Continuous Intravenous Inotropes in Ward Units: Expanding Therapy Outside Intensive Care using a Safety-Oriented Protocol / Inotrópicos Intravenosos Contínuos em Unidades de Enfermaria: Expandindo o Tratamento Além da Unidade de Terapia Intensiva Utilizando um Protocolo Orientado em Segurança

Abstract Selected clinically stable patients with heart failure (HF) who require prolonged intravenous inotropic therapy may benefit from its continuity out of the intensive care unit (ICU). We aimed to report on the initial experience and safety of a structured protocol for inotropic therapy in non-intensive care units in 28 consecutive patients hospitalized with HF that were discharged from ICU. The utilization of low to moderate inotropic doses oriented by a safety-focused process of care may reconfigure their role as a transition therapy while awaiting definitive advanced therapies and enable early ICU discharge.

Resumo Pacientes selecionados com insuficiência cardíaca (IC), clinicamente estáveis que necessitam de terapia inotrópica intravenosa prolongada podem se beneficiar de sua continuidade fora da unidade de terapia intensiva (UTI). Nosso objetivo foi relatar a experiência inicial e a segurança de um protocolo estruturado para terapia inotrópica em unidades de terapia não-intensiva em 28 pacientes consecutivos hospitalizados com IC que receberam alta da UTI. A utilização de doses inotrópicas baixas a moderadas, orientadas por um processo de cuidado focado na segurança, pode reconfigurar seu papel como terapia de transição enquanto aguarda terapias avançadas definitivas e permite a alta precoce da UTI.

Cardioprotection of Rosuvastatin Pre-conditioning on Myocardial Ischemia / Reperfusion Injury in a Rat Model

Abstract This study aimed to investigate the cardioprotection of rosuvastatin pre-conditioning (R-Pre) in a rat model of myocardial ischemia / reperfusion (I/R). Male SD rats were assigned into three groups: sham group, I/R group and R-Pre group. Rats in I/R group and R-Pre group received ischemia for 30 min and reperfusion for 2 h. In R-Pre group, rats received intragastrical administration with rosuvastatin at 5 mg/kg once daily for 1 week. After 2-h reperfusion, the cardiac function was detected by ultrasonography; the blood was collected for biochemical analysis; the heart was collected for the TUNEL staining and immunohistochemistry for Bcl-2 and Bax. Our results showed rosuvastatin pre-conditioning for 1 week could significantly reduce the infarct ratio and improve the cardiac function after myocardial I/R injury, in which attenuation of oxidative stress and cell apoptosis played an important role. Our study provides evidence on the cardioprotection of rosuvastatin pre-conditioning and highlight the use of rosuvastatin before cardiopulmonary bypass.

Anestesia en el paciente séptico / Anesthesia for the septic patient

INTRODUCTION: Sepsis corresponds to a dysregulated host response to infection that occurs with some degree of organic dysfunction. OBJECTIVE: To conduct a narrative review of the literature about the anesthetic management of the septic patient. METHODS: A structured search of the literature was carried out in the following databases: EBSCO, Pubmed, Embase, SciELO and Cochrane Library, with the terms: Anesthesia AND sepsis; anesthesia AND sepsis AND management; sepsis AND treatment; both English and Spanish. RESULTS: About 45 articles were found with important information for the development of the present review. CONCLUSIONS: The type of anesthesia, as well as the inducers and medications involved in the maintenance of general anesthesia should be chosen according to the particular condition of each patient and the experience of the anesthesiologist. Resuscitation goals, as well as protective ventilation maneuvers, should be continued or implemented during the surgery.

ANTECEDENTES: La sepsis corresponde a una respuesta disregulada del huésped a la infección que cursa con algún grado de disfunción orgánica. Frecuentemente, el paciente séptico requiere anestesia general para control del foco. OBJETIVO: Realizar una revisión narrativa de la literatura acerca del manejo anestésico del paciente séptico. MÉTODOS: Se realizó una búsqueda estructurada de la literatura en las siguientes las bases de datos: EBSCO, Pubmed, Embase, SciELO y Cochrane Library, con los términos: Anesthesia AND sepsis; anesthesia AND sepsis AND management; sepsis AND treatment; en inglés y con sus equivalentes DeCS en español. RESULTADOS: Se encontraron alrededor de 45 artículos con información importante para el desarrollo de la presente revisión. CONCLUSIONES: El tipo de anestesia, así como los inductores y medicamentos involucrados en el mantenimiento de la anestesia general deben escogerse de acuerdo a la condición particular de cada paciente y a la experiencia del anestesiólogo. Las metas de reanimación, así como las maniobras de ventilación protectora deben continuarse o implementarse en el transoperatorio

Dexmedetomidina genera óxido nítrico mediante un mecanismo independiente de la óxido nítrico sintasa inducible / Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO dependent mechanism

