Serial Assessment of Myocardial Properties Using Cyclic Variation of Integrated Backscatter in an Adriamycin- Induced Cardiomyopathy Rat Model

Although adriamycin (Doxorubicin) is one of the most effective and useful antineoplastic agents for the treatment of a variety of malignancies, its repeated administration can induce irreversible myocardial damage and resultant heart failure. Currently, no marker to detect early cardiac damage is available. The purpose of this study was to investigate whether an assessment of the acoustic properties of the myocardium could enable the earlier detection of myocardial damage after adriamycin chemotherapy. Forty Wistar rats were treated with adriamycin (2 mg/kg, i.v.) once a week for 2, 4, 6 or 8 weeks consecutively. Left ventricular ejection fraction (LVEF) was calculated using M-mode echocardiography data. The magnitude of cardiac cycle dependent variation of integrated backscatter (CVIB) of the myocardium was measured in the mid segment of the septum and in the posterior wall of the left ventricle, using a real time two dimensional integrated backscatter imaging system. LVEF was significantly lower in the adriamycin-treated 8-week group than in the controls (75 +/- 9 vs 57 +/- 8%, p < 0.05). Myocyte damage was only seen in the 8-week adriamycin-treated group. However, no significant changes of CVIB were observed between baseline or during follow-up in the ADR or control group. In conclusion, serial assessment of the acoustic properties of the myocardium may not be an optimal tool for the early detection of myocardial damage after doxorubicin chemotherapy in a rat model.

The role of transesophageal three-dimensional echocardiography in the measurement of dynamic changes of atrial septal defect

No abstract available.

The Effect of Estrogen Containing Liposome Local Delivery on the Neointimal Hyperplasia in the Rat Carotid Artery Balloon-Injury Model

BACKGROUND AND OBJECTIVES: Estrogen has been reported to inhibit migration and proliferation of vascular smooth muscle cells in vitro and in vivo. Sustained local delivery represents a potential alternative to systemic administrationbecauseitcan achieve higher tissue drug levels at site of balloon injury avoiding systemic side effects. We investigated the effect and mechanism of nanoparticulate sustained-release carrier system using liposome incorporating 17beta-estradiol (E2) on neointimal formation in rat carotid artery balloon injury model. MATERIALS AND METHODS: 17-estradiol benzoate, egg phosphatidylcholine, cholesterol, polyethyleneglycol-phosphatidylethanolamine were mixed to produce E2 -liposome formula where the final concentrations of lipids and E2 were 10 mg/ml and 66 M, respectively. The size of the particle was less than 200 nm. Rat carotid artery balloon injury model was used with Sprague-Dawley rats weighing 350+/-30g. Rats were divided into 3 groups of saline (n=22), liposome (n=46) and E2-liposome (n=46) and received 0.2 ml of each agent at injured site. 1) Rats from all groups were sacrificed at 7 (n=4), 14 (n=6), and 21 (n=12) days after injury, respectively. Morphometric analysis was performed for calculating medial area, neointimal area and I/M (intimal area/medialarea)ratio2)Rats from liposome and E2-liposome group sreceived 100mg/kg of 5-bromo-2'-deoxyuridine (BrdU) at 25, 9 and 1hr before sacrifice at 1 (n=4), 3 (n=4), 7 (n=4), and 14 (n=4) days after injury. BrdU and proliferating cell nuclear antigen (PCNA) stains were performed to elucidate a mechanism of inhibitory effect of E2. RESULTS: 1) There was no increase in the neointimal area in liposome group compared with saline group at 7, 14, and 21 days after injury, respectively. 2) There was 17%, 30%, and 34% reduction of I/M ratio in E2 -liposome group compared with liposome group at 7, 14 and 21 days after injury, respectively. 3) BrdU and PCNA stain revealed that at day 3, labelling index (LI) of media was lower in E2-liposome than in liposome group (p<0.05), and at day 7, LI of neointima was not significantly different between the two groups despite smaller neointimal area in the E2-liposomegroup. CONCLUSION: Nanoparticulateliposomeformula appears to be biocompatible. Local intraluminal infusion of E2 liposome formula after balloon injury of rat carotid artery significantly decreased neointimal formation. The mechanism seems to be the inhibitory effect on the proliferative response of smooth muscle cells in media at an early stage of injury. This formula appears to show potential for clinical applications in the prevention of neointimal formation following balloon angioplsty.