Nonclinical Models of Heart Failure - Doxorubicin Cardiomyopathy
1.
2. ANIMAL MODEL OF HF: TOXIC CARDIOMYOPATHY
Strain: C57BL/6NCrl mice (male)
Body weight: 23 to 28 g
Doxorubicin (Sigma; concentration 7.5 mg/mL; dose volume 2 mL/kg)
Echocardiography: Study Day 5 (Vevo 2100)
Systolic Function: PSAX M-mode
Morphology: PSAX M-mode
Diastolic Function: PW Doppler of the mitral valve flow and Tissue Doppler of the mitral valve annulus
Weight of the Heart and Lungs: Cardiac Hypertrophy
Circulating Biomarkers: Creatine Kinase
Group 1: Vehicle (saline 2 mL/kg)
Group 2: Doxorubicin (15 mg/kg)
3. Hullin R et al Cardiovasc Res 2018 1;114(2):272-281
Acute DOX Model
C57BL/6J mice received a single intraperitoneal (i.p.)
injection of Dox–HCl at 15 mg/kg. Echocardiographic
measurements were obtained 5 days after injection.
Mouse Model of Doxorubicin-Induced Heart Failure
Survival rate at 8 days post DOX ≈55% 0 1 2 3 4 5 6
0
5 0
1 0 0
S u rv iv a l C u rv e
D a y s
S
u
r
v
iv
a
l
(
%
)
V e h ic le (n = 7 )
D o x o ru b ic in (n = 1 3 )
1 0 0 %
Each value represents mean ± SD
*p < .05 vs Vehicle (unpaired sample t-test)
4. Mouse Model of Doxorubicin-Induced Heart Failure
Hullin R et al Cardiovasc Res 2018 1;114(2):272-281
Acute DOX Model
Each value represents mean ± SD
*p < .05 vs Vehicle (unpaired sample t-test)
3% change
from Vehicle
5. Mouse Model of Doxorubicin-Induced Heart Failure
Morphological Changes
Each value represents mean ± SD
*p < .05 vs Vehicle (unpaired sample t-test)
LVPWED: left ventricle posterior wall at end diastole
LVPWES: left ventricle posterior wall at end systole
LVEDD: left ventricle end diastolic diameter
LVESD: left ventricle end systolic diameter
HR: heart rate
Hullin R et al Cardiovasc Res 2018 1;114(2):272-281
Acute DOX Model
6. Mouse Model of Doxorubicin-Induced Heart Failure
Each value represents mean ± SD
*p < .05 vs Vehicle (unpaired sample t-test)
Hullin R et al Cardiovasc Res
2018 1;114(2):272-281
Acute DOX Model
7. Mouse Model of Doxorubicin-Induced Heart Failure
Each value represents mean ± SD
*p < .05 vs Vehicle (unpaired sample t-test)
8. Mouse Model of Doxorubicin-Induced Heart Failure
Diastolic Function
E’: Early diastolic velocity, reflects
relaxation of the myocardium
E/E’ (LV Filling Pressure Estimation):
Ratio between early mitral inflow
velocity and mitral annular early
diastolic velocity. Left ventricular
diastolic dysfunction index.
Each value represents mean ± SD
*p < .05 vs Vehicle (unpaired sample t-test)
Hullin R et al Cardiovasc Res 2018 1;114(2):272-281
Acute DOX Model
9. Mouse Model of Doxorubicin-Induced Heart Failure
Circulating Levels of Creatine Kinase (CK) at Day 5
Each value represents mean ± SD
*p < .05 vs Vehicle (unpaired sample t-test)