El infarto del miocardio es una de las principales causas de muerte a nivel mundial y se produce a consecuencia de procesos de isquemia-reperfusión (IR). El daño miocárdico generado por IR puede ser atenuado a través del pre-condicionamiento isquémico (PI) temprano, mediado por la vía RISK o PI tardío, que se asocia a una respuesta genómica en la que se activan proteínas como óxido nítrico sintasa inducible (iNOS). Las vías de señalización que median el PI también pueden ser activadas farmacológicamente. Dexmedetomi-dina (Dex) es un agonista alfa2-adrenérgico, que se ha descrito como un potente agente cardioprotector frente a IR. Recientemente, nuestro grupo describió que Dex requiere el endotelio y la activación de la vía óxido nítrico sintasa endotelial (eNOS)-óxido nítrico (NO) para pre-condicionar el miocardio. Sin embargo, no existen estudios que muestren la posible participación de iNOS en la protección conferida por Dex. La presente adenda tiene por objetivo evaluar si Dex activa iNOS en el corazón y en cardiomiocitos. Para esto, corazones de rata adulta fueron estimulados con Dex 10 nM y se observó que el fármaco aumentó la producción de NO medida por cuantificación de nitritos, mas no estimuló la activación de iNOS medida por Western blot. Además, Dex tampoco indujo el aumento de mRNA de iNOS en cardiomiocitos adultos. Por lo tanto, Dex genera NO independiente a iNOS durante su efecto pre-condicionante agudo. Sin embargo, se requieren más estudios que clarifiquen su papel en una posible protección a largo plazo frente a IR generada por Dex.

Myocardial infarction is one of the leading causes of death worldwide and is generated as a consequence of ischemia-reperfusion (IR). Myocardial damage inflicted by IR can be attenuate by early ische-mic pre-conditioning (IP), which is mediated by the RISK pathway or late IP, which is associated to a genomic response involving the activation of proteins such as inducible nitric oxide synthase (iNOS). The signaling pathways mediating IP can also be pharmacologically activated. Dexmedetomidine (Dex) is an alpha2-adrenergic receptor agonist, which has been described as a strong cardio protective agent against IR. Recently, our group reported that Dex requires the endothelium and the activation of the endothelial nitric oxide synthase (eNOS)-ni-tric oxide (NO) pathway to precondition the myocardium. However, there are no studies showing the involvement of iNOS in the protection elicited by Dex. The aim of this Addendum is to evaluate if Dex activates iNOS in the heart and cardiomyocytes. To test this, adult rat hearts were stimulated with Dex 10 nM and we observed that NO production measured by quantification of nitrites was increased, but Dex did not activate iNOS measured by Western blot. Moreover, Dex did not induce an increase in the mRNA levels of iNOS in adult cardiomyocytes. Therefore, Dex generates NO independent of iNOS during its early pre-conditioning effect. Nevertheless, more studies are required to clarify its role in a possible long term protection against IR generated by Dex.

Co-administration of Apelin and T4 Protects Inotropic and Chronotropic Changes Occurring in Hypothyroid Rats / Coadministração de Apelina e T4 tem Efeito Protetor nas Alterações Inotrópicas e Cronotrópicas que Ocorrem em Ratos Hipotireoideos

AbstractBackground:One of the most important thyroid hormone targets is the cardiovascular system. Hemodynamic changes, such as decreased resting heart rate (HR), myocardial contractility, and cardiac output, and increased diastolic pressure and systemic vascular resistance, have been observed in hypothyroid patients. Moreover, in these patients, ECG changes include sinus bradycardia and low voltage complexes (P waves or QRS complexes).Objective:This study aimed at evaluating the prophylactic effect of apelin on HR changes and QRS voltage that occur in propylthiouracil (PTU)-induced hypothyroid rats.Method:In this study, 48 adult male Wistar rats weighing 170-235g were randomly divided into 6 groups: Control group (normal saline ip injection + tap water gavage); P group (PTU 0.05%, in drinking water); A group (apelin 200 µg.kg-1.day-1, ip); PA group [co-administration of PTU and apelin]; PT group [co-administration of PTU + T4 (0.2 mg/g per day, gavage)]; and PAT group (co-administration of PTU, apelin and T4). All experiments were performed for 28 consecutive days, and then the animals were anesthetized with an ip injection of ketamine (80 mg/kg) and xylazine (12 mg/kg). Lead II electrocardiogram was recorded to calculate HR and QRS voltage.Results:Heart rate and QRS voltage increased more significantly in the hypothyroid group that consumed both apelin and T4 (201 ± 4 beat/min, 0.71 ± 0.02 mv vs. hypothyroid 145 ± 9 beat/min, 0.563 ± 0.015 mv; respectively).Conclusion:The co-administration of apelin and T4 showed a protective effect on QRS voltage and HR in PTU‑induced hypothyroid rats.

