Is paclitaxel less cardiotoxic in the treatment of breast cancer before or after doxorubicin? / Qual estratégia terapêutica é menos cardiotóxica no tratamento do câncer de mama: uso de paclitaxel antes ou depois da doxorrubicina?

Background: The combination of doxorubicin (DOX) with paclitaxel (PTX) effectively treats breast cancer (BC). However, DOX-associated cardiotoxicity (CTX) is aggravated by the use of PTX. Consensus is lacking about which drug sequence involves the most CTX. Objectives: To evaluate whether DOX followed by PXT or the reverse sequence has the greatest cardiotoxic potential in the treatment of BC. Methods: Prospective study of women with primary BC who received four cycles of DOX and 12 infusions of PTX. Participants were divided into Group 1 (G1; PXT before DOX) and Group 2 (G2; DOX before PXT) at the discretion of the oncologist. CTX was defined as an absolute reduction in left ventricular ejection fraction (LVEF) > 10% to a value <53%. Patients underwentclinical evaluations and echocardiography before treatment (Phase 1) and one year after treatment (Phase 2). Results: Sixty-nine women were evaluated: 19 in G1 and 50 in G2. The groups had similar clinical characteristics. The doses of radiation, DOX, and PTX used were similar. Eight (11.6%) patients developed CTX: two (10.5%) in G1 and six (12.0%) in G2 (p=0.62). The mean LVEF was similar between groups in Phase 1 (G1=65.1±3.5%; G2=65.2±3.9%; p=0.96), with a significant reduction noted after one year in both groups: G1=61.4±8.1% (p=0.021) and G2=60.8±7.6% (p<0,001). Although lower, mean LVEF remained similar between groups after Phase 2 (p=0.79). Conclusions: In women with BC who underwent chemotherapy, the incidence of CTX at the end of the first year of treatment was similar regardless of whether DOX was used before or after PTX. (AU)

Recomendaciones para el manejo de la cardiotoxicidad relacionada con el tratamiento del cáncer. Primera parte / Recommendations for the management of cardiotoxicity related to cancer treatment. Part one / Recomendações para a gestão de cardiotoxicidade relacionada com o tratamento do câncer. Primeira parte

Las nuevas terapias oncológicas han logrado aumentar la sobrevida del paciente con cáncer, observando, sin embargo, un incremento de la morbilidad y mortalidad vinculadas a sus efectos secundarios. El desarrollo de eventos cardiovasculares adversos impacta negativamente en el pronóstico durante el tratamiento del cáncer, pero también en los supervivientes al cáncer, donde las enfermedades cardiovasculares (ECV) y las segundas neoplasias son la principal causa de muerte1-5. La cardiotoxicidad inducida por el tratamiento del cáncer se define como el conjunto de ECV derivadas de los tratamientos oncológicos. Su manifestación es variada e incluye el desarrollo de disfunción ventricular, insuficiencia cardíaca (IC), isquemia miocárdica, hipertensión arterial y arritmias, entre otras. Puede ser consecuencia tanto del efecto directo del tratamiento sobre la estructura y función cardíacas, como del desarrollo acelerado de ECV6-9. Frecuentemente se utiliza el término cardiotoxicidad como sinónimo de disfunción ventricular por quimioterapia (DV-QT). Dado que la cardiotoxicidad abarca un espectro más amplio de afectación cardiovascular, creemos conveniente hablar de DV-QT para referirnos a la afectación de la función sistólica del ventrículo izquierdo. La DV-QT y el desarrollo de IC representan una de las complicaciones más temidas por su impacto pronóstico en la esfera cardiovascular y oncológica, dado que limitan el arsenal terapéutico para el tratamiento del cáncer5,10. Han sido creadas diversas sociedades de cardio-onco-hematología con el fin de generar recomendaciones de práctica clínica y formar profesionales capacitados para el manejo de las complicaciones cardiovasculares del tratamiento del cáncer11. La cardio-oncología es una disciplina en creciente y continuo desarrollo. Creemos que es fundamental realizar tareas de formación médica continua, así como también estimular el trabajo conjunto de diversas especialidades para brindar una mejor asistencia. Este texto es el resultado del trabajo de un equipo multidisciplinario que incluye cardiólogos, hematólogos y oncólogos, y pretende brindar información a los integrantes del equipo de salud involucrados en la asistencia de pacientes oncológicos. Debido a su extensión, hemos decidido fraccionar el contenido en tres partes para facilitar su publicación.

New oncological therapies have been successful in increasing cancer patient survival, but they have also led to an increase in morbidity and mortality linked to their side effects. During cancer treatment, the development of cardiovascular side effects has a negative impact in prognosis, but also in cancer survivors, in whom cardiovascular diseases and secondary malignancies are the main cause of death. Cancer related cardiotoxicity is defined as the development of cardiovascular diseases related to cancer treatment. Clinical presentation is broad involving ventricular dysfunction, heart failure, myocardial ischemia, arterial hypertension and arrhythmias among others. This may result from the direct cardiovascular effect of a cancer treatment or accelerated development of cardiovascular diseases. Frequently, in the literature cardiotoxicity and chemotherapy related ventricular dysfunction are used as synonyms. However, cardiotoxicity includes a broad spectrum of cardiovascular manifestations, thus in this text we refer to chemotherapy related ventricular dysfunction as the presence of left ventricular systolic impairment. Chemotherapy related ventricular dysfunction and heart failure are two of the most feared complications of cancer treatment due to its impact on cardiovascular and oncological prognosis, affecting treatment options. Numerous worldwide cardio-onco-hematology societies have emerged to generate clinical practice guidelines and improve the diagnosis and evaluation of cardiovascular cancer treatment side effects. Cardio-Oncology is a discipline in continuous growth and development. We strongly believe that continuum medical education and a multidisciplinary approach is necessary to provide a quality health care. This text is the result of a multidisciplinary work involving cardiologists, hematologists and oncologists. It is our goal to provide information to the health care team involved in the assistance of cancer patients. Due to its extension, it will be published in three parts.

