Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Doxorubicin (Adriamycin), a potent antineoplastic drug, produces progressive cardiotoxicity which may lead to ultimate cardiac failure. The effects of chronic doxorubicin treatment on cardiac actomyosin ATPase were the principal focus of the present studies. This approach was based on the established correlation between cardiac contractility and contractile protein ATPase activity. Rabbits were injected intravenously with doxorubicin (4 mg/kg) at weekly intervals for 1-7 weeks. Body weight increase was attenuated in the treated animals; heart weight/body weight ratio was unchanged. Actomyosin and water contents of ventricular muscle were not different in doxorubicin-treated as compared with vehicle control animals. Cellular damage was detected histologically after one dose of doxorubicin (equivalent to a single clinical dose), and was extensive after 4-5 weeks of treatment. Animals which received 1-2 injections of doxorubicin demonstrated a 29% average increase in actomyosin ATPase activity as compared to vehicle controls; this difference was highly significant (p less than 0.001). Further treatment with doxorubicin tended to progressively decrease ATPase activity. It is suggested that the increased actomyosin ATPase activity seen with low total doses of doxorubicin may represent a compensatory mechanism for maintenance of contractility; this interpretation is supported by the clinical observation that the morphologic evidence of progressive doxorubicin toxicity is not associated with a parallel decrease in contractility, until severe cumulative toxicity has been induced.
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PMID:Cardiac actomyosin ATPase activity after chronic doxorubicin treatment. 315 43

(2'' R)-4'-O-Tetrahydropyranyl Adriamycin (THP) is a new antitumor agent discovered among series of similar anthracycline compound synthesized by Umezawa et al. Phase I study revealed dose limiting factor of leukopenia with upper GI toxicity. Alopecia, cardiac failure and transient hepatic failure were extremely mild. Definite responses were demonstrated in acute leukemia, lymphoma, ovarian carcinoma, head and neck carcinoma, breast carcinoma and GU carcinoma. Pharmacokinetic studies revealed rapid cell uptake and outputs in bile (20%) and urine (8%) in 24 hours. Transfer to third spaces were poor but definite. In vivo a part of THP was converted to ADM in the liver, but not in other tissues including tumors. THP would be an extremely interesting compound, because of comparable spectrum of responses to various tumors with extremely low toxicity compared with other anthracycline compounds.
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PMID:Clinical studies of (2''R)-4'-O-tetrahydropyranyl adriamycin (THP). 331 Nov 90

Present noninvasive techniques to detect Adriamycin (doxorubicin) cardiotoxicity rely on assessment of myocardial function rather than direct observation of change in tissue character. Proton nuclear magnetic resonance imaging may provide a unique means of characterizing the myocardium. The relaxation properties T1 and T2 are related to certain biophysical properties of tissue such as water, lipid, and macromolecular content and have considerable impact on the intensity observed in nuclear magnetic resonance images. In a model of chronic Adriamycin cardiotoxicity in rats, T1 values of excised hearts were elevated, relative to control, in rats with histologic evidence of chronic cardiotoxicity (651 msec vs 622 msec, p less than 0.05) and more so in rats with gross evidence of toxicity or heart failure (668 msec, p less than 0.005). No significant change in T2 was observed. This T1 prolongation increases as disease worsens, whereas water concentration did not change significantly. The results suggest that predictable prolongation in T1 occurs in association with cardiotoxicity. In conclusion, proton nuclear magnetic resonance imaging methods could provide a new means for assessing Adriamycin cardiotoxicity.
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PMID:Adriamycin cardiotoxicity and proton nuclear magnetic resonance relaxation properties. 359 13

One-hundred-fourteen evaluable patients with metastatic soft tissue or bony sarcoma with measurable disease were treated with Adriamycin (doxorubicin) administered intravenously at a dose of 60 mg/M2 on day 1, followed by DTIC (dacarbazine) at a dose of 750 mg/M2; courses were administered at 3-week intervals. Ten complete remissions and 17 partial remissions were observed. The most responsive cell type was malignant fibrous histiocytoma with a response rate of 54%. This treatment schedule was very well tolerated, with only moderate myelosuppression and moderate nausea and vomiting. Cardiac toxicity was identified in three patients, with two patients demonstrating electrocardiogram (EKG) changes and arrhythmias and only one patient developing heart failure. The 24% overall response rate suggests no compromise in activity on this schedule, with a significant reduction in toxicity.
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PMID:A useful high-dose intermittent schedule of adriamycin and DTIC in the treatment of advanced sarcomas. 375 66

