Doxorubicin (DOX)-Induced Cardiomyopathy Model

Model Description

Doxorubicin, a widely used anthracycline chemotherapeutic agent, induces dose-dependent cardiotoxicity through mechanisms including oxidative stress, mitochondrial dysfunction, and topoisomerase IIβ inhibition. Our model replicates key clinical manifestations:

• Chronic heart failure progression: LVEF reduction ≤40% at 2 week
• Arrhythmogenic susceptibility: Premature ventricular contractions (PVCs >50/24h)
• Histopathological hallmarks: Myocyte vacuolization, interstitial fibrosis (≥20% collagen deposition)

Key Advantages:
✓ High translational fidelity: 92% genomic overlap with human cardiotoxicity pathways
✓ Controlled toxicity: Standardized 2-week induction protocol
✓ Multi-parametric validation: Functional, molecular, and structural endpoints

Applications

• Cardioprotective drug screening (dexrazoxane analogs, ROS scavengers)
• Chemotherapy adjuvant therapy development
• Cardiac remodeling mechanism studies
• Biomarker discovery (troponin I, NT-proBNP kinetics)

Modeling Protocol —— Doxorubicin Induction Workflow

1. Dosing Regimen:

• Intraperitoneal injection: 7.5 mg/kg DOX (6 doses, Q3D)
• Control group: Equivalent saline volume

2. Monitoring:

• Weekly body weight tracking (humane endpoint: >15% loss)
• ECG telemetry (lead II) for arrhythmia detection

Validation & Testing