O desenvolvimento de novas terapias oncológicas levou a um aumento na sobrevida dos pacientes, mas ao mesmo tempo traz consigo morbidades relacionadas aos tratamentos. O desenvolvimento de efeitos cardiovasculares adversos tem um impacto negativo no prognóstico dos pacientes em tratamento, bem como nos pacientes considerados curados, nos quais doença cardiovascular e malignidades secundárias são as principais causas de morte. Cardiotoxicidade relacionada ao câncer é definida como o desenvolvimento de doença cardiovascular secundária ao tratamento. A gama de apresentações clínicas é ampla, podendo se manifestar como disfunção ventricular, insuficiência cardíaca, isquemia miocárdica, hipertensão arterial, arritmias, entre outras. Isto pode ser resultante de desenvolvimento e progressão acelerados de doença cardiovascular ou por efeito direto das terapias. Frequentemente é dito na literatura que cardiotoxicidade e disfunção ventricular relacionada à quimioterapia são sinônimos. Entretanto, cardiotoxicidade engloba um amplo espectro de manifestações cardiovasculares. Neste texto, portanto, nos referimos à disfunção ventricular causada por quimioterápicos exclusivamente como a presença de disfunção sistólica ventricular esquerda. Disfunção ventricular relacionada à quimioterapia e insuficiência cardíaca são duas das mais temidas complicações do tratamento oncológico devido ao seu impacto no prognóstico cardiovascular e oncológico, podendo afetar ainda a escolha e manutenção das opções terapêuticas. Diversas sociedades cardio-onco-hematológicas surgiram ao redor do mundo com o objetivo de gerar diretriz clínicas práticas e melhorar o diagnóstico e tratamento das complicações cardiovasculares resultantes das terapias oncológicas. A cardio-oncologia é uma disciplina em contínuo crescimento e desenvolvimento. Nós acreditamos fortemente que educação médica continuada e uma abordagem multidisciplinar são necessárias para um cuidado médico de qualidade. Este texto é o resultado de um trabalho multidisciplinar envolvendo cardiologistas, hematologistas e oncologistas. Nosso objetivo é de oferecer informação à equipe de cuidados em saúde envolvido na assistência destes pacientes. Devido à sua extensão, este texto será publicado em três partes.

Recomendaciones para el manejo de la cardiotoxicidad relacionada con el tratamiento del cáncer. Segunda parte / Recommendations for the management of cardiotoxicity related to cancer treatment. Part two / Recomendações para a gestão de cardiotoxicidade relacionada com o tratamento do câncer. Primeira [i.e. Segunda] parte

Las nuevas terapias oncológicas han logrado aumentar la sobrevida del paciente con cáncer, observando, sin embargo, un incremento de la morbilidad y mortalidad vinculadas a sus efectos secundarios. El desarrollo de eventos cardiovasculares adversos impacta negativamente en el pronóstico durante el tratamiento del cáncer, pero también en los supervivientes al cáncer, donde las enfermedades cardiovasculares (ECV) y las segundas neoplasias son la principal causa de muerte1-5. La cardiotoxicidad inducida por el tratamiento del cáncer se define como el conjunto de ECV derivadas de los tratamientos oncológicos. Su manifestación es variada e incluye el desarrollo de disfunción ventricular, insuficiencia cardíaca (IC), isquemia miocárdica, hipertensión arterial (HTA) y arritmias, entre otras. Puede ser consecuencia tanto del efecto directo del tratamiento sobre la estructura y función cardíacas, como del desarrollo acelerado de enfermedad cardiovascular6-9. Con frecuencia, se utiliza el término cardiotoxicidad como sinónimo de disfunción ventricular por quimioterapia (DV-QT). Dado que la cardiotoxicidad abarca un espectro más amplio de afectación cardiovascular, creemos conveniente hablar de DV-QT para referirnos a la afectación de la función sistólica del ventrículo izquierdo. La DV-QT y el desarrollo de IC representan una de las complicaciones más temidas por su impacto pronóstico en la esfera cardiovascular y oncológica, dado que limitan el arsenal terapéutico para el tratamiento del cáncer5,10. Han sido creadas diversas sociedades de cardio-onco-hematología con el fin de generar recomendaciones de práctica clínica y formar profesionales capacitados para el manejo de las complicaciones CV del tratamiento del cáncer11. La cardio-oncología es una disciplina en creciente y continuo desarrollo. Creemos que es fundamental realizar tareas de formación médica continua, así como también estimular el trabajo conjunto de diversas especialidades para brindar una mejor asistencia. Este texto es el resultado del trabajo de un equipo multidisciplinario que incluye cardiólogos, hematólogos y oncólogos, y pretende brindar información a los integrantes del equipo de salud involucrados en la asistencia de pacientes oncológicos. Debido a la extensión del presente texto, hemos decidido fraccionar el contenido en tres partes para facilitar su difusión.

New oncological therapies have been successful in increasing cancer patient survival, but they have also led to an increase in morbidity and mortality linked to their side effects. During cancer treatment, the development of cardiovascular side effects has a negative impact in prognosis, but also in cancer survivors, in whom cardiovascular diseases and secondary malignancies are the main cause of death. Cancer related cardiotoxicity is defined as the development of cardiovascular diseases related to cancer treatment. Clinical presentation is broad involving ventricular dysfunction, heart failure, myocardial ischemia, arterial hypertension and arrhythmias among others. This may result from the direct cardiovascular effect of a cancer treatment or accelerated development of cardiovascular diseases. Frequently, in the literature cardiotoxicity and chemotherapy related ventricular dysfunction are used as synonyms. However, cardiotoxicity includes a broad spectrum of cardiovascular manifestations, thus in this text we refer to chemotherapy related ventricular dysfunction as the presence of left ventricular systolic impairment. Chemotherapy related ventricular dysfunction and heart failure are two of the most feared complications of cancer treatment due to its impact on cardiovascular and oncological prognosis, affecting treatment options. Numerous worldwide cardio-onco-hematology societies have emerged to generate clinical practice guidelines and improve the diagnosis and evaluation of cardiovascular cancer treatment side effects. Cardio-Oncology is a discipline in continuous growth and development. We strongly believe that continuum medical education and a multidisciplinary approach is necessary to provide a quality health care. This text is the result of a multidisciplinary work involving cardiologists, hematologists and oncologists. It is our goal to provide information to the health care team involved in the assistance of cancer patients. Due to its extension, it will be divided in three parts.