ResumoFundamento:O sistema cardiovascular é um dos alvos mais importantes dos hormônios tireoidianos. As seguintes alterações hemodinâmicas foram observadas em pacientes com hipotireoidismo: redução da frequência cardíaca (FC) de repouso, da contratilidade miocárdica e do débito cardíaco; e aumento da pressão diastólica e da resistência vascular sistêmica. Além disso, tais pacientes apresentam alterações eletrocardiográficas, como bradicardia sinusal e baixa voltagem dos complexos (ondas P e complexos QRS).Objetivo:Avaliar o efeito profilático da apelina nas alterações de FC e voltagem de QRS que ocorrem em ratos com hipotireoidismo induzido por propiltiouracil (PTU).Método:Este estudo dividiu de maneira aleatória 48 ratos Wistar machos adultos, pesando 170-235g, em seis grupos: grupo controle (CO), injeção intraperitoneal (ip) de solução salina + água potável gavagem; grupo hipotireoideo (P), PTU 0,05% em água potável; grupo A, apelina ip (200 µg.kg-1.dia-1); grupo PA, coadministração de PTU e apelina; grupo PT, coadministração de PTU e T4, 0.2 mg/g por dia por gavagem; e grupo PAT, coadministração de PTU, apelina e T4. Todos os experimentos foram realizados durante 28 dias consecutivos, sendo então os animais anestesiados com injeção ip de cetamina (80 mg/kg) e xilazina (12 mg/kg). Utilizou-se o registro do ECG na derivação DII para calcular a FC e a voltagem do QRS.Resultados:Houve aumento mais significativo da FC e da voltagem do QRS no grupo hipotireoideo que recebeu apelina e T4 (201±4 bpm, 0,71±0,02mV) do que no hipotireoideo (145±9 bpm, 0,563±0,015 mV), respectivamente.Conclusão:A coadministração de apelina e T4 mostrou efeito protetor na voltagem do QRS e FC em ratos com hipotireoidismo induzido por PTU.

Myocardial protection with prophylactic oral metoprolol during coronary artery bypass grafting surgery: evaluation by troponin I / Proteção cardíaca com uso profilático de betabloqueador oral em cirurgia de revascularização miocárdica: avaliação pela troponina I

INTRODUCTION: Biochemical markers of myocardial injury are frequently altered after cardiac surgery. So far there is no evidence whether oral beta-blockers may reduce myocardial injury after coronary artery bypass grafting. OBJECTIVE: To determine if oral administration of prophylactic metoprolol reduces the release of cardiac troponin I in isolated coronary artery bypass grafting, not complicated by new Q waves. METHODS: A prospective randomized study, including 68 patients, divided in 2 groups: Group A (n=33, control) and B (n=35, beta-blockers). In group B, metoprolol tartrate was administered 200 mg/day. The myocardial injury was assessed by troponin I with 1 hour and 12 hours after coronary artery bypass grafting. RESULTS: No significant difference between groups regarding pre-surgical, surgical, complication in intensive care (15% versus 14%, P=0.92) and the total number of hospital events (21% versus 14%, P=0.45) was observed. The median value of troponin I with 12 hours in the study population was 3.3 ng/ml and was lower in group B than in group A (2.5 ng/ml versus 3.7 ng/ml, P<0,05). In the multivariate analysis, the variables that have shown to be independent predictors of troponin I release after 12 hours were: no beta-blockers administration and number of vessels treated. CONCLUSION: The results of this study in uncomplicated coronary artery bypass grafting, comparing the postoperative release of troponin I at 12 hours between the control group and who used oral prophylactic metoprolol for at least 72 hours, allow to conclude that there was less myocardial injury in the betablocker group, giving some degree of myocardial protection.

INTRODUÇÃO: Os marcadores bioquímicos de lesão miocárdica estão frequentemente alterados após cirurgia cardíaca. Até o momento não existem evidências de que o betabloqueador oral possa reduzir a lesão miocárdica após cirurgia de revascularização miocárdica. OBJETIVO: Determinar se a administração oral profilática de metoprolol reduz a liberação de troponina cardíaca I na cirurgia de revascularização miocárdica isolada não complicada por novas ondas Q. MÉTODOS: Estudo prospectivo, randomizado, incluindo 68 pacientes divididos em 2 grupos: Grupo A (n=33, controle) e B (n=35, betabloqueador). No grupo B, o tartarato de metoprolol foi administrado na dose de 200 mg/dia. A lesão miocárdica foi avaliada pela troponina I com 1 hora e 12 horas após a cirurgia de revascularização miocárdica. RESULTADOS: Não foi observada diferença significativa entre os grupos quanto às variáveis pré-cirúrgicas, cirúrgicas, incidência de complicações na terapia intensiva (15% versus 14%; P=0,92) e o número total de eventos hospitalares (21% versus 14%; P=0,45). O valor da mediana da troponina I com 12 horas na população estudada foi de 3,3 ng/ml e foi menor no grupo B do que no grupo A (2,5 ng/ml versus 3,7 ng/ml; P<0,05). Na análise multivariada, as variáveis que demonstraram serem preditoras independentes da liberação de troponina cardíaca I com 12 horas foram: não uso de betabloqueadores e número de vasos tratados. CONCLUSÃO: Os resultados desta investigação na cirurgia de revascularização miocárdica isolada, não complicada, comparando a liberação pós-operatória de troponina cardíaca I com 12 horas entre os grupos controle e o que usou metoprolol oral profilático por pelo menos 72 horas, permitem concluir que houve menor lesão miocárdica no grupo betabloqueador, conferindo algum grau de proteção miocárdica.

