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

Right ventricular endomyocardial biopsy, right heart catheterization, and systolic time intervals were done in 33 adult patients receiving doxorubicin (AdriamycinTM). Doxorubicin administration was associated with a dose-related increase in the degree of myocyte damage, and 27 of 29 patients biopsied at doses greater than or equal to 240 mg/m2 had doxorubicin-associated degenerative changes identified on biopsy. The pre-ejection period to left ventriculr ejection time ratio (PEP/LVET) showed a threshold phenomenon and did not begin to increase until a total dose of 400 mg/m2 had been reached. Seven patients with catheterization-proven heart failure had a significantly greater amount of myocyte damage on biopsy than dose-matched control subjects (P less than 0.01). Preveious mediastinal radiation appeared to potentiate the doxorubicin-associated degenerative process. Mediastinal radiation and age greater than or equal to 70 years appeared to be risk factors for doxorubicin-associated heart failure. Dose limitation by combined clinical, noninvasive, invasive, and morphologic criteria offered an advantage over empirical dose limitation or dose limitation by PEP/LVET alone.
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PMID:Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. 62 45

The effects of cardiomyoplasty were evaluated with multiple-gated equilibrium radionuclide angiocardiography and catheterization in a canine model of chronic heart failure. Doxorubicin was administered to 12 dogs at a dose of 1 mg/kg/wk intravenously for 10 weeks. Left ventricular ejection fraction was reduced from a mean of 53.6% +/- 3.4% to 33.5% +/- 2.3% preoperatively. Two dogs died of presumed arrhythmia during this period. Cardiomyoplasty with the left latissimus dorsi muscle was performed on 10 dogs. The muscle was wrapped around both the left and right ventricles. Five dogs died of infection or arrhythmia after the operation. Postoperatively the muscle remained unstimulated for 2 weeks to allow adhesion to the heart. After this period, the latissimus dorsi muscle was conditioned by a progressive stimulation protocol. After the muscle was conditioned, multiple-gated equilibrium radionuclide angiocardiography studies showed that left ventricular global ejection fraction was 18.4% +/- 7.2% at 0 volts (nonstimulation), 26.2% +/- 3.7% at 5-volt stimulation (p less than 0.05), and 31.0% +/- 5.4% at 10-volt stimulation (p less than 0.05). Regional ejection fractions in low lateral, apical, and low septal regions at 5 volts and 10 volts were higher than those at 0 volts (p less than 0.05). Regional wall motion (percent radial shortening) of the low lateral region was higher than that during nonstimulation (p less than 0.05). Peak emptying rate was 2.07 +/- 0.95 end-diastolic counts per second at 0-volt, 3.10 +/- 0.67 at 5-volt, and 3.34 +/- 0.89 at 10-volt stimulation (p less than 0.05). Peak filling rate was 1.81 +/- 0.52 end-diastolic counts per second at 0-volt, 2.67 +/- 1.18 at 5-volt, and 3.11 +/- 0.65 at 10-volt stimulation (p less than 0.05). Cardiac catheterization data showed a nonsignificant increase in left ventricular rate of pressure rise with increasing voltage (1302 +/- 355 mm Hg/sec at 0 volts, 1450 +/- 413 mm Hg/sec at 5 volts, and 1568 +/- 455 mm Hg/sec at 10 volts). Left ventricular systolic pressures were unchanged. End-diastolic pressures decreased (11.2 +/- 1.48 mm Hg at 0 volts, 10.4 +/- 2.30 mm Hg at 5 volts, and 9.6 +/- 1.52 at 10 volts; p less than 0.05). These data show that cardiomyoplasty can improve indices of systolic and diastolic function in a canine model of chronic heart failure.
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PMID:Effects of dynamic cardiomyoplasty on indices of left ventricular systolic and diastolic function in a canine model of chronic heart failure. 159 87

Experimental work on the mechanisms of acute doxorubicin-induced cardiotoxicity may contribute to a better understanding of the clinical problem of cardiac failure after treatment with anthracycline derivatives. We studied aortic pressure and heart rate continuously for 1 h following a bolus injection of doxorubicin (1 mg/kg) in 7 dogs. In contrast with previous studies in intact animals, no anesthesia was used in order to eliminate possible interactions of doxorubicin with other drugs. One minute after doxorubicin injection a severe hypotension was observed, the average nadir in systolic and diastolic pressure being 62% and 42% of initial values. Surprisingly, the decrease in arterial blood pressure was not accompanied by cardiac acceleration. Doxorubicin, apparently interferes with the normal regulation of heart rate through the baroreceptor control system. Although several theories have been put forward regarding the mechanisms governing acute anthracycline cardiotoxicity, our knowledge of the phenomenon is still incomplete.
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PMID:Acute circulatory effects of doxorubicin in the conscious dog. 315 44

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

The hearts of 16 autopsy cases with a past history of administration of anthracycline antitumor drugs (DNR, ADR and ACM) and a sign of cardiac failure were investigated morphologically. In macroscopic observation, both ventricles were more or less dilated with thinning of the ventricular wall. Mural thrombi were recognized in the left ventricle of 2 cases. Histologically, the myocardial lesions could be roughly classified into two groups, a) myocardial changes in cases with rapidly developed cardiac failure (acute form), and b) myocardial changes in cases with relatively slowly developed cardiac failure. In acute form, myocardial cells showed marked swelling with dilatation of central sarcoplasmic core, marked reduction of myofibrils, vacuolization of cytoplasm and enlargement of nucleus accompanied by distinct large nucleolus. Necrotic myocardial cells were scattered among these degenerative cells. These degenerative and necrotic cells were distributed diffusely in both ventricular walls, but were more frequent in the left ventricular wall than in the right one. Inflammatory cell infiltration was also recognized not only in the myocardium, but also in the endocardium and epicardium. In chronic form, on the other hand, atrophy and attenuation of myocardial cells with a hypereosinophilic change of the cytoplasm and an increase in number of brown pigments, and marked reduction of myocardial cells were most common findings. These changes of chronic form, however, could not be identified as the specific changes of anthracycline cardiotoxicity. Fibrosis was hardly seen in the myocardium of both acute and chronic forms.
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PMID:Anthracycline induced myocardial damage. An analysis of 16 autopsy cases. 346 40