O desenvolvimento de novas terapias oncológicas levou a um aumento na sobrevida dos pacientes, mas ao mesmo tempo traz consigo morbidades relacionadas aos tratamentos. O desenvolvimento de efeitos cardiovasculares adversos tem um impacto negativo no prognóstico dos pacientes em tratamento, bem como nos pacientes considerados curados, nos quais doença cardiovascular e malignidades secundárias são as principais causas de morte. Cardiotoxicidade relacionada ao câncer é definida como o desenvolvimento de doença cardiovascular secundária ao tratamento. A gama de apresentações clínicas é ampla, podendo se manifestar como disfunção ventricular, insuficiência cardíaca, isquemia miocárdica, hipertensão arterial, arritmias, entre outras. Isto pode ser resultante de desenvolvimento e progressão acelerados de doença cardiovascular ou por efeito direto das terapias. Frequentemente é dito na literatura que cardiotoxicidade e disfunção ventricular relacionada à quimioterapia são sinônimos. Entretanto, cardiotoxicidade engloba um amplo espectro de manifestações cardiovasculares. Neste texto, portanto, nos referimos à disfunção ventricular causada por quimioterápicos exclusivamente como a presença de disfunção sistólica ventricular esquerda. Disfunção ventricular relacionada à quimioterapia e insuficiência cardíaca são duas das mais temidas complicações do tratamento oncológico devido ao seu impacto no prognóstico cardiovascular e oncológico, podendo afetar ainda a escolha e manutenção das opções terapêuticas. Diversas sociedades cardio-onco-hematológicas surgiram ao redor do mundo com o objetivo de gerar diretriz clínicas práticas e melhorar o diagnóstico e tratamento das complicações cardiovasculares resultantes das terapias oncológicas. A cardio-oncologia é uma disciplina em contínuo crescimento e desenvolvimento. Nós acreditamos fortemente que educação médica continuada e uma abordagem multidisciplinar são necessárias para um cuidado médico de qualidade. Este texto é o resultado de um trabalho multidisciplinar envolvendo cardiologistas, hematologistas e oncologistas. Nosso objetivo é de oferecer informação à equipe de cuidados em saúde envolvido na assistência destes pacientes. Devido à sua extensão, este texto será dividido em três partes.

Suppression of cardiomyocyte functions by ß-CTX isolated from the Thai king cobra (Ophiophagus hannah) venom via an alternative method

Beta-cardiotoxin (ß-CTX), the three-finger toxin isolated from king cobra (Ophiophagus hannah) venom, possesses ß-blocker activity as indicated by its negative chronotropy and its binding property to both ß-1 and ß-2 adrenergic receptors and has been proposed as a novel ß-blocker candidate. Previously, ß-CTX was isolated and purified by FPLC. Here, we present an alternative method to purify this toxin. In addition, we tested its cytotoxicity against different mammalian muscle cell types and determined the impact on cardiac function in isolated cardiac myocyte so as to provide insights into the pharmacological action of this protein. Methods: ß-CTX was isolated from the crude venom of the Thai king cobra using reverse-phased and cation exchange HPLC. In vitro cellular viability MTT assays were performed on mouse myoblast (C2C12), rat smooth muscle (A7r5), and rat cardiac myoblast (H9c2) cells. Cell shortening and calcium transient dynamics were recorded on isolated rat cardiac myocytes over a range of ß-CTX concentration. Results: Purified ß-CTX was recovered from crude venom (0.53% w/w). MTT assays revealed 50% cytotoxicity on A7r5 cells at 9.41 ± 1.14 µM (n = 3), but no cytotoxicity on C2C12 and H9c2 cells up to 114.09 µM. ß-CTX suppressed the extend of rat cardiac cell shortening in a dose-dependent manner; the half-maximal inhibition concentration was 95.97 ± 50.10 nM (n = 3). In addition, the rates of cell shortening and re-lengthening were decreased in ß-CTX treated myocytes concomitant with a prolongation of the intracellular calcium transient decay, indicating depression of cardiac contractility secondary to altered cardiac calcium homeostasis. Conclusion: We present an alternative purification method for ß-CTX from king cobra venom. We reveal cytotoxicity towards smooth muscle and depression of cardiac contractility by this protein. These data are useful to aid future development of pharmacological agents derived from ß-CTX.(AU)

Plantas cardiotóxicas para ruminantes no Brasil / Cardiotoxic plants affecting ruminants in Brazil

Esta revisão atualiza informações sobre plantas cardiotóxicas que afetam os ruminantes no Brasil. Atualmente, sabe-se que existem pelo menos 131 plantas tóxicas pertencentes a 79 gêneros. Vinte e cinco espécies afetam o funcionamento do coração. As plantas que contêm monofluoroacetato de sódio (Palicourea spp., Psychotria hoffmannseggiana, Amorimia spp., Niedenzuella spp., Tanaecium bilabiatum e Fridericia elegans) causam numerosos surtos de intoxicação, principalmente em bovinos, mas búfalos, ovinos e caprinos são ocasionalmente afetados. A intoxicação por Palicourea marcgravii continua a ser a mais importante devido à ampla distribuição desta planta no Brasil. Novas espécies do gênero Palicourea contendo monofluoracetato de sódio, como Palicourea amapaensis, Palicourea longiflora, Palicourea barraensis, Palicourea macarthurorum, Palicourea nigricans, Palicourea vacillans e Palicourea aff. juruana foram descritas na região amazônica. Na região nordeste, a planta tóxica mais importante para bovinos é Amorimia septentrionalis. No Centro-Oeste, surtos de intoxicação por Niedenzuella stannea foram relatados em bovinos na região do Araguaia e a doença precisa ser melhor investigada quanto à sua ocorrência e importância. Tetrapterys multiglandulosa e Tetrapterys acutifolia, duas plantas que causam fibrose cardíaca, também contêm monofluoracetato de sódio e foram reclassificadas para o gênero Niedenzuella. Essas duas espécies e Ateleia glazioveana, outra planta que causa fibrose cardíaca, continuam sendo importantes no Sul e Sudeste do Brasil. Outras espécies menos importantes e que ocasionamente provocam surtos acidentais de intoxicação são as plantas que contém glicosídeos cardiotóxicos, tais como Nerium oleander e Kalanchoe blossfeldiana. Recentemente, várias metodologias experimentais foram empregadas para evitar intoxicações por plantas que contêm monofluoroacetato de sódio. Estas metodologias incluem a indução de aversão condicionada utilizando cloreto de lítio, a utilização de doses repetidas não tóxicas de folhas para induzir resistência, o uso de acetamida para prevenir as intoxicações e a inoculação intraruminal de bactérias degradantes de monofluoroacetato de sódio.(AU)