Use of dopamine infusion improved oxygenation in a patient of Ebstein's anomaly with atrial septal defect.

We present the successful perioperative management of an adult patient with Ebstein's anomaly for abdominal rectopexy surgery. The patient developed mild hypotension and a fall in peripheral oxygen saturation (SpO 2 ) after administration of a graded epidural block. Correction of the fall in the blood pressure; however, did not improve the SpO 2 . The patient was administered an intravenous infusion of dopamine to improve the cardiac output and this led to improvement in the SpO 2 .

Increased cardiac endothelin-1 and nitric oxide in adriamycin-induced acute cardiotoxicity: Protective effect of Ginkgo biloba extract.

Cardiotoxicity and congestive heart failure are the major factors that limit the use of anti-neoplastic drug adriamycin (ADR). There is increasing experimental evidence that endothelin-1 (ET-1) and nitric oxide (NO) are vasoactive mediators that regulate cardiac performance. The present study was undertaken to investigate the role of ET-1 and NO in ADR-induced acute cardiotoxicity and to evaluate the protective effect of Ginkgo biloba extract (EGb761) in rats. A single dose of ADR (20 mg/kg i.p.) caused a significant increase in the cardiac enzyme activities of aspartate transaminases (AST), lactate dehydrogenase (LDH) and creatine phosphokinase isoenzyme (CK-MB) in the serum of animals. This was accompanied by significant increase in cardiac malondialdehyde (MDA), total antioxidant capacity (TAC), tumor necrosis factor-alpha (TNF-α), ET-1 and nitrite/nitrate (NOx) levels. On the other hand, reduced glutathione (GSH) was significantly depressed. Histopathological examination of heart tissues showed hyalinization of the myocardium, with interstitial edema and inflammatory exudates. Pre-treatment of the animals with EGb761 (100 mg/kg, orally) 10 days before and 5 days after ADR treatment reversed the cardiac enzyme levels to normal value, decreased cardiac MDA, TAC, TNF-α, ET-1 and NOx, increased GSH and reversed the histopathological damage induced by ADR. In conclusion, the cardioprotective effects of EGb761 on markers of ADR-induced acute cardiotoxicity appeared to have been mediated by the regulation of inflammatory and vasoactive mediators, as well as the inhibition of membrane lipid peroxidation. Thus, EGb761 may find use as promising adjuvant therapy to ameliorate cardiotoxicity of ADR.

Variações interindividuais na farmacocinética clínica de cardiotônicos / Interindividual changes in cardiotonic clinical pharmacokinetics

A insuficiência cardíaca (IC) é uma síndrome clínica complexa cujo tratamento farmacológico consiste no uso de fármacos inibidores da ECA, BRA, betabloqueadores, diuréticos e antagonistas da aldosterona. Dentre os fármacos com atividade inotrópica, para uso na IC em fase crônica, o fármaco de eleição é a digoxina; já na IC descompensada são utilizados a dobutamina e a milrinona. A farmacocinética é a ciência que estuda a absorção, distribuição, biotransformação e excreção de fármacos; quando inserida na prática clínica, apresenta como hipótese fundamental a relação que existe entre os efeitos farmacológicos do fármaco e sua concentração no sangue ou no plasma. O estabelecimento de esquemas terapêuticos racionais de fármacos é feito apartir de seus parâmetros farmacocinéticos como biodisponibilidade, volume de distribuição, clearance e tempo de meia-vida, que podem ser modificados por inúmeros fatores. Neste estudo revisou-se a farmacocinética da digoxina, dobutamina e milrinona,avaliando-se as alterações de seus parâmetros farmacocinéticos em função de fatores como idade, sexo, presença de IC e interações medicamentosas. Este conhecimento aplicado aos diferentes grupos de indivíduos contribuirá para a racionalização da terapia, aproximando-se de um esquema terapêutico individualizado.

Heart failure (HF) is a complex clinical syndrome whose pharmacological treatment includes the useof ACE inhibitors, ARBs, beta blockers, diuretics and aldosterone antagonists. Among drugs with inotropic activity, the drug of choice for use in chronic phase HF is digoxin, while dobutamine and milrinone are used for decompensated HF. Pharmacokinetics is the science studying the absorption, distribution,biotransformation and excretion of drugs. When inserted into clinical practice, its fundamental hypothesis is the relationship between the pharmacological effects of a drug and its concentration in the blood or plasma. The establishment of rational drug regimens is achieved through their pharmacokinetic parameters, such asbioavailability, distribution volume, clearance rate and half-life, which can be modified by count less factors. This study reviews the pharmacokinetics of digoxin, dobutamine and milrinone, assessing changes in their pharmacokinetic parameters that depend on factors such as age, gender, presence of HF and drug interactions. Applied to different groups of individuals, this knowledge will contribute to the rationalization of treatment, moving towards individualized regimens.

