This study attempted to assess the incidence and outcome of anthracycline cardiotoxicity and the role of dexrazoxane as a cardioprotectant in childhood solid tumors. The dexrazoxane group included 47 patients and the control group of historical cohort included 42. Dexrazoxane was given in the 10:1 ratio to doxorubicin. Fractional shortening and systolic and diastolic left ventricular diameters were used to assess the cardiac function. The median follow-ups were 54 months in the dexrazoxane group and 86 months in the control group. The mean cumulative doses of doxorubicin were 280.8+/-83.4 mg/m2 in the dexrazoxane group and 266.1+/-75.0 mg/m2 in the control group. The dexrazoxane group experienced significantly fewer cardiac events (27.7% vs. 52.4%) and less severe congestive heart failure (6.4% vs. 14.3%) than the control group. Thirteen cardiotoxicities including one cardiac death and 2 congestive heart failures occurred in the dexrazoxane group, and 22 cardiotoxicities including 2 cardiac deaths and 4 congestive heart failures, in the control group. Five year cardiac event free survival rates were 69.2% in the dexrazoxane group and 45.8% in the control group (P=0.04). Dexrazoxane reduces the incidence and severity of early and late anthracycline cardiotoxicity in childhood solid tumors.
Adolescent ; Antibiotics, Antineoplastic/*adverse effects ; Cardiomyopathies/chemically induced/prevention & control ; Cardiovascular Agents/*therapeutic use ; Child ; Child, Preschool ; Cohort Studies ; Disease-Free Survival ; Doxorubicin/*adverse effects ; Echocardiography ; Female ; Follow-Up Studies ; Heart Failure/chemically induced/prevention & control ; Humans ; Infant ; Male ; Neoplasms/*drug therapy/mortality ; Razoxane/*therapeutic use ; Ventricular Function, Left/physiology

AIMTo investigate the effects of hepatocyte growth factor gene transfected MSCs transplantation on cardiac function and fibrosis in rats heart failure model induced by adriamycin.

METHODSMSCs were isolated from SD rats by density gradient centrifugation, purified, and transfected with Ad-hHGF. ELISA were used to detect the protein expression of hHGF in these MSCs. Forty SD rats underwent intraperitoneal injection with adriamycin to induce heart failure model. 8 healthy rats served as control, 24 survival rats were randomly divided into 3 groups (n = 8): Rats in Ad-hHGF transfected MSCs group were injected with Ad-hHGF transfected MSCs 2 weeks after the establishment of the model, rats in MSC group injected with suspension of MSCs only, and model group was injected with cold culture fluid. Heart function was evaluated by a physiological recorder 4 weeks after cell transplantation. Myocardial cell morphology and interstitial collagen were studied by electron microscope and were stained by Sirus red. TGF-beta1 was detected by immunohistochemical method.

RESULTS(1) MSCs could be transfected efficiently by Ad-hHGF, manifested by a higher level of expression in vitro, persisting 14 days at least. (2) Four weeks after the cells transplantion, cardiac necrosis in MSC-hHGF rats was improved when compared with those in the MSCs (P < 0.05) and Model group (P < 0.01). The heart function of the MSC-hHGF rats was greatly improved with an significant increase in LVSP and + dp/dt(max), although LVEDP still highter than that of normal rats. (3) MSC-Ad-hHGF decreased Myocardial collagen content and the level of TGFbeta1 compaired with MSCs transplanted rats (P < 0.01).

CONCLUSIONTransplantation of HGF gene transfected MSCs improved heart function, decreased myocardial collagen and the level of TGFbeta1.

Animals ; Doxorubicin ; Fibrosis ; metabolism ; prevention & control ; Heart Failure ; chemically induced ; physiopathology ; therapy ; Hepatocyte Growth Factor ; genetics ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; metabolism ; Myocardium ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transfection

OBJECTIVETo study the effects and mechanism of Buzhong Yiqi decoction on adriamycin-induced acute myocardial injury in rats.

