HIF CONCENTRATION AND HEART MUSCLE HISTOPATHOLOGY
1
Ba ck ground
P hysic a l exe rc ise is :
re gula r physic a l a c t ivit y pe rform e d in
c e rt a in pe riod of t im e a nd int e nsit y
a im s t o m a int a in t he body a lw a ys in good
c ondit ion of he a lt h a nd fit ne ss
re c om m e nde d for preve nt ive , c urat ive ,
a nd re ha bilit at ive progra m s in orde r t o
m a int a in a nd e nha nc e he a lt h, e spe c ia lly
t he he a lt h of t he c a rdiova sc ula r syst e m
2
Physic a l Ac t ivit ie s
Ae robic physic a l a c t ivit ie s
• ut ilize AT P e ne rgy ge ne ra t e d
by ox ida t ion proc e ss of
glyc oge n phosphor yla se a nd
fre e fa t t y a c ids.
• M e t a bolism proc e ss de pe nds
on ox yge n a va ila bilit y.
Ana e robic physic a l a c t ivit ie s
• Physic a l a c t ivit ie s t ha t do not
ut ilize ox yge n in t he m e t a bolism
proc e ss of e ne rgy produc t ion.
• T he e ne rgy is ge ne ra t e d by AT P
produc t ion origina t ing from
c re a t ine
phosphat e a nd
glyc oge n a s sourc e
3
•2 5 -3 0 % Ae robic
physic a l a c t ivit ie s
•7 0 -7 5 % Ana e robic
physic a l a c t ivit ie s
Sprint run c ha sing a
ba ll a nd hit t ing ba ll
w it h full pow e r a re
a na e robic physic a l
a c t ivit ie s
4
I f t he re is im pa ire d
he a r t func t ion a nd t he
ox yge n supply during
t he sprint c ould not
m e e t c a rdia c ox yge n
de m a nd
a c ut e he a r t
at t a ck
I
G
N
O
R
I
N
G
sudde n
de at h
5
Sudde n de at h in at hle t e s
fre que nt ly oc c urs during t he
c om pe t it ion
I t is a ssum e d t hat pe rfor m ing high
int e nsit y exe rc ise w it hout t a k ing re st
da ys for t he upc om ing c om pe t it ion ha s
gre at im pa c t in c a rdia c m uscle da m a ge
a nd sudde n de at h during t he
c om pe t it ion.
6
Sudde n de at h
if t he he a r t suc c e ssfully a da pt s
w it h such c ondit ion so t hat it m a y
c om pe nsat e t he loa d t a ke n during
physic a l exe rc ise .
T he re fore , t he c a rdio-prot e c t ive
e ffe c t exe r t e d by t he physic a l
exe rc ise c a n be a chieve d
N e e d t o unde rst a nd t he
m e cha nism of c a rdia c
a da pt at ion w he n w e
pe rfor m physic a l
exe rc ise s
7
T he m ole c ula r
a da pt at ion ???
H ypox ia ???
prot e c tion e ffe c t
on c a rdia c m uscle
VS
c a rdia c m uscle
c e ll da m a ge
?
Role of H I F-1 α
?
- Gluc ose m e t a bolism
- Angioge ne s is
8
Ba se d on t he a bove m e nt ione d ex pla nat ion, a
st udy should be pe rfor m e d, in orde r t o
re c ognize t he m e cha nism of m ole c ula r
a da pt at ion in c a rdia c m uscle during physic a l
exe rc ise w it h a loa ding of a e robic a nd
a na e robic physic a l a c t ivit ie s.
