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Anthracycline chemotherapy is a widely-used and effective treatment for a wide spectrum of childhood cancers. Its use is limited
by associated progressive and clinically significant cardiotoxic effects. Onset can be acute, early, or late. While acute
onset is rare, long-term survivors have significantly elevated rates of cardiac morbidity and mortality. Major complications
include cardiomyopathy, coronary artery disease, and atherosclerosis. Means of prevention and treatment continue to be explored
including limiting cumulative anthracycline dose, controlling the rate of administration, and using liposomal preparations
and novel anthracycline analogues. Dexrazoxane prior to anthracycline chemotherapy has been shown to significantly lower rates
of elevated serum cardiac troponin levels, a marker of myocyte injury, indicating a cardioprotective effect. Pilot studies
indicate that exercise interventions may also be beneficial in long-term survivors with cardiac damage. Support and study
of this population to decrease the morbidity and morality associated with anthracycline-induced cardiotoxicity is indicated
in a time sensitive fashion. 相似文献
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T Sakamaki T Uchiyama Y Fujibayashi Y Sato A Osaku K Ogawa T Ebuchi N Katsumata K Kanmatsuse N Kajiwara 《Journal of cardiology》1992,22(1):201-210
Ten patients with malignant diseases whose mean age was 20.0 +/- 13.2 years received anthracycline derivatives therapy and were evaluated for their left ventricular systolic and diastolic functions by computer-assisted digitized M-mode echocardiography. Fractional shortening (%FS), a parameter of systolic function, was measured. The first derivative of left ventricular dimension change (peak LV dD/dt), posterior wall thinning (peak LVPW thinning rate) and interventricular septum thinning (peak IVS thinning rate) were used as indices of diastolic function. Blood pressure (BP) was measured noninvasively at the end of the echocardiographic examination and hemoglobin concentration (Hb) was measured on the same day. These examinations were performed immediately before administration of anthracycline and one week and one month after the last administration. Statistical analyses were performed using the Student's t-test. The mean BP, HR, LVDd, LVDs, LVPW and IVS remained unchanged following the drug administration. %FS did not change significantly; 36.8 +/- 6.3%, before the administration, 35.3 +/- 6.5%, one week after the administration, and 36.5 +/- 5.1%, one month after the administration. Peak LVdD/dt and the peak LVPW thinning rate decreased appreciably from 4.46 +/- 1.10 to 3.76 +/- 1.08, and from 7.99 +/- 1.55 to 6.41 +/- 1.04, respectively, one week after the administration. The peak IVS thinning rate decreased from 3.54 +/- 0.81 to 2.99 +/- 0.79 after one week (p < 0.01). All of these values returned to the control levels in one month after the drug administration. We concluded that the indices of left ventricular diastolic function were more sensitive for detecting cardiac impairment than those of systolic function during the course of anthracycline therapy. 相似文献
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Anthracyclines, such as doxorubicin and idarubicin, remain an important class of chemotherapeutic agents. Unfortunately, their efficacy in treating cancer is limited by a cumulative dose-dependent cardiotoxicity, which can cause irreversible heart failure. In this review, we discuss the pathogenesis and incidence of anthracycline-induced cardiotoxicity as well as methods to detect, prevent and treat the condition. 相似文献
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Anthracyclines are drugs with widespread applications on the chemotherapy of cancer. Cardiotoxicity is an important side effect of these drugs, well known for doxorubicin, the most representative of this group of drugs. Dysrhythmias and heart failure are the most important among the toxic effects of anthracyclines and are dependent on cumulative doses reason why WHO established maximal doses for the different anthracyclines. Pathogenic hypothesis about the mechanism of the myocardial lesion induced by anthracyclines include the production of free oxygen radicals, alterations of energetic metabolism and disturbances of calcium and sodium exchange at membrane level. Early detection of the toxicity of these drugs is of utmost importance. Electrocardiography has low sensitivity and specificity. Echocardiography gives specific information about previous cardiac pathology and enables the detection of complication of the basic neoplastic disease. However, detection of early changes of left ventricular function is not accomplished so well, as it is with equilibrium radionuclide angiography. Left ventricular ejection fraction is the method of choice in the early detection of cardiotoxicity of these drugs, and its frequent evaluation enables to individualize the doses in each patient, and so, a most accurate use of the therapeutic potential of the anthracyclines. Radionuclide angiography has some important indications on the selection of patients for treatment with anthracyclines, namely: to identify patients that must be excluded from the treatment; select patients at risk of congestive heart failure; to decide the appropriate moment to stop the drugs; change the therapeutic schema, etc.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Doxorubicin is known to cause cardiomyopathy and congestive heart failure (CHF) upon chronic administration. A major obstacle
to doxorubicin-containing multiagent therapies pertains to the possible development of cardiomyopathy and CHF at lower than
expected cumulative doses of doxorubicin. For example, the cardiac toxicity of doxorubicin is aggravated by the anti-HER2
antibody Trastuzumab or by the tubulin-active taxane paclitaxel; however, the mechanisms by which Trastuzumab and paclitaxel
aggravate doxorubicin-induced cardiotoxicity are mechanistically distinct: Trastuzumab interferes with cardiac-specific survival