This review updates information about cardiotoxic plants affecting ruminants in Brazil. Currently it is known that there are at least 131 toxic plants belonging to 79 genera. Twenty five species affect the heart function. Plants that contain sodium monofluoroacetate (Palicourea spp., Psychotria hoffmannseggiana, Amorimia spp., Niedenzuella spp., Tanaecium bilabiatum and Fridericia elegans) cause numerous outbreaks of poisoning, mainly in cattle, but buffaloes, sheep and goats are occasionally affected. Poisoning by Palicourea marcgravii remains the most important due to the wide distribution of this plant in Brazil. New species of the genus Palicourea containing sodium monofluoracetate, such as Palicourea amapaensis, Palicourea longiflora, Palicourea barraensis, Palicourea macarthurorum, Palicourea nigricans, Palicourea vacillans and Palicourea aff. juruana were described in the amazon region. In the northeast region, the most important toxic plant for cattle is Amorimia septentrionalis. In the midwest, outbreaks of Niedenzuella stannea poisoning have been reported in cattle in the Araguaia region and the disease needs to be better investigated for its occurrence and importance. Tetrapterys multiglandulosa and Tetrapterys acutifolia, two plants causing cardiac fibrosis also contain sodium monofluoroacetate and were reclassified to the genus Niedenzuella. These two plants and Ateleia glazioveana, other plant that causes cardiac fibrosis continues to be important in the southeastern and south of Brazil. Other less important are the plants that contain cardiotoxic glycosides, such as Nerium oleander and Kalanchoe blossfeldiana, in wich poisonings are generally accidental. Recently, several experimental methodologies were successfully employed to avoid poisonings by sodium monofluoroacetate containing plants. These methodologies include the induction of food avertion using lithium chloride, the ministration of repeatedly non-toxic doses of leaves to induce resistance, the use of acetamide to prevent poisonings and the intraruminal inoculation of sodium monofluoroacetate degrading bacteria.(AU)

Avaliação cardíaca com cintilografia com 123 I-mlBG e ventriculografia radioisotópica em pacientes submetidos à quimioterapia com antraciclinas na infância e adolescência / Cardiac scintigraphy evaluation with 123I-mIBG and radionuclide ventriculography in patients undergoing anthracycline chemotherapy in childhood and adolescence

INTRODUÇÃO: O câncer infantil é a primeira causa de morte em crianças, nos países desenvolvidos. Nos últimos 40 anos, graças ao desenvolvimento da Oncopediatria e de drogas como as antraciclinas (ATC), a taxa de cura tem atingido até 80%. Isto repercutiu em significativo aumento da sobrevida e, consequentemente, nos efeitos deletérios da quimioterapia com ATC, como a cardiotoxicidade. A fim de estudar os efeitos tardios da quimioterapia com ATC sobre o sistema nervoso cardíaco simpático (SNS), foi realizado estudo de cintilografia com 123I-mIBG (meta-iodobenzilguanedina ligado ao iodo123) e comparado com dose dos ATCs e fração de ejeção do ventrículo esquerdo (FEVE), através da ventriculografia radioisotópica (VR). As variáveis analisadas pela cintilografia com 123I-mIBG foram a relação coração/mediastino (C/M) e a taxa de clareamento (TC) que sinalizam o funcionamento neuronal cardíaco. MÉTODOS: realizado estudo transversal de pacientes assintomáticos submetidos à quimioterapia com ATC na infância e adolescência, com período de 2 a 21 anos, após o término do tratamento, e com ecocardiograma (ECO) normal. Dos 118 pacientes participantes recrutados, 27 foram excluídos (motivos: radioterapia torácica, desistência e uso de cardioprotetores). Os dados clínicos e patológicos dos 91 pacientes participantes foram coletados dos prontuários ou através de anamnese. Simultaneamente foi estudado um grupo controle (40 voluntários), e, com as avaliações de imagens com 123I-mIBG e VR, foi preenchida uma ficha de coleta padronizada previamente elaborada e digitada em banco de dados no Software IBM® SPSS® Statistics 20.0.1 for Windows, para posterior análise. Os achados dos pacientes foram analisados e comparados aos do grupo controle. RESULTADOS: Neste grupo, a média de acúmulo da 123I-mIBG - 3,5h, avaliada pela relação C/M, foi de 2,23 com IC [95%] (2,17-2,29). A média da TC foi de 10,27% com IC [95%] (7,52-13,03). Para ambas as informações, os valores apresentaram-se...

INTRODUCTION: Child cancer is the first cause of children's death in developed countries. In the last 40 years, thanks to the development of the pediatric oncology and drugs like the Anthracyclines (ATC), cure rate has reached up to 80%. This reflected a significant improvement in survival and as a consequence the deleterious effects from chemotherapy, like cardiotoxicity, has emerged. In order to study the later effects of the chemotherapy with ATC on the sympathetic nervous system (SNS) cardiac 123I-mIBG (123Imetaiodobenzylguanidine) scintigraphy was performed and compared to the left ventricle ejection fraction (LVEF), through radionuclide ventriculography (RV). The variables analized by the 123I-mIBG scintigraphy were the heart/mediastinum ratio (H/M) and the washout rate (WR). METHODS: This is a transversal study of asymptomatic patients undergoing ATC chemotherapy in childhood and adolescence, ages varying from 2 to 21 years after the end of the treatment and normal echocardiogram (ECO). From the 118 recruted participant subjects, 27 were excluded ( thoracic radiotherapy, abandonment and use of cardioprotectors). The clinical and pathological data from the 91 patients were collected from medical records or clinical history. A control group of 40 healthy volunteers(28 male, 14 females; ages varying from 3 to 36) was studied simultaneously and evaluated as well with 123I-mIBG and RV. All data collected were stored in a databank for later analysis, patients findings versus control group. RESULTS: In the patient group the average H/M ratio from the late 123I-mIBG image was 2,23 with CI [95%] (2,17-2,29), and average WR was 10,27% with CI [95%] (7,52-13,03). The control group had the H/M ratio of 2,26 with CI [95%] (2,18-2,34) and the WR rate of 9,64% with CI [95%] (5,76-13,52). The comparison between groups was not significant. However, it has to be highlighted that 6,6% of all the patients had abnormal H/M values which were...