Abordagem contemporânea do choque cardiogênico / Contemporary approach of cardiogenic shock

As doenças cardiovasculares são responsáveis por 34% de todas as causas de morte no Brasil. De acordo com o Ministério da Saúde, foram registrados 500 mil casos de infarto agudo do miocárdio em 1998, com 56 mil óbitos (1). A incidência de choque cardiogênico não sofreu alterações significativas nas últimas três décadas. Ocorre em 5% a 15% dos pacientes com IAM e constitui a principal causa de morte na fase de tratamento hospitalar dos pacientes com infarto agudo do miocárdio

Cardiovascular diseases are responsible for 34% of all causes of deaths in Brazil. According to Department of Health, five hundred thousand of acute myocardial infarction cases in 1998 were registered, resulting in fifty-six thousand deaths related to the disease. The incidence of cardiogenic shock has not meaningful changing in the last three decades. It happens in 5% to 15% with IAM and it's the main cause of deaths with acute myocardial infarction in hospitalar treatment stage

Hypertensive effects of the iv administration of picomoles of ouabain

Ouabain, an endogenous digitalis compound, has been detected in nanomolar concentrations in the plasma of several mammals and is associated with the development of hypertension. In addition, plasma ouabain is increased in several hypertension models, and the acute or chronic administration of ouabain increases blood pressure in rodents. These results suggest a possible association between ouabain and the genesis or development and maintenance of arterial hypertension. One explanation for this association is that ouabain binds to the α-subunit of the Na+ pump, inhibiting its activity. Inhibition of this pump increases intracellular Na+, which reduces the activity of the sarcolemmal Na+/Ca2+ exchanger and thereby reduces Ca2+ extrusion. Consequently, intracellular Ca2+ increases and is taken up by the sarcoplasmic reticulum, which, upon activation, releases more calcium and increases the vascular smooth muscle tone. In fact, acute treatment with ouabain enhances the vascular reactivity to vasopressor agents, increases the release of norepinephrine from the perivascular adrenergic nerve endings and promotes increases in the activity of endothelial angiotensin-converting enzyme and the local synthesis of angiotensin II in the tail vascular bed. Additionally, the hypertension induced by ouabain has been associated with central mechanisms that increase sympathetic tone, subsequent to the activation of the cerebral renin-angiotensin system. Thus, the association with peripheral mechanisms and central mechanisms, mainly involving the renin-angiotensin system, may contribute to the acute effects of ouabain-induced elevation of arterial blood pressure.

Infarto perioperatorio en cirugía no-cardíaca y dexmedetomidina / Perioperative myocardical infaction in non-cardiac surgery and dexmedetomidine

La patología cardiovascular es la primera causa de muerte en Chile y en el mundo. Desde el punto de vista quirúrgico, anestesiólogos y cirujanos enfrentan más frecuentemente pacientes mayores con patología cardiovascular. La incidencia de isquemia miocárdica en pacientes de alto riesgo, sometidos a cirugía no-cardíaca, es cercana al 40 por ciento durante el perioperatorio. La incidencia de infarto miocárdico y muerte en cirugía no-cardíaca, oscila entre 1 y 5 por ciento. Existe una estrecha relación entre los eventos isquémicos perioperatorios y el aumento de la morbimortalidad cardiovascular. Por este motivo, se han desarrollado medidas terapéuticas orientadas a disminuir la incidencia de isquemia perioperatoria y aminorar el daño asociado a ella. La adecuada identificación de pacientes de riesgo, la optimización del tratamiento médico de patologías asociadas y el uso de fármacos cardioprotectores durante el perioperatorio, han mostrado disminuir la incidencia de complicaciones cardíacas. Dexmedetomidina es un agonista beta2-adrenérgico de uso frecuente en anestesia. La evidencia sugiere que posee propiedades cardioprotectoras que podrían beneficiar a pacientes quirúrgicos de alto riesgo cardiovascular. La cardioprotección conferida por dexmedetomidina estaría mediada por la modulación del sistema nervioso autónomo. La disminución de la frecuencia cardíaca y de la presión arterial observada durante su uso, evitarían el desbalance entre aporte y demanda de oxígeno miocárdico y atenuarían el estrés sobre placas ateromatosas inestables. Hasta este momento se desconoce si dexmedetomidina produce precondicionamiento cardíaco y si activa vías transduccionales asociadas a cardioprotección. Frente a la actual realidad epidemiológica en Chile y el mundo, es importante estudiar y definir, cuales son los fármacos de uso frecuente en anestesia con capacidad cardloprotectora y los mecanismos Involucrados en esta protección. Sería Interesante lograr...