Ex pe rim e nt a l a nim a l m ode l is a n a ppropriat e
choic e t o deve lop t he m ole c ula r st udy; t hus,
t he ba sic m ole c ula r a da pt at ion of physic a l
a c t ivit ie s on t he c a rdiova sc ula r he a lt h c ould
be k now n
9
M at e ria l a nd M e t hods
Anim a l m ode l a nd inst rum e nt
• m a le Wist a r ra t s
• a ge d 6 -8 w e e k s
• w it h w e ight of 6 0 -1 0 0
gra m
Anim a l T re a dm ill for ra t
10
9 Groups
(P1 -P9 )
P 1 : t he c ont rol group
P2 -P9 : groups t ha t w e re
t re a t e d w it h
a e robic a nd
a na e robic
physic a l
a c t ivit y for 1 , 3 , 7
a nd 1 0 da ys
T he t re a t m e nt for physic a l a c t ivit y w a s pe rfor m e d
by put t ing t he ra t s on a nim a l t re a dm ill a nd se t t ing
t he t re a dm ill on t he spe e d ra t e of :
2 0 m /m inut e a bout 3 0 m inut e s (a e robic physic a l a c t ivit y)
3 5 m /m inut e a bout 2 0 m inut e s (a na e robic physic a l a c t ivit y)
11
12
13
T he obse r ve d a nd m e a sure d pa ra m e t e r
in t his st udy c ould be c a t e gorize d int o
2 groups of pa ra m e t e rs :
Pa ra m e t e rs on hypox ia :
m e a sure m e nt of H I F-1α
c onc e ntrat ion by ELI SA m e t hod
using k it of Sur ve yor T M I C
H um a n/M ouse Tot a l H I F-1α
I m m unoa ssa y
Pa ra m e t e r on a lt e re d
c a rdia c m uscle c e ll
st ruc t ure :
hist opa thologic a l
ex a m ina tion of c a rdia c
m uscle by H & E st a ining
14
RESU LT
15
Pa ra m e t e r on hypox ia
Konsentrasi HIF-1 Alpha
Kelompok Aerobik dan Anaerobik
KURVA STANDAR HIF-1 ALPHA
250
y = 0,002x + 0,0759
R2 = 0,9989
1
0,8
Konsentrasi HIF-1 Alpa
s e ra p a n p a d a 4 5 0 n m
1,2
0,6
0,4
*
150
1 Hari
3 Hari
7 Hari
10 Hari
Aerobik
116,03
96,13
49,46
49,03
Anaerobik
156,8
55,5
54,96
52,5
Kontrol
100
200
300
400
500
KONSENTRASI HIF-1 ALPHA (pg/mL)
600
Δ
50
0
0
*
100
0,2
0
*
200
Kontrol
45,7
Kelompok
T he c onc e nt ra t ion of H I F-1 α in he a rt m usc le t issue
* Signific a nt diffe re nc e c om pa re w it h c ont rol group (p
Ba ck ground
P hysic a l exe rc ise is :
re gula r physic a l a c t ivit y pe rform e d in
c e rt a in pe riod of t im e a nd int e nsit y
a im s t o m a int a in t he body a lw a ys in good
c ondit ion of he a lt h a nd fit ne ss
re c om m e nde d for preve nt ive , c urat ive ,
a nd re ha bilit at ive progra m s in orde r t o
m a int a in a nd e nha nc e he a lt h, e spe c ia lly
t he he a lt h of t he c a rdiova sc ula r syst e m
2
Physic a l Ac t ivit ie s
Ae robic physic a l a c t ivit ie s
• ut ilize AT P e ne rgy ge ne ra t e d
by ox ida t ion proc e ss of
glyc oge n phosphor yla se a nd
fre e fa t t y a c ids.
• M e t a bolism proc e ss de pe nds
on ox yge n a va ila bilit y.
Ana e robic physic a l a c t ivit ie s
• Physic a l a c t ivit ie s t ha t do not
ut ilize ox yge n in t he m e t a bolism
proc e ss of e ne rgy produc t ion.
• T he e ne rgy is ge ne ra t e d by AT P
produc t ion origina t ing from
c re a t ine
phosphat e a nd
glyc oge n a s sourc e
3
•2 5 -3 0 % Ae robic
physic a l a c t ivit ie s
•7 0 -7 5 % Ana e robic
physic a l a c t ivit ie s
Sprint run c ha sing a
ba ll a nd hit t ing ba ll
w it h full pow e r a re
a na e robic physic a l
a c t ivit ie s
4
I f t he re is im pa ire d
he a r t func t ion a nd t he
ox yge n supply during
t he sprint c ould not
m e e t c a rdia c ox yge n
de m a nd
a c ut e he a r t
at t a ck
I
G
N
O
R
I
N
G
sudde n
de at h
5
Sudde n de at h in at hle t e s
fre que nt ly oc c urs during t he
c om pe t it ion
I t is a ssum e d t hat pe rfor m ing high
int e nsit y exe rc ise w it hout t a k ing re st
da ys for t he upc om ing c om pe t it ion ha s
gre at im pa c t in c a rdia c m uscle da m a ge
a nd sudde n de at h during t he
c om pe t it ion.
