n t h i s c o n t e x t i t a p p e a r s
r e a s o n a b l e t h a t t h e u s e o f a b s o r b a b l e
m e s h e s c a n n o t u s u a l l y p r e v e n t t h e
r e c u r r e n c e , b e c a u s e t h e i n d u c t i o n o f a
s c a r p l a t e a s a m e c h a n i c a l s t a b l e a n a t o -
m i c a l s t r u c t u r e a f t e r m e s h i m p l a n t a -
t i o n s e e m s t o b e d o u b t f u l i n p a t i e n t s
w i t h a l t e r e d c o l l a g e n d e p o s i t i o n a n d
c r o s s - l i n k i n g . P a r t i c u l a r l y i n t h e s e , a n d
i n o l d e r p a t i e n t s w i t h l a r g e d e f e c t s i n
t h e f a s ci a t r a n s v e r s a l i s o r r e c u r r e n t
h e r n i a s , t h e u se o f n o n a b s o r b a b l e
m e s h e s s e e m t o b e f a v o u r e d . N e v e r t h e -
l e ss , w i t h r e g a r d t o t h e p e r s i s t e n t f o r e i -
g n b o d y r e a c t i o n [ K l in g e 1999] a n d
s o m e o c c a s i o n a l l y s e v e r e c o m p l i c a -
t i o n s, s u c h a s m e s h m i g r a t i o n a n d f is -
t u l a f o r m a t i o n w i t h i t s u p t o n o w i n d e -
f i n i t e c u m u l a t i v e r a t e , t h e i r u s e s h o u l d
b e r e s t r i c t e d i n y o u n g p a t i e n ts .
I n c o n c l u s i o n , a s a r e s u l t o f i n c r e a -
s e d t y p e I I I c o l l a g e n s y n t h e s i s , t h e
r a t i o o f t y p e I / I I I c o l l a g e n i n t h e t r a n s -
v e r s a l i s f a s c i a f r o m p a t i e n t s b o t h w i t h
i n d i r e c t a n d d i r e c t h e r n i a s w a s s i g n i f i -
c a n t l y d e c r e a s e d i n c o m p a r i s o n t o
c o n t r o l s . T h e r a t i o i n p a t i e n t s w i t h
i n d i r e c t h e r n i a s w a s n o t s i g n i f i c a n t l y
d i f f e r e n t f r o m t h a t i n p a t i e n t s w i t h
d i r e c t h e r n i a s . T h e a l t e r a t i o n i n c o l l a -
g e n m e t a b o l i s m m a y f a v o u r t h e d e v e -
l o p m e n t o f h e r n ia s r e g a r d l e s s o f w h e -
t h e r t h e y a r e i n d i r e c t o r d i r e c t .
Acknowledgements.This work was supported by
a BMBF grant p roject no.
olKS95o3/9
for IZKF-
BIOMAT, RW TH-A achen.Moreover, he authors
gratefullyappreciate he personalgrants of Dr. H.
Zheng and Dr. Z.Y. Si suppo rted by E thicon
Ham burg, Germany.
7/25/2019 Alteracion de Olageno en Fascia Transversalis
7/7
U. Kl inge , e t a l : Col lagen synthe sis and her n ia 187
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