Cardiovascular disease is the leading cause of death In Chile and worldwide. Anesthesiologists and surgeons often face more elderly surgical patients with cardiovascular disease. The incidence of myocardial Ischemia in patents at high risk, undergoing non-cardiac surgery is about 40 percent during the perioperative period. The incidence of myocardial Infarction and death in non-cardiac surgery is between 1 and 5 percent. There is a close relationship between perioperative Ischemic events and increased cardiovascular morbidity and mortality Therefore, therapeutic approaches have been developed to reduce the Incidence of perioperative Ischemia and lessen the damage associated with it. The proper Identification of patients at risk, optimizing the medical treatment of associated diseases and the use of cardioprotective drugs during the perioperative period have shown to decrease the Incidence of cardiac complications. The beta2-adrenergic agonist dexmedetomidine is commonly used in anesthesia. The evidence suggests that possesses cardioprotective properties that could benefit surgical patients at high cardiovascular risk. The cardioprotection conferred by dexmedetomidine would be mediated by modulation of the autonomic nervous system. The decrease in heart rate and blood pressure observed during its use could avoid the Imbalance between supply and myocardial oxygen demand and lessen the stress on unstable athermanous plaques. So far it is unknown whether dexmedetomidine produces cardiac preconditioning by activating cardioprotective-signaling pathways. Faced with the current worldwide epidemiologic situation, It would be Important to study the cardioprotective capacity of drugs frequently used in anesthesia and the mechanisms Involved In that protection. It would be interesting to achieve that definition regarding the perioperative use of dexmedetomidine.

Ecocardiograma sob estresse com dobutamina em pacientes assintomáticos com regurgitação aórtica / Ecocardiografía bajo estrés con dobutamina en pacientes asintomáticos con regurgitación aórtica / Dobutamine-stress echocardiography in asymptomatic patients with aortic regurgitation

FUNDAMENTO: A reserva contrátil diminuída pode já estar presente em pacientes portadores de regurgitação aórtica, assintomáticos com fração de ejeção (FE) normal, indicando a necessidade de avaliações frequentes e acuradas da função ventricular esquerda para detectar disfunção sistólica incipiente. OBJETIVO: Analisar se incrementos na FE em doses baixas de dobutamina podem predizer cirugia e/ou morte em pacientes com regurgitação aórtica. MÉTODOS: Eco de estresse com dobutamina foi realizado em 24 pacientes portadores de regurgitação aórtica para verificar se incrementos da FE em doses baixas de dobutamina seriam capazes de predizer a necessidade de cirurgia e/ou morte nesse grupo de pacientes. RESULTADOS: A idade média foi de 37,8±16,8 anos, e 16 (66 por cento) eram homens. A FE aumentou de um valor basal médio de 62,3±7,9 por cento para 71,5±10,5 por cento, na dose de 20 µg/kg/min de dobutamina (p < 0,001). Os pacientes foram acompanhados por 36,6±20,1 meses: dois pacientes morreram (um de morte cardiovascular) e cinco foram submetidos à cirurgia cardíaca. A FE basal se correlacionou com cirurgia e morte no seguimento de pacientes. CONCLUSÃO: A FE basal se correlacionou com cirurgia ou morte no seguimento de pacientes jovens com regurgitação aórtica. Porém, o incremento percentual na FE com dose baixa de dobutamina não foi capaz de predizer eventos nesses pacientes.

BACKGROUND: Decreased contractile reserve may already be present in asymptomatic patients with aortic regurgitation and normal ejection fraction (EF), thus indicating the need for frequent and accurate assessments of the left ventricular function for the early detection of systolic dysfunction. OBJECTIVE: To analyze if increments in EF with low dose dobutamine could predict surgery and/or death in patients with aortic regurgitation. METHDOS: Dobutamine-stress echocardiography was performed in 24 patients with aortic regurgitation in order to analyze whether EF increments at low dobutamine doses could predict the need for surgery and/or death in this group of patients. RESULTS: Mean age was 37.8±16.8 years and 16 patients (66 percent) were male. EF increased from a mean baseline value of 62.3±7.9 percent to 71.5±10.5 percent at a dobutamine dose of 20 µg/kg/min (p<0.001). The patients were followed-up for 36.6±20.1 months; two patients died (one of cardiovascular death) and five underwent cardiac surgery. Baseline EF was correlated with surgery and death in the follow-up of patients. CONCLUSION: Baseline EF was correlated with surgery or death in the follow-up of young patients with aortic regurgitation. However, the percentage increase in EF at low dobutamine doses did not allow us to predict events in these patients.

FUNDAMENTO: La reserva contráctil disminuida puede ya estar presente en pacientes portadores de regurgitación aórtica, asintomáticos con fracción de eyección (FE) normal, indicando la necesidad de evaluaciones frecuentes y cuidadosas de la función ventricular izquierda para detectar disfunción sistólica incipiente. OBJETIVO: Analizar se incrementos en la FE en dosis bajas de dobutamina pueden predecir cirugía y/o muerte en pacientes con regurgitación aórtica. MÉTODOS: Eco de estrés con dobutamina se realizó en 24 pacientes portadores de regurgitación aórtica para verificar se incrementos de la FE en dosis bajas de dobutamina serían capaces de predecir la necesidad de cirugía y/o muerte en ese grupo de pacientes. RESULTADOS: La edad promedio fue de 37,8±16,8, y 16 (66 por ciento) eran varones. La FE aumentó de un valor basal promedio de 62,3±7,9 por ciento para 71,5±10,5 por ciento, en la dosis de 20 µg/kg/min de dobutamina (p < 0,001). Los pacientes se siguieron por 36,6±20,1 meses: dos pacientes murieron (uno de muerte cardiovascular) y cinco se sometieron a cirugía cardiaca. La FE basal se correlacionó con cirugía y muerte en el seguimiento de pacientes. CONCLUSIÓN: La fe basal se correlacionó con cirugía o muerte en el seguimiento de pacientes jóvenes con regurgitación aórtica. Sin embargo, el incremento porcentual en la FE con dosis baja de dobutamina no fue capaz de predecir eventos en esos pacientes.