O papel do ecocardiograma na quimioterapia / The role of echocrdiography in chemotherapy / El Papel del ecocardiograma en la quimioterapia

Trata-se de uma revisão a respeito da importância do ecocardiograma na detecção precoce da disfunção cardíaca diastólica e/ou sistólica nos pacientes submetidos à quimioterapia, visando a evidenciação precoce das alterações anatômicas causadas por estes agentes antes do seu estabelecimento de forma irreversível. Serão abordados tanto os parâmetros clássicos na avaliação sisto-diastólica, como a definição do papel do strain bidimensional na atualidade.

Se trata de una revisión respecto a la importancia del ecocardiograma en la detección precoz de la disfunción cardíaca diastólica y/o sistólica en los pacientes sometidos a la quimioterapia, buscando la evidencia precoz de las alteraciones anatómicas causadas por estos agentes antes de su establecimiento de forma irreversible. Serán abordados tanto los parámetros clásicos en la evaluación sisto-diastólica, como la definición del papel del strain bidimensional en la actualidad

Intravenous human umbilical cord blood improves elctrophysiological and metabolic properties in ISO induced myocardial necrosis in rats.

Rats treated with isoproterenol (ISO, 85 mg/kg, sc, twice at an interval of 24 h) showed a significant increase in heart rate, mean arterial blood pressure, pressure rate index, ST elevation on ECG, and a significant increase in the levels of cardiac marker enzymes- lactate dehydrogenase, and creatine kinase in serum and a significant reduction in superoxide dismutase, and catalase and increase in thiobarbituric acid reactive substance activity in heart tissue. Treatment with Human umbilical cord blood (hUCBC; 500 and 1000 µL, iv, via the tail vein; 2 h after the second dose of ISO) significantly restored back to normal levels and showed a lesser degree of cellular infiltration and infarct size in histopathological and planimetry studies respectively. Thus, hUCBC ameliorates cardiotoxic effects of isoproterenol and may be of value in the treatment of myocardial infarction.

Efficacy of high dose of magnesium sulphate for cardiac arrhythmias in patients of wheat pill poisoning

To study the prophylactic effects of High Dose Magnesium Sulphate on Cardiac Arrhythmias, Cardiogenic shock and associated mortality in Cases of Aluminum Phosphide Poisoning. Seventy One patients of wheat pill poisoning were randomly selected. Thirty seven were given high dose of Magnesium Sulphate [study group] and 34 were given low dose of magnesium sulphate [control group] through intravenous route along with other supportive measures. Patients were observed for cardiac arrhythmias and mortality in both groups. Study end point was safe discharge from the hospital or death. The mean age of the sample was 25.27 +/- 7.48 years. Frequency of cardiac arrhythmias was 40.54%[n=15] in study group versus 55.88% [n=19] in the control group. Average length of stay and frequency of cardiogenic shock was slightly lower in the study group, i.e., 1.42 +/- 0.65 days while it was 1.78 +/- 1.38 days for the control group. Overall, mortality in both the groups was 66.20% [n=47], which remained almost equal in both groups or slightly favored study group with 64.86% [n=24] in the study and 67.65% [n=23] in the control group. High dose magnesium sulphate administration was found to be helpful for cardiac arrhythmia and shock but mortality remained unchanged

Avaliação das alterações cardiotóxicas decorrentes do uso da doxorrubicina: estudo experimental em ratos / Clinical evaluation of the doxorubicin-induced cardiotoxicity: experimental study in rats

A doxorrubicina é um dos quimioterápicos mais utilizados no tratamento de tumores sólidos e hematopoiéticos, embora possa causar reações adversas, especialmente cardiomiopatia secundßria. Apesar do potencial cardiotóxico, a doxorrubicina ainda é amplamente utilizada devido a sua alta eficßcia e baixo custo. esse trabalho objetiva-se estudar a sintomatologia associada ao uso da doxorrubicina em ratos, para elucidar seus efeitos cardiotóxicos. Dez ratos Wistar machos foram distribuidos em dois grupos: tratado, o qual recebeu 5mg/kg de doxorrubicina em 1,0mL de salina, via intraperitoneal a cada sete dias, durante quatro se- manas; e controle, o qual recebeu apenas 1,0 mL de salina nas mesmas condições descritas. Realizou-se eletrocardiograma antes dos tratamentos e após quatro semanas, juntamente com ecocardiograma. Os animais do grupo tratado apresentaram apatia, emagrecimento, desidratação e fezes diarreicas com muco, indicando disfunção metabólica decorrente da toxicidade do quimioterßpico. Em dois animais, o quadro clínico evoluiu para óbito, 19 dias após início do tratamento. No eletrocardiograma detectou-se aumento na amplitude das ondas P e R, sugerindo sobrecarga atrial e ventricular esquerda, respectivamente. A onda T apresentou amplitude superior à onda R, provavelmente devido a alterações eletrolíticas secundßrias ao quadro de desidratação e diarreia. Arritmias atriais e ventriculares, contudo, não foram detectadas. Foi diagnosticada disfunção ventricular nos animais que receberam doxorrubicina, quando avaliados por ecocardiografia de deformação miocßrdica (velocidade e deslocamento radiais do ventrículo esquerdo). Conclui-se que a doxorrubicina provoca cardiotoxicidade dose-dependente com redução progressiva da função ventricular esquerda, a qual pode ser diagnosticada precocemente com a ecocardiografia strain...