factors that help the heart to withstand stressor agents like anthracyclines, while paclitaxel acts by stimulating the formation
of anthracycline metabolites that play a key role in the mechanism of cardiac failure. Here, we briefly review the molecular
mechanisms of the cardiotoxic synergism of Trastuzumab or paclitaxel with doxorubicin, and we attempt to briefly outline how
the mechanistic know-how translates into the clinical strategies for improving the safety of anthracycline-based multiagent
therapies. 相似文献
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N R Bachur 《Cancer treatment reports》1979,63(5):817-820
The anthracycline antibiotics show evidence of numerous interactions with cellular components and participation in several metabolic pathways. Small structural changes in the antibiotic molecule can produce major changes in intracellular localization and interaction. To date, we find that all of the anthracycline antibiotics form free radical intermediates through the catalysis of microsomal and nuclear electron-transport machinery. NADPH cytochrome P-450 reductase catalyzes the free radical formation. The free radical intermediates ("site-specific free radicals") may be causative of both toxicity and pharmaceutic action. The free radical intermediates degrade nonenzymatically to 7-deoxyaglycone metabolites which prove the existence of the free radical in vivo. 相似文献
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John V McGowan Robin Chung Angshuman Maulik Izabela Piotrowska J Malcolm Walker Derek M Yellon 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2017,31(1):63-75
Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane. New treatments exploiting the ErbB or other novel pro-survival pathways, such as conditioning, are on the cardioprotection horizon. Even in the forthcoming era of targeted cancer therapies, the substantial proportion of today’s anthracycline-treated cancer patients may become tomorrow’s cardiac patient. 相似文献
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Y Cottin I L'huillier O Casasnovas C Geoffroy D Caillot M Zeller E Solary H Guy J E Wolf 《European journal of echocardiography》2000,1(3):180-183
BACKGROUND: Anthracyclines are effective anti-cancer agents, but their therapeutic value is limited by their myocardial toxicity. We assessed the physiological responses of stress echocardiography at low doses of dobutamine (DSE) in patients treated with anthracycline. METHODS AND RESULTS: In a prospective study, 28 patients were studied before and 1 month after the end of chemotherapy. All patients had normal ejection fraction (EF) at rest before therapy and the mean dose of anthracycline was 212+/-15 mg/m(2). Echocardiographic Doppler studies were performed before and during dobutamine infusion (5 and 10 microg/kg per min). Rest echocardiography demonstrated a significant decrease of EF between the two examinations in ejection fraction (67+/-3% vs. 61+/-3%, P<0.001). The increase of the EF during dobutamine infusion was higher after chemotherapy compared to the initial examination (19+/-3% vs. 29+/-3%: P<.05). No difference in EF was observed at 10 microg/kg per min between before and after chemotherapy. In contrast, at rest no difference in diastolic parameters was observed between the two examinations. Moreover, a significant decrease of the peak E and the ratio E/A was observed during dobutamine infusion after chemotherapy (93+/-4 cm/s vs. 79+/-5 cm/s and 1.3+/-0.1 vs. 1.0+/-0.1, respectively;P<0.05). CONCLUSION: Stress echocardiography may prove to be a sensitive technique and useful non-invasive approach for evaluating subclinical anthracycline cardiotoxicity. 相似文献
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Since patients exhibit both acute and chronic cardiac toxic effects from Adriamycin, the salient characteristics of the reported animal models for both acute and chronic cardiotoxicity are reviewed. This review reveals that while the pathology of these models is often well-characterized, the physiologic, biochemical, and nutritional variables are, in general, poorly defined. 相似文献
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Catecholamine cardiotoxicity 总被引:34,自引:0,他引:34
G Rona 《Journal of molecular and cellular cardiology》1985,17(4):291-306
The morphologic-functional correlative studies that we have carried out in the past 25 years with the various catecholamines have served as an example for analyzing myocardial reaction patterns and the reactions of the cardiac muscle cells to insult. These studies disclosed the unique nature of isoproterenol in producing 'infarct-like' myocardial necrosis. It appears that the pathogenesis of the catecholamine-induced myocardial necrosis is multifactorial. Our early studies suggested the role of relative hypoxia. Later studies by using extracellular fine structural protein tracers demonstrated the importance of microcirculatory effects as well as, in the norepinephrine model, that of early sarcolemmal membrane permeability alteration. The Ca2+ overload theory is supported not only by the experimental observations but also by its successful application in clinical cardiology. A new contribution is the recognition of catecholamine oxidation products in producing myocardial injury. Experimental data indicate that catecholamines play an important role in reperfusion and ischemic myocardial injuries. The sequence of events demonstrated by our studies with catecholamines might represent a common pathway in the evolution of myocardial changes in humans who develop myocardial lesions without narrowing or obstruction of coronary arteries. Investigation in the field of molecular and cellular cardiology has led to a better understanding of current clinical problems and helped to devise procedures for the prevention and management of human myocardial disorders. The isoproterenol-induced myocardial necrosis served as model to Professor A. Fleckenstein to formulate the Ca2+ overload theory of myocardial injury and develop a series of now widely used Ca2+ antagonistic drugs for the management and the prevention of human myocardial diseases. 相似文献