The influence of increasing doses of doxorubicin on the heart was examined in 30 patients with solid tumors, M-mode echocardiography being used to evaluate left ventricular contractility. The function of the left ventricle remained normal in 26 subjects, whereas four patients had evidence of cardiotoxicity after cumulative doses of 220, 380, 420, and 450 mg/m2. Transient overt heart failure was noted in one subject only. Doxorubicin cardiotoxicity can be detected by M-mode echocardiography, a simple and non-invasive technique, prior to the appearance of overt congestive heart failure. Patients demonstrating left ventricular dysfunction are probably not candidates for receiving further therapy with anthracycline antibiotics. Limitation of M-mode echocardiography include a 28% incidence of inadequate studies in this group of patients, and a relative inaccuracy of the technique in evaluating patients with prior myocardial infarction.
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PMID:Early detection of doxorubicin cardiotoxicity by M-mode echocardiography. 747 16

Echocardiographic reports on 144 adults receiving anthracycline therapy and 18 controls were reviewed for the possible relationship between dosage and ejection fractions. The cardiotoxicity of each anthracycline drug was evaluated as follows: Pirarubicin = 0.8, Mitoxantrone = 3.4, Daunorubicin = 0.5, Aclarubicin = 0, and Epirubicin = 0.6 with Doxorubicin = 1 as a control. As a whole, the ejection fractions, which decreased subsequently compared with increasing amount of dosage, showed a remarkable decrease at the dosage level of 600 mg/m2. However, the ejection fractions differed among individual patients. It was predicted that heart failure would not develop when the ejection fractions exceeded 55%. It is desirable to stop anthracycline therapy when the ejection fractions drop to 55%.
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PMID:[Echocardiographic evaluation of cardiotoxicity induced by anthracycline therapy]. 908 92

The role of the stimulatory guanine nucleotide-binding protein (Gs) in heart failure is unclear. We therefore determined the amount of protein and mRNA of Gs in the failing myocardium using two animal models: the BIO 53.58 hamster, a model of genetic cardiomyopathy, and adriamycin-treated rats (ADR rats), a model of secondary cardiomyopathy. The maximal number of myocardial beta-adrenoceptors in the BIO 53.58 hamsters as well as in the ADR rats was significantly lower than that in the respective controls, indicating that the beta-adrenoceptors were down-regulated in heart failure. Analysis by Western blot and Northern blot revealed a significant decrease in Gs protein and mRNA in the BIO 53.58 hamsters relative to the control. There were no differences in the level of Gs protein or mRNA in the ADR rats vs the controls. The functional activity of Gs was investigated by measuring adenylate cyclase activity. The activity of adenylate cyclase in response to stimulation by sodium fluoride or forskolin was decreased in the BIO 53.58 hamsters relative to control animals, whereas no differences were observed in the ADR rats vs the controls. Thus, alterations in Gs in the failing heart appear to differ according to its cause.
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PMID:Stimulatory guanine nucleotide-binding protein in failing heart of hamsters and rats. 963 57

We describe a case of postoperative congestive heart failure in a young woman of physical class ASA 1, following breast cancer surgery. Preoperatively she had been treated with doxorubicin (Adriamycin) 450 mg.m-2, total dose, associated with breast and ovarian radiotherapy. This association was probably the cause of postoperative heart failure. Twenty-four hours after surgery, a two-dimensional echocardiography showed a severe left ventricular dysfunction, whereas preoperative clinical assessment was unremarkable. Doxorubicin cardiotoxicity can be acute, subacute and delayed as in our case. Clinical assessment and ECG are not sensitive indicators of such cardiac damage. Preoperative echography is the technique of choice for the evaluation of the cardiac status of a patient treated with a high cumulative dose of doxorubicin and mediastinal irradiation.
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PMID:[Acute cardiogenic postoperative edema after doxorubicin (adriamycin) chemotherapy]. 975 Jun 82

Doxorubicin is cardiotoxic and its use must be monitored carefully. Incidence of refractory cardiac failure is shown to increase once the cumulative dose exceeds 450 mg/m2. However, significant decline of ejection fraction (EF) may occur even at lower dose levels. EF was monitored using Multigated Radionuclide Angiography (MUGA) scan of all consecutive lung cancer patients, treated with Doxorubicin based regimens. Thirteen of 82 patients showed a significant (more than 15%) decline of left ventricular EF. The dose of doxorubicin producing this decline ranged between 91-180 mg/m2. Actual decline in EF ranged between 16-45%. Only 5 of 13 patients developed symptoms attributable to the cardiac disease. Doxorubicin can alter EF significantly in lung cancer patients at levels well below which are considered 'safe'. The reason for massive decline in ejection fraction in these patients has been hypothesized.
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PMID:Doxorubicin cardiomyopathy in lung cancer patients. 981 76


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