Levosimendán, un nuevo agente inotrópico: experiencia en niños con fallo cardíaco agudo / Levosimendan, a new inotropic drug: experience in children with acute heart failure

Introducción. El síndrome de bajo gasto cardíaco ocurre frecuentemente en el posoperatorio de pacientes con cirugía cardíaca. Las catecolaminas, utilizadas como inotrópicos, pueden provocar efectos adversos potencialmente deletéreos. El levosimendán es un nuevo fármaco inotrópico no adrenérgico con posibles beneficios en esta poblaciónde pacientes. Este estudio evaluó la seguridad y eficacia del levosimendán en niños con bajo gasto posoperatorio.Población, material y métodos. Estudio prospectivo, abierto, no controlado, realizado en la Unidad de Recuperación Cardiovascular de un hospital pediátrico de alta complejidad. Se administrólevosimendán, como uso compasivo, a todos los pacientes con bajo gasto posoperatorio refractario al tratamiento convencional. Se administró una dosisde carga de 6 μg/kg EV, seguido de 0,1 μg/kg/min por 24 h. La variable primaria predeterminada fue el impacto clínico del levosimendán sobre el gastocardíaco. Dos observadores independientes realizaron la evaluación clínica del gasto cardíaco. Se analizó la función cardíaca por ecocardiografía yvariables clínicas, bioquímicas y hemodinámicas antes de la infusión y después de ella. Resultados. Se administró levosimendán a 14 pacientesen 18 oportunidades La mediana de edadfue de 27,5 meses (r: 0,16-197) y el peso de 11,1 kg (r: 2,98-48). En 9/18 intervenciones (50%; p= 0,004) seobservó una mejoría en el gasto cardiaco. El puntaje de inotrópicos disminuyó (12,1 contra 6,1; p= 0,01),la SvO2 mejoró (69,5 ± 11,4% contra 76 ± 9,29%, p= 0,03) y la A-VDO2 disminuyó (26,78 ± 11,5% contra 20,81 ± 7,72%, p= 0,029). No se identificaron efectos adversos. Cuatro pacientes fallecieron, ninguno en relación con la administración del fármaco. Conclusiones. En el 50% de las intervenciones se observó mejoría en el gasto cardíaco. No se detectaron efectos adversos atribuibles al fármaco.

Introduction. Low cardiac output syndrome occurs frequently in pediatric patients after cardiac surgery. Catecholamines are used as inotropic drugs to treat this threatening condition, but may cause undesirable and potentially harmfull side effects. Thisstudy was performed to evaluate the efficacy and safety of levosimendan (LEVO) in pediatric patients with low cardiac output syndrome. Patients and methods. Open prospective, cuasi experimental, cohort. LEVO was given as compassionate treatment in patients with refractory possurgical low cardiac output syndrome. Every patient received an IV infusion of LEVO at 6 μg/kg during a fifteen minutes period, followed by a 24 h IV infusion at 0.1 μg/kg/min. Clinical improvement of cardiac output was the primary end point of the study. Two independent observers performedclinical evaluation, bidimensional echocardiogram, hemodinamic and laboratory tests were performed pre and after LEVO infusión. Results. LEVO was infused in 18 oportunities (fourteenchildren). The response was considered successful in 9/18 interventions (50%; p= 0.004). Both inotropic score (12.1 vs. 6,1, p= 0.01) and A-VDO22 (26.78 ± 11.5% vs. 20.81 ± 7.72%, p= 0.029) showed reduction, while SvO2 improved (69.5 ± 11.4% vs. 76 ± 9.29%, p= 0.03). No adverse effects were noticed.Four patients died, none of them related to LEVO administration. Conclusions. LEVO improved cardiac output in 50% of the interventions with pos-surgical LCOS and no adverse effect was observed.

Cardioprotective effect of lipistat against doxorubicin induced myocardial toxicity in albino rats.