Adriamycin (doxorubicin), one of the most active cytotoxic antineoplastic agents, can cause heart failure. This side effect is dose-dependent, the frequency of heart failure being 3% at a cumulative Adriamycin dose of 400 mg/m2 and 18% at 700 mg/m2. It is assumed that Adriamycin, or other anthracycline derivatives, are still active when the cardiotoxic level is reached. In this retrospective study of 171 patients with various metastatic malignant tumors, the total dose of Adriamycin given to the patients and the reasons for withholding the treatment have been analyzed. Overall, among the 171 patients treated by Adriamycin-containing combination chemotherapy, 54 objective remissions (31%) were observed. Remissions were more frequent in untreated patients (52%) than in previously treated patients (20%). In 36 of 54 patients the disease progressed before the cumulative cardiotoxic level was reached. Adriamycin could be discontinued in only 18 patients still in remission. 8 of 171 patients received more than 450 mg/m2 Adriamycin without cardiotoxic side effects being observed. Among the 171 patients, cardiotoxicity probably related to anthracyclines developed in 5 cases (3%), in all cases at a level below 450 mg/m2. These results suggest that in most cases Adriamycin becomes inactive before the dose-limiting cumulative cardiotoxic level is reached.
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PMID:[Is the use of adriamycin (doxorubicin) limited by its cardiotoxicity?]. 400 4

Adriamycin (ADM) is a very effective antimitotic agent but its use is limited by its cardiotoxicity. New anthracycline drugs such as aclacinomycin A (ACMA) have been developed and have to be compared with ADM after chronic experimental intoxication. Three groups of randomised rats were compared: the ADM group receiving 2 mg/kg/week X 13 by intraperitoneal injection; the ACMA group receiving 4 mg/kg/week X 13 and a control group: 7 rats. The rats were autopsied at the 20th week. The heart was stopped in diastole and fixed by aortic retroinfusion of glutaraldehide for electronic microscopy (EM). In the ADM group, mean weight fell from the 4th week and mortality was 11/16 at 20 weeks. Voluminous haemorrhagic ascites was associated with peritoneal fibrosis in 12/16. Cardiac failure was observed in 4 cases but on light microscopy (LM) myofibril degeneration was constant and focal without sarcoplasmic reticulum or mitochondrial changes on EM. In the ACMA group the loss of weight occurred at 10 weeks and mortality due to toxicity was nil. There was no cardiac failure; myocytolysis was absent on LM and slight in 4/13 cases on EM with a moderate dilatation of the sarcoplasmic recticulum and presence of numerous residual bodies in the striated skeletal fibres in 5/15 cases. In this study, the ACMA had very little cardio and general toxicity in comparison with ADM. The technique of fixing the heart by retrograde infusion prevents, as far as possible, artefacts on EM affecting mainly the mitochondria.
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PMID:[Comparison of the cardiotoxicity of adriamycin and aclacinomycin A in the rat. Optical and electron microscopic study]. 641 94

Anthracycline antibiotic (Rubidomycin and Adriamycin) are often used for treatment of acute leukemia and variety of solid tumors. The use of greater doses of these agents is mostly limited by the damage of the cardiac muscle and by heart failure. The Rubidomycin cardiac toxicity analysis of children with acute leukemia has been considered in this paper. The results were obtained by investigating 53 patients who received this drug. They were classified in subgroups in relation to the total dose administered. Acute or chronic myocardial damage appeared in 6 children. The subgroup incidence of damage is directly proportional to the total dose administered.
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PMID:[Cardiotoxic effect of anthracycline antibiotics]. 668 Mar

Combined chemohormonal therapy of metastatic prostate cancer has not been previously evaluated in patients failing primary hormones (estrogens and/or orchiectomy). The combination of Adriamycin and high-dose diethylstilbestrol diphosphate (Stilphostrol) was studied in 19 heavily pretreated patients, to document toxicity and patient acceptability. Major toxicity was myelosuppression, cardiac failure and venous thrombosis. Clinical improvement was noted in 10/16 (63%) of evaluable patients. Patients with pre-existing cardiac disease or venous thrombosis are not suitable for this therapy.
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PMID:Chemohormonal therapy of metastatic prostate cancer. A pilot study. 686 Oct 82

An 18-year-old man had had an osteogenic sarcoma of the distal tibia at age 16. Below-knee amputation was carried out and followed by adjuvant chemotherapy with Adriamycin, vincristine, methotrexate, Cytoxan, and melphalan. One month after termination of chemotherapy, he died suddenly while playing tennis. Documented ventricular fibrillation was unresponsive to cardiopulmonary resuscitation. Myocardial fibrosis ("cardiomyopathy") was the only significant anatomic finding at autopsy. The occurrence of sudden death without antecedent cardiac failure may have been related to strenuous physical activity in this patient who had received combined adjuvant chemotherapy.
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PMID:Sudden cardiac death following adriamycin therapy. 694 Jun 49

The aim of this study was to detect the cardiotoxicity of Adriamycin (ADM) by the evolution of the systolic time intervals (STI). The PEP/LVET ratio represents an easy and reproducible index of myocardial function. The more important this increase, the greater the risk of developing heart failure. A significant correlation exists between the variation of this ratio and the total administered dose, but the correlation coefficient is low. A heart failure may appear for doses of ADM under 500 mg/m2 but it is preceded by an increase of the index. In the absence of a significant modification, the generally admitted maximum dose of 550 mg/m2 may be exceeded. In case of a ratio increase in excess of 0.08 it will be necessary to balance the potential benefits of treatment with the hazards of cardiac failure. The PEP/LVET ratio allows proceeding with the cytostatic treatment in increased security by selecting the patients at high risk for cardiac failure.
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PMID:Adriamycin cardiotoxicity. Prognostic value of the systolic time intervals. 698 May 47


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