Heart failure model: Anthracyclin toxicity
Purpose
Heart failure results from classical myocardial toxicity + DNA damage without repairs.
Loss of myocardial filament organization.
Decreased cardiac output associated with ↘ ejection fraction, ↘ fractional shortening, ↘ everything.
Detectable within 72 hours post injection #1
Severe, irreversible, essentially a survival model.
Method
Intraperitoneal injection of 2 mg/kg doxorubicin every 2 days for 7 days
Cumulative dose of doxorubicin determines the extent of the damage
Study outcome
Cardiac echography (ultrasound)
Invasive hemodynamics (BP, HR, P-V loop, ECG)
Biomarkers (troponins, CKMB, ANP, NT-Pro-BNP)
Histology
Major limitations
Extremely variable from one animal to the next
Irreversible: efficacy means a mitigation of damage, right-shift in doses of anthracyclin which can be used before toxicity becomes crippling.