Effect of Calorie Restriction on Doxorubicin Induced Cardiac Dysfunction Celina Lucero Genysie Van Duren
Dec 27, 2015
Effect of Calorie Restriction on Doxorubicin Induced Cardiac
Dysfunction
Celina LuceroGenysie Van Duren
Potent Chemotherapy Effective against:
Solid tumors Leukemia breast cancer
Destroys cells by: Apoptosis DNA damage
Background: Doxorubicin (DOX)
Leukemia
DNA damage
Problem:
Attacks all metabolically active cells Damages cardiac tissue Creates reactive oxygen species and oxidative
stress Side Effects:
Cardiomyopathy Severe acute illnesses
“Red Death”
Background: DOX
Cardiac tissue
Form of dieting Proven to:
Extend lifespan Preserves cardiac function Lower body weight
Differing Effects: Acute= negative results Chronic= positive results
Background: Calorie Restriction (CR)
Used rats:
Split into 4 groups- Ad Lib (AL)+Saline (SAL), AL+DOX, CR+SAL, and
CR+DOX Done over 4 weeks Echocardiographs monitor heart:
M-mode= left ventricle Doppler= mitral and aortic valves
Introduction
Ekg: echocardiogram
Known facts:
DOX= effective…but dangerous CR= prolong heart functions
Combination? Both together= beneficial? Solve adverse effects of DOX Safer use with patients
Hypothesis/Purpose
Used Sprague-Dawley (Rattus norvegicus)
rats. Reliable and healthy subjects
Feeding: Normal first 2 weeks CR or AL treatments follow initial 2 weeks.
CR= 60% of AL intake
Methods
Methods
Timeline Instructions• At 10 wks animals (males and females) assigned to
feeding and activity regimens.• After a 2 week acclamation the DOX treatment will start• On weeks 2-9 the animals will receive either saline or
DOX at 2.5 mg/kg for a total dose of 20 mg/kg
Body Mass:
General decrease. CR= more No significant differences
M-mode: Variables generally the same Corrected velocity of circumferential shortening
(Vcfa) was only significant difference. Between CR+DOX and AL+DOX
Doppler: Variables generally the same No significant differences
Results
Baseline Week 1 Week 2 Week 3 Week 4 Week 5
AL+SAL
N/A 355 (0) 301 (81) 306.3 (76.4) 312.3 (87.9) 331.7 (73.5)
AL+DOX
325 (0) 305.3 (82.9) 306 (85.9) 301.8 (83.5) 312.3 (78) 306.5 (80.4)
CR+SAL
304.3 (68.8) 289 (59.9) 285.3 (65.4) 290 (65) 271.7 (62.5) 251 (61.5)
CR+DOX
337.5 (3.5) 310.5 (2.1) 308.5 (6.7) 326.5 (6.4) 274.5 (.7) 279.5 (.7)
Results
Table 1. Body Weight AveragesAverage body weights (g) over the course of the experiment. Number in parenthesis represent the standard deviation (StDev).
Results
FS
AL + SAL AL + DOX CR + SALCR + DOX0.000.050.100.150.200.250.300.350.400.450.500.550.600.65
Vcfa
AL + SAL AL + DOX CR + SALCR + DOX0.00000.00010.00020.00030.00040.00050.00060.00070.00080.00090.00100.0011
*
mm
/sec
Vcfa at week 4. Speed at which the percentage change from FS happens adjusted to heart size.
Fractional shortening at week 4. Percentage of wall change during diastole to systole.
Perc
en
tage
*The black portion of the graph represents the standard error.
Diastole= relaxationSystole= contraction
Body Mass:
CR= more weight loss DOX did not effect weight
DOX normally lowers weight M-mode:
Little thinning in LV walls Previous study= profound
thinning in LV walls Doppler:
No significant differences Fatalities:
Two rats in DOX group
Discussion
Top: M-mode Bottom: Doppler
Time Constraints:
Chronic CR proven to be better Rats did not have enough time.
Only 7.5 mg/kg of DOX injected cumulatively Previous studies= larger amount DOX Again longer period of time
Rats not exposed to DOX long enough
Subjects: Small sample size, decreased power
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