There was also no significant difference in body weight and LV performance between the two groups. Table 1 Body weight and LV performance in doxorubicin treated and control rats Targeted ultrasound imaging Fig. 2 demonstrated the results of contrast echocardiography using A5MB. In rats treated with doxorubicin, the 1st frame showed significant contrast
opacification of myocardium; the signal coming from the adhered microbubbles (Fig. 2A). These retained microbubbles were destroyed during subsequent high mechanical index imaging. Therefore, no opacification was observed in the 10th frame (Fig. 2B). In control rats, unbound microbubbles dissipated during Inhibitors,research,lifescience,medical the waiting period and no contrast enhancement was observed in the 1st (Fig. 2C) or the 10th frames (Fig. 2D). Fig. Inhibitors,research,lifescience,medical 2 Targeted ultrasound imaging with annexin A5 conjugated microbubbles in doxorubicin-treated rats (A and B) and control rats (C and D). Significant contrast opacification of myocardium Inhibitors,research,lifescience,medical (arrows) was observed in the 1st frame (A). Initial contrast enhancement … TUNEL assay The result of the TUNEL assay revealed increased apoptosis frequencies for both the cardiomyocytes and endothelial cells of doxorubicin-treated hearts
compared to control hearts (Fig. 3). TUNEL-positive cardiomyocytes and endothelial cells Inhibitors,research,lifescience,medical were significantly higher in the doxorubicin-treated group than in the control group, which indicated that doxorubicin induced apoptosis of cardiomyocyte and endothelial cells (Fig. 4). Fig. 3 In situ labeling of DNA fragmentation in rat myocardium from TUNEL assay. Fragmented DNA is labeled in brown, and all nuclei
are counterstained with methyl-green. Myocardial sections from rats in the control group reveal no evidence of DNA fragmentation … Fig. 4 The quantitative results of positive TUNEL-staining cardiomyocytes and endothelial cells. The ratio of TUNEL-positive cardiomyocytes (A) and endothelial cells (B) Inhibitors,research,lifescience,medical are significantly higher in the doxorubicin-treated group (Doxo) than in the control group … Discussion The main finding of this study is that targeted ultrasound imaging using A5MB is capable of identifying apoptosis in acute doxorubicin induced cardiomyopathy. This study is the first description of an ultrasound approach for detecting apoptosis using a targeted because contrast agent and has major implications for noninvasive detection of early apoptosis in doxorubicin induced cardiomyopathy. In addition, it is AG-14361 molecular weight encouraging that apoptosis detection by ultrasound is possible in this study before definite LV systolic dysfunction occurs. Molecular imaging is a rapidly evolving discipline with the goal of developing tools to display and quantify molecular and cellular targets in vivo.