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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased oxidative stress and antioxidant deficit have been suggested to play a major role in adriamycin-induced cardiomyopathy and congestive heart failure due to multiple treatments with adriamycin (doxorubicin). In this study, we investigated the acute effects of a single dose of adriamycin on myocardial antioxidant enzymes in rats. Adriamycin (2.5 mg/kg) was injected (i.p.) and myocardial antioxidant enzyme activities, mRNA abundance and protein levels at 1, 2, 4 and 24 h were examined. While manganese superoxide dismutase (MnSOD), glutathione peroxidase (GSHPx) and catalase (CAT) activities were not significantly changed, copper-zinc superoxide dismutase (CuZnSOD) activity was reduced at all time points and this change correlated with a decrease in its protein content. CuZnSOD mRNA was increased at 1 and 24 h. GSHPx mRNA and protein levels were transiently decreased by 20 and 25% respectively at 2 h. MnSOD mRNA was not significantly changed, but its protein levels were significantly decreased at 1 h. Lipid peroxidation was increased transiently at 1, 2 and 4 h. A transient depression in antioxidant enzyme as well as transient increase in oxidative stress with a single dose of adriamycin may precede more sustained changes seen with the repeated administration of the drug and contribute to the development of cardiomyopathy and heart failure.
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PMID:Early changes in myocardial antioxidant enzymes in rats treated with adriamycin. 1203 Mar 76

This article provides a comprehensive review of 30 years of research on the use of coenzyme Q10 in prevention and treatment of cardiovascular disease. This endogenous antioxidant has potential for use in prevention and treatment of cardiovascular disease, particularly hypertension, hyperlipidemia, coronary artery disease, and heart failure. It appears that levels of coenzyme Q10 are decreased during therapy with HMG-CoA reductase inhibitors, gemfibrozil, Adriamycin, and certain beta blockers. Further clinical trials are warranted, but because of its low toxicity it may be appropriate to recommend coenzyme Q10 to select patients as an adjunct to conventional treatment.
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PMID:Coenzyme Q10 and cardiovascular disease: a review. 1259 59

Doxorubicin (Adriamycin) is a potent and broad-spectrum antineoplastic agent prescribed for the treatment of a variety of cancers, including both solid tumours and leukaemias. Unfortunately, despite its broad effectiveness, long-term therapy with doxorubicin is associated with a high incidence of a cumulative and irreversible dilated cardiomyopathy. Numerous mechanisms have been proposed to account for this toxicity. Although there is general consensus that doxorubicin undergoes redox cycling to generate free radicals that are responsible for mediating the various cytopathologies associated with drug exposure, the source and subcellular targets continue to be debated. This short review provides a synopsis of the evidence implicating cardiac mitochondria as key intracellular targets, both as sites of generation of highly reactive free radical intermediates as well as targets for the interference with cell calcium regulation and bioenergetic failure that are hallmarks of doxorubicin-induced cardiac failure.
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PMID:Doxorubicin-induced cardiac mitochondrionopathy. 1296 34

Doxorubicin (DXR) is one of the most effective antineoplastic agents, but its use is limited by its myocardial toxicity. Myocardial injury reduces the cyclic variation of integrated backscatter (CV-IBS) and so the present study was designed to investigate whether CV-IBS can be used to detect the early phase of myocardial damage in patients receiving DXR. Thirty-four subjects constituted the study population, none of whom showed clinically evident heart failure. CV-IBS was obtained for both the interventricular septum and the left ventricular posterior wall in the parasternal short-axis view. Standard echographic measures of left ventricular function were also made. Subjects without DXR exposure or evident cardiac diseases served as controls. The total dose of DXR administered per patient was 339+/-164 mg/m2 (range: 95-680 mg/m2). Conventional echographic parameters, including left ventricular wall thickness, dimensions, fractional shortening, and ejection fraction, showed no significant differences between the 2 groups. In contrast, CV-IBS was significantly decreased in the DXR group compared with the control group (septum: 4.7+/-1.7 vs 7.2+/-1.9 dB, p<0.0001; posterior wall: 6.7 +/-2.2 vs 8.0+/-1.6 dB, p<0.05). CV-IBS can be used as an early indicator of DXR-induced myocardial damage in patients demonstrating normal left ventricular systolic function.
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PMID:Early detection of doxorubicin-induced myocardial damage by ultrasound tissue characterization with integrated backscatter. 1457 99

Doxorubicin is an anti-tumor agent that represses cardiac-specific gene expression and induces myocardial cell apoptosis. Doxorubicin depletes cardiac p300, a transcriptional coactivator that is required for the maintenance of the differentiated phenotype of cardiac myocytes. However, the role of p300 in protection against doxorubicin-induced apoptosis is unknown. Transgenic mice overexpressing p300 in the heart and wild-type mice were subjected to doxorubicin treatment. Compared with wild-type mice, transgenic mice exhibited higher survival rate as well as more preserved left ventricular function and cardiac expression of alpha-sarcomeric actin. Doxorubicin induced myocardial cell apoptosis in wild-type mice but not in transgenic mice. Expression of p300 increased the cardiac level of bcl-2 and mdm-2, but not that of p53 or other members of the bcl-2 family. These findings demonstrate that overexpression of p300 protects cardiac myocytes from doxorubicin-induced apoptosis and reduces the extent of acute heart failure in adult mice in vivo.
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PMID:Expression of p300 protects cardiac myocytes from apoptosis in vivo. 1497 62