Doxorubicin is one of lhe most common drugs used in lhe treatment of solid and emopoietic tumors; however it causes a dose-dependet adverse effects, mainly cardiomyopathy. Despite the obvious cardiac toxicity potential, doxorubicin is still widely used due t0 its high efficiency and low cost. Therefore, this research aims to study the sytmptoms associated with the use of doxorubicin in rats, in order to elucidate its cardiac toxicity. Ten male Wistar rats were distributed into two groups: treated, which received 5mg/kg of doxorubicin in 1.0 mL saline intraperitoneal weekly, for four weeks, and control, which received only 1.0 mL of saline under lhe same conditions described. Electrocardiography was performed before treatment and atter four weeks when echocardiography was done as well. The treated group showed apathy, weight loss, dehydration and diarrheal stools with mucus, indicating metabolic dystunction due to the toxicity of chemotherapy. Two animals died, 19 days after lhe beginning of the experiment The electrocardiogram detected an increase in the amplitude of P. R and S waves, suggesting atrial and ventricular overload, respectively. The greater amplitude of the T-wave when compared to the R wave occurred probably due to electrolyte alterations caused by dehydration and diarrhea. Nevertheless, atrial and ventricular ar- rhythmias were not detected. Ventricular dysfunction was diagnosed in animais that received doxorubicin when evaluated by strain echocardiography (left ventricular radial velocity and displacement). It was concluded that doxorubicin causes a dose-dependent cardiotoxicity, with a progressive left ventricular dysfunction which may be early detected using the strain echocardiography...

Cardiotoxicidad por antimoniales / Antimonials cardiotoxicity

Las políticas de vigilancia epidemiológica en Colombia han hecho énfasis en el diagnóstico y el tratamiento oportuno de la leishmaniasis en cualquiera de sus formas (visceral, cutánea o mucocutánea), sin embargo, no existe control sobre las reacciones adversas que pueden presentar los pacientes medicados con los antimoniales pentavalentes, fármacos usados en el país para tratar esta enfermedad tropical. A pesar de ser medicamentos empleados durante décadas, sus mecanismos de acción no están del todo establecidos y en parte tampoco sus reacciones adversas, sin embargo, es de suma importancia prevenirlas y saber como actuar en caso de presentarse. El caso reportado muestra como reacción adversa cardiotoxicidad secundaria a tratamiento con estibogluconato de sodio en una paciente con diagnóstico de leishmaniasis cutánea, asociado a hipokalemia; en una cuidadosa comparación con casos reportados y estudios epidemiológicos se puede establecer una asociación de antimoniales y síndrome de QT largo como primer paso de la cascada letal de cardiotoxicidad.

Surveillance policies in Colombia have emphasized diagnosis and timely treatment of leishmaniasis in any of its forms (visceral, cutaneous or mucocutaneous), however there is no control on adverse reactions that may occur in patients taking pentavalent antimonials, drugs used in the country to try this tropical disease. Despite being drugs used for decades, their action mechanisms are not fully established and neither their adverse reactions, all the same, it is extremely important to prevent them and know what to do if it presents. The reported case shows as adverse reaction, secondary cardiotoxicity to sodium stibogluconate treatment in a patient with diagnosis of cutaneous leishmaniasis associated with hypokalemia, in close comparison with case reports and epidemiological studies it can be set an association of antimony and long QT syndrome as the first step of the cascade lethal cardiotoxicity.

Cardiac Toxicities Associated with Herbal Remedies

PURPOSE: Herbal preparations have long been used for medical purposes by traditional cultures, and their use is increasing in modern societies. However, many herbal agents produce specific cardiovascular toxicities in humans. We performed this study in order to investigate the clinical characteristics of the cardiac toxicities associated with herbal remedies. METHODS: We conducted a retrospective study of 45 patients (mean age 57+/-10 years) who presented with cardiotoxicity between January 2007 and May 2011 due to ingestion of herbal remedy substances. Patients were identified as suffering cardiotoxicity if they presented with chest pain, EKG abnormality, and elevation of cardiac enzyme. RESULTS: Of the 45 total cases, 17 included hemodynamic instability (37.8%), 7 with increasing cardiac enzyme (15.6%), 2 with cardiac arrest (4.4%) and one case of mortality (2.2%). The cardiotoxic herb group that demonstrated the worst clinical course was Ranunculaceae. CONCLUSIONS: In our study results, 57.6% of the herbal intoxication patients demonstrated the effects of cardiotoxicity. Thus, we recommend careful monitoring of herbal intoxication patients.

Toxicidad por anestésicos locales: revisión de la literatura / Toxicity due to local anesthetic agents: literature review

Los anestésicos locales (AL) son medicamentos muy empleados en la práctica anestésica, con baja presentación de efectos adversos y, en el caso de toxicidad, una alta mortalidad. Actualmente las tasas de toxicidad sistémica han disminuido, del 0,2 % al 0,01 %, por el uso de medidas preventivas y desarrollo de medicamentos más seguros. Dado el riesgo de mortalidad latente, los estudios en humanos no son factibles, siendo la fuente de información disponible la extrapolación de estudios animales o reportes de caso. Las manifestaciones de toxicidad severa por AL, se dan principalmente con la administración intravascular más que por la absorción tisular; siendo así la bupivacaína el AL con mayor riesgo. Clínicamente se observa alteración del estado de conciencia y convulsiones tónico-clónicas seguidas de compromiso cardiovascular, dado por bloqueos de la conducción y colapso cardiovascular de difícil manejo. En cuanto al manejo, la prevención es la base de éste seguido de una técnica anestésica adecuada; rápido reconocimiento y diagnostico e inicio temprano de medidas de rescate según el ACLS y más recientemente el uso concomitante de emulsiones lipídicas al 20 %, soportado en reportes de caso con resucitación exitosa.

Local anesthetics (LA) are drugs widely used in the practice of anesthesia, with low incidence of adverse events; however, in case of toxicity, mortality is very high. Currently, the systemictoxicity rates have dropped from 0.2 % to 0.01 %, thanks to the use of preventive measures and to the development of safer drugs. Inview of the high risk of latent mortality, studies in humans are not feasible and hence the available sources of information are extrapolated animal studies or case reports. Severe LA toxicity manifestations occur mainlyas a result of intravascular administration rather than due to tissue absorption; hence, bupivacaine is the LA that exhibits the highest risk. Clinically there are awareness disorders and tonic-clonic seizures followed by cardiovascular involvement resulting from conduction blocks and difficult to manage cardiovascular collapse. With regards to management, prevention is the key, followed by an adequate anesthetic technique; rapid identification and diagnosis and early application of ACLS rescue measures.More recently, the concomitant use of 20 % lipid emulsions has been supported by successful resuscitation case reports.

