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.

Sandra Gagnon

Study Director

As a study director, Sandra works routinely on pre-clinical models such as PAH and COPD. Over the past three years she and her team have developed the implantation method of pressure telemetry probes in rats.