QF1-008 - Evaluation of diffuse myocardial characteristics based on daunorubicin-induced cardiotoxicity by CMR: an animal study

Background: The cardiotoxicity is one of the most common adverse effect for the anthracyclines therapy. Daunorubicin (DNR) serve as the backbone of many anti-cancer treatment strategies, but DNR-induced cardiotoxicity was rarely reported compared with doxorubicin (DOX).

Methods: Thirty-eight adult male New Zealand white rabbits weighing 2 to 4 kg were included in this study. There were three groups including control subjects with sterile saline, the DNR subjects with 3 or 4 mg/kg respectively. The CMR imaging including the function, native T1 mapping and LGE. The myocardial enzyme was analyzed. The time points were 2 weeks and 4 weeks, and according to the cumulative dose, all modeling subjects were divided into mild, moderate and severe groups. Some subjects were sacrificed for histological evaluation at the end of CMR scan.

Results: In the group of controls rabbits and DNR rabbits, the EF were decreased from 2 weeks to 4 weeks (controls 62.32±7.95% vs. 2 weeks 56.29±5.64% vs. 4 weeks 52.41±11.35%). We also divided all modeling rabbits into three groups by the different cumulative dose. The EF in high dose group had lower than the controls. For the T1 mapping analysis, the global native T1 values in rabbits with 4mg/kg weekly at 2 and 4 weeks were significantly higher than the controls (P < 0.05). All modeling rabbit had higher T1 values than controls the high dose group had higher T1 values than moderate dose group. Most of the DNR rabbits (94.68%) were without the presence of LGE, only a few of subjects (5.32%) showed the LGE positive in subendocardial or the free wall. The Masson stain showed diffuse extracellular collagen deposition in the LV myocardium between mild, middle and high dose groups.

Conclusion: Native T1 mapping could detect diffuse myocardial injury in 4 weeks cause by daunorubicin. The higher cumulative dose and longer time may have more severe myocardium injury.