Coronary Blood Flow is Reduced by Doxorubicin: a Ultrasound Microscopic Study

Abstract

The use of doxorubicin (DOX), an anti‐cancer drug, in treatment for various malignancies is limited because of its cardiotoxicity; whether DOX causes vascular disorders is unknown. Ultrasound biomicroscopy (UBM) has been a valuable, non‐invasive technique in monitoring cardiac function but not commonly used in small animal vascular studies.This study aimed to 1) study the velocity of blood flow in the left coronary artery (LCA) under physiological conditions and vascular responsiveness to DOX treatment with UBM, and 2) examine the effect of an aqueous extract of TA bark (TAAqE), a cardiotonic, on the blood‐flow velocity of LCA after DOX treatment. Young adult mice were injected intrapleurally with a single dose of DOX (20 mg/kg) or saline in the presence or absence of TAAqE. Doppler UBM was performed the day before and 1 week after DOX treatment using Vevo®2100. The blood flow of LCA and left ventricle (LV) function were monitored in the parasternal short‐axis view of UBM. The peak blood‐flow velocity of LCA during cardiac diastole and systole was 909±35 and 284±13 mm/s, respectively, (n=20) without drug treatment. Abnormality of LV function could be detected in the 1st week and was increased rapidly in the 2nd week of DOX treatment. Meanwhile, the integrated blood flow of LCA was reduced about 42% (n=9) accompanied by an increase in the resistive index by 85%. Pretreatment of TAAqE offset the detrimental effects of DOX on LCA and LV function. In summary, 1) DOX caused reduction in LCA blood‐flow velocity besides cardiotoxicity, and 2) TAAqE offered some cardiovascular protective effects. In conclusion, Doppler UBM is very useful in detecting longitudinal hemodynamic changes of LCA. The DOX‐induced decrease in blood‐flow velocity of LCA could result from reduction in the blood flow and/or vasoconstriction.