Propuesta de protocolo de biopsia cardíaca. Servicio de Anatomía Patológica y Departamento de Cardiología / Proposal of cardiac biopsy protocol. Service of Pathology and Department of Cardiology / Proposta de protocolo de biópsia cardíaca. Serviços de anatomia patológica e departamento de cardiologia

Introducción: Las biopsias endomiocárdicas se utilizan habitualmente para el diagnóstico de muchas patologías que han sido agrupadas por Billigham y Tazelaar en inflamatorias, metabólicas, endocrinas, neuromusculares, tóxicas, procesos linfoproliferativos y el diagnóstico de rechazo a trasplante cardíaco para evaluar la cardiotoxicidad por drogas (antraciclinas, dexoxirubina, cocaína, alcohol, entre otras); también como análisis de miocardio isquémico y su zona limítrofe. Objetivo: Trataremos de evaluar desde un punto de vista cuantitativo, la amplitud de observaciones que se han hecho de la biopsia cardíaca, en un innumerable listado de patologías, desde la MO a la ME (Microscopía óptica a microscopía electrónica). Se intentará graduar los hallazgos morfológicos de la misma, enlazándolos con la topografía y función, teniendo en cuenta, además, los factores bioquímicos y genéticos, organismos vivos, drogas, agentes físicos y procedimientos diagnósticos. Material y Métodos: Para el presente estudio se realizó una recopilación bibliográfica teniendo en cuenta los siguientes criterios: 1) cambios morfológicos sub-celulares-matriz tisular; 2) score de necrosis; 3) score inflamatorio, 4) score de fibrosis; 5) depósitos intracelulares y de pigmentos. Procesamiento de las muestran fijadas en formol buffer (tiempo 2-12 hs.) con coloración de rutina: H/E, Pas, Masson, Zihel Neelsen prolongada, Perls, Azul de Toluidina, Rojo Congo, Orceina. Panel con técnicas de I.H.Q.(BIO SB®).Conclusión: Creemos importante establecer un método que permita hacer una adecuada correlación clínico patológica aplicable a mejorar la interpretación de la injuria tisular, celular y facilitar de este modo, una correcta elección terapéutica.

Introdução: As biópsias endomiocárdicas são utilizadas habitualmente para o diagnóstico de muitas patologias, que foram agrupadas por Billigham e Tazelaar em inflamatórias, metabólicas, endócrinas, neuromusculares, tóxicas, processos linfoproliferativos e o diagnóstico de rejeição a trasplante cardíaco, para avaliar a cardiotoxicidade por drogas (antraciclinas, doxorrubicina, cocaína, álcool, entre outras). Também como análise de miocárdio isquêmico e sua zona limítrofe. Objetivo: Trataremos de avaliar sob o ponto de vista quantitativo, a amplidão de observações feitas da biópsia cardíaca, em uma inumerável lista de patologias, de MO a ME.Tentaremos graduar os descobrimentos morfológicos da mesma, enlaçando-os com a topografia e função, levando em consideração também os fatores bioquímicos e genéticos, organismos vivos, drogas, agentes físicos, procedimentos e diagnósticos.Material e Métodos: para o presente estudo realizou-se uma recopilação bibliográfica considerando os seguintes critérios, 1) alterações morfológicas subcelulares-matriz tissular; 2) escore de necrose; 3) escore inflamatório, 4) escore de fibrose; 5) depósitos intracelulares e de pigmentos. Processamento das amostras fixadas em formol buffer (tempo 2 -12 h.) com coloração de rotina: H/E, Pas, Masson, Zihel Neelsen prolongada, Perls, Azul de Toluidina, Vermelho Congo, Orceína. Painel com técnicas de I.H.Q. (BIO SB®). Conclusão: Achamos importante estabelecer um método que permita fazer uma adequada correlação clínico patológica aplicável a melhorar a interpretação da injúria tisular celular e, deste modo, facilitar uma correta decisão terapêutica.

Introduction: The endomiocárdica biopsies is habitually used for the diagnosis of many pathologies, grouped by Billigham and Tazelaar in inflammatory, metabolic, endocrine, neuromuscular, toxic, processes linfoproliferative and in diagnosis of rejection to heart transplant or to evaluate the cardiotoxicity for drugs (antracicline, dexoxirubine, cocaine, alcohol among other). Also as analysis of cardiac ischemia and their bordering area. Objective: We will try to evaluate from a quantitative point of view, the width of observations that you/they have been made of the heart biopsy in a countless listing of pathologies, from the MO to ME. We will try to graduate the morphologic discoveries of the same one, connecting them with the topography and function, also keeping in mind the biochemical and genetic factors, alive organisms, you drug, physical agents, procedures diagnoses. (Sherman Bloom, pag 329, I Diagnose of Cardiovasc. Pathology).Material and Methods: for the present study was carried out a bibliographical summary keeping in mind the following approaches, 1) changes morphologic subcellular-main tissue; 2) necrosis score; 3) inflammatory score 4) fibrosis score; 5) deposits intracellular and of pigments. Prosecution of they show them fixed in formol buffer (time 2 -12 hs.) with routine coloration: H/E, Pas, Masson, Zihel lingering Neelsen, Perls, Blue of Toluidine, Red Congo, Orceine. Panel with technical of I.H.Q. (BIO SB®). Conclusion: We believe as very important to establish a methodology eich allow an applicable pathological clinical appropriate correlation to improve the interpretation of the tissue insult and to facilitate in this way a correct therapeutic election.

