Identifying early stages of doxorubicin-induced cardiotoxicity in rat model by 7.0 tesla cardiovascular magnetic resonance combining hematological and pathological parameters.

PURPOSE

To identify early doxorubicin-induced cardiotoxicity by applying 7.0 T cardiac magnetic resonance (CMR) combined with creatine kinase isoenzymes (CKMB) from rat models, using pathological results as a reference standard.

METHODS

The 48 male rats included in the study were divided into a doxorubicin (DOX) group (n = 32) and a control group (n = 16). Each group was further divided into four subgroups according to the interval weeks between the first administration and CMR examination. DOX group and the controls were injected with DOX (2.5 mg/kg) or physiological saline (2.5 mg/kg) through vena caudalis weekly. The rats in first subgroup received 4 weekly injections and were sacrificed after CMR examination at week 4. Rats in the second, third and fourth DOX or control subgroups underwent 6 weekly injections and were sacrificed after CMR examination at weeks 6, 8 and 10, respectively. The conventional cardiac function parameters, myocardial strain, standardized myocardial T2 value, late gadolinium enhancement, CKMB and pathological results of each rat were analyzed.

RESULTS

The LV mass index was reduced and CKMB was increased in the first subgroup (week 4), global circumference strain was decreased and normalized myocardial T2 relaxation time was prolonged in the second subgroup (week 6). At these early point of time, LVEF remained unaffected. Myocardial fibrosis was observed in the third and fourth subgroups (in week 8 and 10, respectively) and the collagen volume fraction was significantly negatively correlated with the LVEF and myocardial strain.

CONCLUSIONS

CMR can be used to identify doxorubicin-induced cardiotoxicity at early stage, with the LV mass index, global circumference strain, normalized myocardial T2 relaxation time as the early markers. CKMB can indicate the optimal timing for CMR examination of chemotherapy recipients to improve medical efficiency. Myocardial fibrosis persists in the advanced stage of doxorubicin-induced cardiotoxicity which comprises the main cause of LV dysfunction.