Heart failure due to a variety of causes is accompanied by an upregulation of cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). Adriamycin-induced cardiomyopathy (AIC) and heart failure is an important clinical problem. The current study investigated the expression of these cytokines in AIC and heart failure in rats. Both early and late stages of AIC was produced in rats. Myocardial gene expressions for TNF-alpha, IL-1beta and IL-6 were examined with DNA microarrays and RT-PCR. Protein levels of these cytokines in both the plasma and the myocardium were also examined by ELISA. In the early stage, myocardial mRNA expression of IL-1beta showed significant increase at 4 and 24 h, peaking at 4 h, while TNF-alpha did not change and IL-6 was undetectable. The protein levels of these three genes did not show any upregulation in the plasma or the heart. In the late stage, heart failure was confirmed by clinical signs as well as homodynamic changes. In this stage, plasma protein levels for TNF-alpha, IL-1beta and IL-6 were not changed. However, myocardial TNF-alpha mRNA expression and protein levels were significantly decreased, while both IL-1beta mRNA and protein levels were not different compared to the control group. IL-6 mRNA expression was undetectable in both normal and adriamycin-treated hearts while its protein level was not changed by adriamycin. Positive control using lipopolysaccharides (LPS) treatment (0.5 mg/kg body weight) for 2 h resulted in a significant increase in these three cytokines in the heart and plasma. These data suggest that an upregulation of cytokines may not be involved in AIC. Heart failure may in fact be accentuated by a downregulation of myocardial TNF-alpha.
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PMID:Cytokines are not upregulated in adriamycin-induced cardiomyopathy and heart failure. 1513 63

Doxorubicin is a chemotherapeutic agent successfully used in the treatment of a wide range of cancers. However, with cumulative doses, doxorubicin also is known to have cardiotoxic effects, including cardiomyopathy and heart failure. Research is targeted at maximizing the antitumor effects of doxorubicin while attenuating the potential cardiotoxicity. Concurrent therapies under study are combinations of doxorubicin with drugs such as probucol, carvedilol (Coreg, GlaxoSmithKline, Research Triangle Park, NC), dexrazoxane (Zinecard, Pfizer, New York, NY), and antioxidant nutrients. As patient advocates, nurses must be aware of current research, treatment options, and evidence-based patient resources and be diligent in assessing and educating patients before, during, and after treatment with doxorubicin.
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PMID:Concurrent therapies that protect against doxorubicin-induced cardiomyopathy. 1551 83

Doxorubicin is a commonly used cytotoxic drug for effective treatment of both solid tumors and leukemias, which may cause severe cardiac adverse effects leading to heart failure. In certain tumor cells, doxorubicin-induced cell death is mediated by death receptors such as CD95/Apo-1/Fas. Here we studied the role of death receptors for doxorubicin-induced cell death in primary neonatal rat cardiomyocytes and the embryonic cardiomyocytic cell line H9c2.1. Doxorubicin-induced cell death of cardiomyocytes was associated with cleavage of caspases 3 and 8, a drop in mitochondrial transmembrane potential, and release of cytochrome c. Doxorubicin-treated cardiomyocytes secreted death-inducing ligands into the culture supernatant, but remained resistant toward cell death induction by death receptor triggering. In contrast to the chelator dexrazoxane, blockade of death receptor signaling by stable overexpression of transdominant negative adapter molecule FADD did not inhibit doxorubicin-induced cell death. Our data suggest that cultured cardiomyocytes secrete death-inducing ligands, but undergo death receptor-independent cell death upon exposure to doxorubicin.
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PMID:CD95/Apo-1/Fas: independent cell death induced by doxorubicin in normal cultured cardiomyocytes. 1570 61

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.
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PMID:Serial assessment of myocardial properties using cyclic variation of integrated backscatter in an adriamycin-induced cardiomyopathy rat model. 1574 8

Doxorubicin-induced cardiomyopathy is not uncommon and may progress to end-stage heart failure. Treatment of this condition with heart transplantation, however, requires that the primary malignancy be deemed "cured." We present the case of a 55- year-old woman who had doxorubicin-induced cardiomyopathy and non-Hodgkin's lymphoma. The active status of her lymphoma precluded heart transplantation. She had end-stage heart failure and underwent the insertion of a left ventricular assist device as a destination therapy.
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PMID:Left ventricular assist device as destination therapy in doxorubicin-induced cardiomyopathy. 1603 40


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