Biochemical and toxinological characterization of Naja sumatrana (Equatorial spitting cobra) venom

The lethal and enzymatic activities of venom from Naja sumatrana (Equatorial spitting cobra) were determined and compared to venoms from three other Southeast Asian cobras (Naja sputatrix, Naja siamensis and Naja kaouthia). All four venoms exhibited the common characteristic enzymatic activities of Asiatic cobra venoms: low protease, phosphodiesterase, alkaline phosphomonoesterase and L-amino acid oxidase activities, moderately high acetylcholinesterase and hyaluronidase activities and high phospholipase A2. Fractionation of N. sumatrana venom by Resource® S cation exchange chromatography (GE Healthcare, USA) yielded nine major protein peaks, with all except the acidic protein peak being lethal to mice. Most of the protein peaks exhibit enzymatic activities, and L-amino acid oxidase, alkaline phosphomonoesterase, acetylcholinesterase, 5'-nucleotidase and hyaluronidase exist in multiple forms. Comparison of the Resource® S chromatograms of the four cobra venoms clearly indicates that the protein composition of N. sumatrana venom is distinct from venoms of the other two spitting cobras, N. sputatrix (Javan spitting cobra) and N. siamensis (Indochinese spitting cobra). The results support the revised systematics of the Asiatic cobra based on multivariate analysis of morphological characters. The three spitting cobra venoms exhibit two common features: the presence of basic, potentially pharmacologically active phospholipases A2 and a high content of polypeptide cardiotoxin, suggesting that the pathophysiological actions of the three spitting cobra venoms may be similar.(AU)

Value of cardiac troponin I measurement in prediction of anthracycline-induced cardiotoxicity in breast cancer patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the value of cardiac troponin I (CTnI) measurement in predicting anthracycline-induced cardiotoxicity in patients with breast cancer.</p><p><b>METHODS</b>This study was conducted among 186 breast cancer patients receiving anthracycline-based chemotherapy. Serum cTnI concentrations before and after each cycle of the chemotherapy and the left ventricular ejection fraction (LVEF) before and at the 2nd, 4th and 6th months of the treatment were recorded. According to serum cTnI concentration, the patients were divided into CTnI+ group (with serum CTnI concentration of no less than 0.1 ng/ml, n=60) and CTnI- (<0.1 ng/ml) group (n=126).</p><p><b>RESULTS</b>No patients in this series experienced cardiac heart failure (CHF). The number of patients with a LVEF reduction by over 10% from the baseline was 16 (26.7%) in CTnI+ group, as compared to 7 (5.6%) in CTnI- group, showing a significant difference between the two groups (P<0.01).</p><p><b>CONCLUSION</b>CTnI can be a useful marker for early prediction of anthracycline-induced cardiotoxicity in patients with breast cancer.</p>

Imipramine induced ECG changes in rabbits

An uncontrolled In-vivo study was conducted to assess alterations in heart rate, QT interval and QRS complex duration in male chinchilla rabbits. Animals [n=10] were treated with 25mg/5ml/day imipramine, through oral route of administration for five days. The electrocardiographic tracings were recorded by needle electrodes in all conscious animals first before and then after drug administration, following every day up to five days. It showed cardiotoxic effects like QT interval prolongation in addition to significant widening of QRS complex, along with decrease in heart rate. Because of these cardiotoxic effects prescribing imipramine to patients with prominent cardiovascular risk factors desires added attentiveness

Cardiotoxicidade e quimioterapia / Cardiotoxicity and chemotherapy

JUSTIFICATIVA E OBJETIVOS: Muitos esquemas de quimioterapia são relacionados a efeitos cardiotóxicos, particularmente no seguimento em longo prazo. A avaliação cardiológica é necessária, mas o treinamento específico neste campo em particular é escasso. O objetivo deste estudo foi apresentar os mecanismos de ação e efeitos adversos, principalmente cardíacos, de diferentes fármacos usados frequentemente em oncologia. CONTEÚDO: Recomendações gerais para prevenção, diagnóstico precoce e estratégias terapêuticas serão discutidas. CONCLUSÃO: Pesquisas adicionais são necessárias para desenvolver novas estratégias de prevenção e tratamento das principais complicações.

Dosagem de marcadores cardíacos CK-MB e TnIc e eletrólitos no envenenamento experimental por veneno de sapo em cães / Determination of cardiac markers and CK-MB TnIc and electrolyte in experimental poisoning by poison frog in dogs

Dentre os sinais sistêmicos causados pelo envenenamento por veneno de sapo (bufotoxina) em cães, os efeitos cardiotóxicos são um dos mais importantes. O objetivo deste estudo foi avaliar as potenciais alterações no músculo cardíaco de cães envenenados experimentalmente por veneno de sapo e observar as alterações eletrolíticas que podem ocorrer nesse tipo de envenenamento. Utilizaram-se 20 cães divididos em grupo controle (n=5) e grupo envenenado (n=15). O veneno de sapo foi extraído por meio de compressão manual das glândulas paratóides. Após anestesia geral, os cães do grupo controle receberam placebo (solução fisiológica) e os do grupo envenenado uma alíquota do veneno por sonda orogástrica. As colheitas de sangue para dosagem dos marcadores cardíacos foram realizadas seis e 24 horas após o envenenamento. As colheitas de sangue para dosagem dos eletrólitos foram realizadas antes e duas, quatro, seis e 12 horas após o envenenamento. A análise estatística empregada foi o teste não-paramétrico de Mann-Withney (P<0,05). Os cães envenenados por veneno de sapo apresentaram elevação dos níveis dos marcadores cardíacos CK-MB e TnIc, confirmando a cardiotoxicidade do veneno. Hipocalemia e hipocalcemia foram também observadas nos cães envenenados.

Among the systemic signs of toad venom (bufotoxin) poisoning in dogs, the cardiotoxic effects are one of the most important. Thus, the objective of this experiment was to evaluate potential changes in the cardiac muscle in dogs poisoned experimentally by toad venom and to observe the eletrolyte alterations which may occur in this condition. Twenty dogs divided into control group (n=5) and poisoned group (n=15) were utilized. The toad venom was extracted by manual compression of the paratoidic glands. After general anesthesia, dogs in the control group received placebo and dogs in the poisoned group received the venom by orogastric catheter. Samples for dosage were collected 6 hours and 24 hours after poisoning and 0, 2, 4, 6 and 12 hours after poisoning for electrolytes dosage. The Man-Withney test was used for statistical analysis (P<0.05). The poisoned dogs showed (saline) elevated levels of cardiac markers CK-MB and TnIc, confirming the cardiotoxic effect of the bufotoxin. Hypokalemia and hypocalcemia were also observed.