Preventive role of lipistat against doxorubicin induced myocardial toxicity in rats has been reported. Cardiotoxicity was produced by doxorubicin administration (15 mg/kg for 2 weeks). Lipistat (350 mg/kg, orally) was administered as pretreatment for 2 weeks and then for 2 weeks alternated with doxorubicin. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), serum lipid profiles like total cholesterol, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were monitored after 3 weeks of last dose. Pretreatment with the lipistat significantly protected myocardium from the toxic effects of doxorubicin by reducing the elevated level of biomarker enzymes like LDH and CPK to the normal and serum lipids such as total cholesterol, triglyceride and LDL back to normal. Lipistat increases the decreased level of GSH, SOD and CAT and decreases the increased level of malondialdehyde in cardiac tissue. The repeated administration of doxorubicin causes cardiomyopathy associated with an antioxidant deficit and increased level of lipid profiles by interfering with fatty acid metabolism. The results support the lipid lowering and antioxidant properties of lipistat, which indicate the cardioprotective property against doxorubicin induced cardiotoxicity.

Levosimendana em pacientes com insuficiência cardíaca descompensada: eficácia em uma coorte brasileira. Resultados do estudo BELIEF / Levosimendan in decompensated heart failure patients: efficacy in a Brazilian cohort. Results of the BELIEF study

Fundamento: A levosimendana é um novo agente inodilatador que aumenta a contratilidade cardíaca pela sensibilização ao Ca(2+) e induz vasodilatação por meio da ativação dos canais KATP/BKCa. Objetivo: Estudar a eficácia e segurança da levosimendana em uma coorte brasileira portadora de insuficiência cardíaca descompensada e em pacientes resistentes a agonistas b-adrenérgicos. Métodos: O BELIEF (Brazilian Evaluation of Levosimendan Infusion Efficacy) foi um estudo aberto, prospectivo, multicêntrico e observacional realizado com 182 portadores de ICD de alto risco, todos tratados com levosimendana. O desfecho primário do estudo era alta hospitalar sem terapia inotrópica adicional (pacientes que responderam ao tratamento). Os desfechos secundários eram alterações nos parâmetros clínicos e hemodinâmicos e nos níveis de peptídeo natriurético cerebral (BNP). Resultados: A taxa de mortalidade foi de 14,8 por cento, e 139 dos 182 pacientes responderam ao tratamento. Entre os que não responderam, a taxa de mortalidade foi de 62,8 por cento. A pressão arterial sistólica foi um preditor de resposta ao tratamento. No grupo resistente aos agonistas b-adrenérgicos, 55,8 por cento responderam ao tratamento. Ao todo, 54 pacientes tiveram pelo menos um evento adverso, a maioria dos quais desapareceu espontaneamente ou após redução da dose da levosimendana. Houve uma melhora significativa na qualidade de vida entre 2 e 6 meses do acompanhamento (p < 0,0001). Conclusão: Nossos resultados indicam que a infusão de levosimendana é uma terapia alternativa de curto prazo para tratamento de pacientes com ICD. A gravidade da insuficiência cardíaca pode influenciar a resposta ao tratamento com levosimendana. São necessários estudos prospectivos com uma coorte brasileira que inclua também pacientes com doença de Chagas.

Background: Levosimendan is a new inodilatory agent that enhances cardiac contractility via Ca(2+) sensitization and induces vasodilation through the activation of KATP/BKCa. Objective: To study the efficacy and safety of levosimendan in a decompensated heart failure (DHF) Brazilian cohort, and in b-adrenergic agonist resistant patients. Methods: The Brazilian Evaluation of Levosimendan Infusion Efficacy (BELIEF) study was prospective, multicenter, observational and included 182 high-risk DHF patients, all of which received open-label levosimendan. Primary end point was hospital discharge without additional inotropic therapy (responder). Secondary end points were changes in hemodynamics, clinical parameters, and brain natriuretic peptide (BNP). Results: Mortality rate was 14.8 percent, and 139 of 182 patients were responders. In non responders it was 62.8 percent. Systolic blood pressure was a predictor of response. In b-adrenergic agonist resistant group, 55.8 percent were responders. Overall, 54 patients experienced at least one adverse event; most of them resolved either spontaneously or after levosimendan dose reduction. A significant improvement in quality of life was verified at 2-6 months of follow-up (p<0.0001). Conclusion: Our results suggest levosimendan infusion as an alternative therapy in the short term management of DHF patients. HF severity can influence the response to levosimendan treatment. Prospective studies are warranted in a Brazilian cohort including Chagas heart disease.

Uso de levosimendana em diversos quadros de insuficiência cardíaca aguda: [revisão] / Levosimendan use in several scenarios of acute heart failure: [review]

Nos países em que é comercializada, a administração precoce de levosimendana deve ser considerada em pacientes que permanecem sintomáticos e com dispnéia em repouso apesar da terapia inicial, principalmente aqueles com história de insuficiência cardíaca crônica ou em tratamento prolongado com betabloqueadores. Pacientes hipotensos ou com isquemia ativa não são os melhores candidatos para receber infusão de levosimendana e precisam, primeiro, ter esses problemas tratados.

In countries where it is available, early levosimendan infusion can be considered for patients who remain symptomatic with dyspnea at rest despite initial therapy, particularly those with a history of chronic heart failure or chronically treated with beta-blockers. Hypotensive patients or patients with active ischemia are not the best candidates for levosimendan administration and should have these problems addressed first.