METHOD50 rats were randomly divided to five groups: control group, heart failure group, low dose Buzhong Yiqi decoction, high dose Buzhong Yiqi decoction and captopril group. Adriamycin was injected into the latter four groups to built a model of heart failure. Then, the effects of different doses of Buzhong Yiqi decoction on hemodynamics, cardiac tissue histological changes, antioxidant capacity and apoptosis of the damaged hearts were studied.

RESULTAdriamycin led to myocardial fiber swelling and fracture, Buzhong Yiqi decoction could reduce myocardial lesions. Buzhong Yiqi decoction could also improve heart antioxidant capacity and inhibit adriamycin-induced cardiomyocyte apoptosis.

CONCLUSIONBuzhong Yiqi decoction could significantly ease adriamycin induced heart failure in rats, and the mechanism is related to anti-oxidation and inhibiting apoptosis.

Animals ; Antibiotics, Antineoplastic ; toxicity ; Doxorubicin ; toxicity ; Drugs, Chinese Herbal ; pharmacology ; Heart Failure ; chemically induced ; prevention & control ; Male ; Nitric Oxide ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood ; Ventricular Function, Left ; drug effects

OBJECTIVETo study the treatment effect of Wenxin Keli on isoproterenol (ISO) induced heart failure in rats.

METHODSixty six-week old male Wistar rats were randomized into six groups. The rats in control group were only receive distilled water every day. The rats in ISO group also received two subcutaneous injections (85 mg x kg(-1)) of ISO, which were separated by a 24 hour interval and began to receive distilled water 2 weeks later every day. The rats in Wenxin Keli and control group were receive Wenxin Keli (9 mg x kg(-1)) every day. The rats in Wenxin Keli and ISO group received two subcutaneous injections (85 mg x kg(-1)) of ISO, which were separated by a 24 hour interval and began to receive Wenxin Keli (9 mg x kg(-1)) 2 weeks later every day. The rats in valsartan and control group were receive valsartan every day. The rats in valsartan and ISO group received two subcutaneous injections (85 mg x kg(-1)) of ISO, which were separated by a 24 hour interval and began to receive valsartan 30 mg x kg(-1) 2 weeks later every day. Echocardiogram measurement in rats were carried out after 4 weeks and 10 weeks feeding medince of hemodynamic measurement and aconitine induced arrhythmia in rats were carried out after 10 weeks.

RESULTEchocardiogram indicated that left ventricular internal diameter at diastolic phase (LVIDd), left ventricular internal diameter at systolic phase (LVIDs), LV percent fractional shortening (FS) and LV ejection fraction (EF) were decreased in the ISO group. Treatment with valsartan 4 weeks later, FS and EF were increased compared with the ISO group and 10 weeks later, LVIDd, LVIDs, FS, EF were increased. However, treatment with Wenxin Keli 10 weeks later, LVIDs, FS, EF were not changed obviously. Hemodynamic measurement showed that left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), and dp/dt(max) were improved after 10 weeks of treatment with valsartan. The LVEDP was decreased and dp/dt(max), was increased after 10 weeks of treatment with Wenxin Keli. Aconitine induced arrhythmia in rats in Wenxin Keli and control group were less serious than those in control group, aconitine induced arrhythmia in rats in Wenxin Keli and ISO group were less serious than those in ISO group.

CONCLUSIONWenxin Keli could greatly improve the ISO induced cardiac dysfunction and protect the aconitine-induced arrhythmia in rats.

Animals ; Arrhythmias, Cardiac ; diagnostic imaging ; physiopathology ; prevention & control ; Cardiotonic Agents ; isolation & purification ; pharmacology ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Echocardiography ; Heart ; drug effects ; physiopathology ; Heart Failure ; chemically induced ; physiopathology ; prevention & control ; Hemodynamics ; drug effects ; Isoproterenol ; Male ; Myocardium ; pathology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Ventricular Function, Left ; drug effects