6
Sudde n de at h
if t he he a r t suc c e ssfully a da pt s
w it h such c ondit ion so t hat it m a y
c om pe nsat e t he loa d t a ke n during
physic a l exe rc ise .
T he re fore , t he c a rdio-prot e c t ive
e ffe c t exe r t e d by t he physic a l
exe rc ise c a n be a chieve d
N e e d t o unde rst a nd t he
m e cha nism of c a rdia c
a da pt at ion w he n w e
pe rfor m physic a l
exe rc ise s
7
T he m ole c ula r
a da pt at ion ???
H ypox ia ???
prot e c tion e ffe c t
on c a rdia c m uscle
VS
c a rdia c m uscle
c e ll da m a ge
?
Role of H I F-1 α
?
- Gluc ose m e t a bolism
- Angioge ne s is
8
Ba se d on t he a bove m e nt ione d ex pla nat ion, a
st udy should be pe rfor m e d, in orde r t o
re c ognize t he m e cha nism of m ole c ula r
a da pt at ion in c a rdia c m uscle during physic a l
exe rc ise w it h a loa ding of a e robic a nd
a na e robic physic a l a c t ivit ie s.
Ex pe rim e nt a l a nim a l m ode l is a n a ppropriat e
choic e t o deve lop t he m ole c ula r st udy; t hus,
t he ba sic m ole c ula r a da pt at ion of physic a l
a c t ivit ie s on t he c a rdiova sc ula r he a lt h c ould
be k now n
9
M at e ria l a nd M e t hods
Anim a l m ode l a nd inst rum e nt
• m a le Wist a r ra t s
• a ge d 6 -8 w e e k s
• w it h w e ight of 6 0 -1 0 0
gra m
Anim a l T re a dm ill for ra t
10
9 Groups
(P1 -P9 )
P 1 : t he c ont rol group
P2 -P9 : groups t ha t w e re
t re a t e d w it h
a e robic a nd
a na e robic
physic a l
a c t ivit y for 1 , 3 , 7
a nd 1 0 da ys
T he t re a t m e nt for physic a l a c t ivit y w a s pe rfor m e d
by put t ing t he ra t s on a nim a l t re a dm ill a nd se t t ing
t he t re a dm ill on t he spe e d ra t e of :
2 0 m /m inut e a bout 3 0 m inut e s (a e robic physic a l a c t ivit y)
3 5 m /m inut e a bout 2 0 m inut e s (a na e robic physic a l a c t ivit y)
11
12
13
T he obse r ve d a nd m e a sure d pa ra m e t e r
in t his st udy c ould be c a t e gorize d int o
2 groups of pa ra m e t e rs :
Pa ra m e t e rs on hypox ia :
m e a sure m e nt of H I F-1α
c onc e ntrat ion by ELI SA m e t hod
using k it of Sur ve yor T M I C
H um a n/M ouse Tot a l H I F-1α
I m m unoa ssa y
Pa ra m e t e r on a lt e re d
c a rdia c m uscle c e ll
st ruc t ure :
hist opa thologic a l
ex a m ina tion of c a rdia c
m uscle by H & E st a ining
14
RESU LT
15
Pa ra m e t e r on hypox ia
Konsentrasi HIF-1 Alpha
Kelompok Aerobik dan Anaerobik
KURVA STANDAR HIF-1 ALPHA
250
y = 0,002x + 0,0759
R2 = 0,9989
1
0,8
Konsentrasi HIF-1 Alpa
s e ra p a n p a d a 4 5 0 n m
1,2
0,6
0,4
*
150
1 Hari
3 Hari
7 Hari
10 Hari
Aerobik
116,03
96,13
49,46
49,03
Anaerobik
156,8
55,5
54,96
52,5
Kontrol
100
200
300
400
500
KONSENTRASI HIF-1 ALPHA (pg/mL)
600
Δ
50
0
0
*
100
0,2
0
*
200
Kontrol
45,7
Kelompok
T he c onc e nt ra t ion of H I F-1 α in he a rt m usc le t issue
* Signific a nt diffe re nc e c om pa re w it h c ont rol group (p