Narine Sarvazyan, Ph.D. Pharmacology and Physiology Dept, The George Washington University Medical...
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Transcript of Narine Sarvazyan, Ph.D. Pharmacology and Physiology Dept, The George Washington University Medical...
Narine Sarvazyan, Ph.D.Pharmacology and Physiology Dept, The George Washington University Medical Center
Arrhythmias
Wave PROPAGATION disturbances
Normal rhythm Reentry
inlet 1 inlet 2 outlet
stainless
steel holder
coverslip
inlet 1
inlet 2
outlet
A. CROSS SECTION
B. BOTTOM VIEW
I - Zone
Peltier-
controllered
mount
Plastic
holder
* *
25 mm
pacing electrodes
+ =cells
chamber
Time (sec)210 215 220 225 230 235
80
100
120
140
A.U
.F. (F
luo-4
)
D
A200 m
218.554 218.773 219.100
control zone
I-zone
B
C
0
660
msec
200 m
* * ** * *
200 m
Time (sec)210 215 220 225 230 235
80
100
120
140
A.U
.F. (F
luo-4
)
D
A200 m
218.554 218.773 219.100
control zone
I-zone
B
C
0
660
msec
200 m
* * ** * *
200 m
I. Cellular Origins of Ectopic Arrhythmias
Ectopic
Wave INITIATION disturbances
Time/sec550 600 650
A.U
.F. (
Flu
o-4
) A
B
80
100
120
140
575 625
I-zone
controlzone
C
2
4
6
8
[Ca
++],
nM
/s
P < 0.01
*
200 m
In silico
In vitro
I
IIIV
I - synchronized activity II - propagationIII - propagation failureIV - individual ectopicsV - local ectopic wavesVI - spreading ectopic waves
V
Ectopic excitability
Cell-to-cell coupling highlow
highlow
VI
transition curve
III
0.00
0.04
0.08
0.12
0.16
Diffusion coefficient, Dx10-4 ( cm2/s)
<
>
1 2 3 4 50
BOUNDARY ACTIVITY in 3D: computer simulations
Micro-reentriesEctopic beats
II. Stems cells & cardiac regeneration
A B
C D
Contracting cells of cardiac lineage are fluorescent within attached embryoid body. Phase-contrast picture of attached embryoid body and its fluorescent image.
embryoid body α-MHC-GFPconstruct
III. Cardiotoxicity of anthracyclines
Doxo
rubicin
,
040
80120
160
Mean fluorescence intensity
0 25 50
Myocytes load
ed w
ith D
FDA
Control m
yocytes
515530
610
Wavele
ngth
, n
m
500
550
600
650
DIC
HLO
RO
FLU
OR
ESC
EIN
AD
RIA
MYC
INC
H1
CH
2C
hannel 1
AD
BCC
hannel 2
Adria
mycin
,
040
80
120
160
0 25
50
Myocyte
s lo
aded w
ith D
CFH
Contro
l myocyte
s
DCF intensity
phospholipidsphospholipid
hydroperoxides oxidized fatty acids
DOX
ROS PLA2
_+
GPX/GSH,otherantioxidants
HPGPX
Reduction of oxidized fatty acids/lysophospholipids,and membrane remodeling
+ +
+
+_
promote
inhibit
phospholipidsphospholipid
hydroperoxides oxidized fatty acids
DOX
ROS PLA2
_+
GPX/GSH,otherantioxidants
HPGPX
Reduction of oxidized fatty acids/lysophospholipids,and membrane remodeling
+ +
+
+_
promote
inhibit
Acknowledgement of financial support: NIH and American Heart Association
Other areas of interest:
doxorubicin induced oxidative stress
Phospholipase A2 inhibition