Strain Magnitude Assessed at Rest and During Stress Echocardiography in Patients with Normal Coronary Flow Reserve

Abstract Background Coronary flow and myocardial contractile performance assessed by strain magnitude increase during a dobutamine stress echocardiogram (DSE). Normal coronary flow reserve (CFR) can be attained upon completion of a DSE at age-predicted maximum heart rate (HR) (HRmax = 220 - age)] or submaximal HR [(0.85) HRmax] or before completion (early CFR). Objective To ascertain the association between delta strain and HR in patients with early normal CFR. Methods This prospective study included patients whose normal CFR was obtained before the DSE was completed. Percentage of resting HR (%HRrest) = [(HRrest ÷ HRmax) 100]% and %HR CFR = [(HR at the time of CFR attainment) ÷ (HRmax) 100]% were recorded. Strain was assessed in the left ventricular region of interest, and delta strain was calculated as the difference between the measures obtained at HRrest and after the DSE was completed. Strain agreement analysis for HRrest, %HRrest, and %HR CFR was performed using the kappa coefficient. The Shapiro-Wilk test was used to assess data normality, and the Mann-Whitney test was used to compare the groups. A p-value < 0.05 was considered statistically significant. Results Strain measured -23.3% ± 4.3% at baseline and -31.1% ± 4.9% during the DSE. In delta strain > 8 absolute points, the ROC curves showed an area under the curve of 0.874 ± 0.07 for %HRrest (p = 0.001) and an area under the curve of 0.862 ± 0.07 for %HR CFR (p = 0.001). In delta strain > 8 points, %HRrest ≤ 42.6% of HRmax and %HR CFR ≤ 62.5% of HRmax showed an accuracy of 82.9% and 79.8%, respectively. Conclusion In this study, lower HRrest and HR at the time of CFR attainment had a good association with better myocardial contractile performance, according to the change in strain magnitude.

Curcuma Longa Abolishes Phenylephrine-Induced Contractions in Isolated Aortic Artery of Rats

Curcuma longa has biological effects. Its cardiovascular activities are yet to be scientifically studied. Objectives: To investigate the vasorelaxant effects of the aqueous extract of Curcuma longa (AECL). Methods: Aortic annuli of normotensive rats, with or without endothelium, were set up in a data storage system with nutrient solution in recipients, with scientifically recommended temperature, aeration and tension. Over contraction by Phenylephrine, the AECL (1, 3, 10, 30, 100, 300 and 1000 µg/mL) was incubated before and after incubation with atropine or L-name or indomethacin. An AECL concentration-response curve was also built over contractions caused by elevation of extracellular K+. Data were significant when p < 0.05, with GraphPad Prism 6.0 software resolutions. Results: The AECL induced 100% vasorelaxation also in the endothelium-free annuli. The part of the endothelium-dependent effect had EC50 = 4.32 ± 0.05 µg/mL. With inhibition of NO production, the EC50 increased to 126.50 ± 2.35 µg/mL; after inhibition of prostacyclin production, to 124.6 ± 0.05 µg/mL; and after muscarinic blockade, to 437.10 ± 0.2 µg/mL. Opening of K+ channels (relaxation of 56.98%) and VOCC blockade (relaxation of 31.56%) were evident. Conclusion: AECL induced significant vasorelaxation, being more significant in the presence of endothelium. The muscarinic pathway seems to be the main one involved in this effect, followed by the NO production and prostacyclin pathways. The activity in K+ channels by AECL was more significant than its VOCC blockade. The use of other models and tools to study action mechanisms will be important and elucidating

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.

DIGOXINA E VERAPAMIL INDUZEM HIPERTROFIA EM CARDIOMIÓCITOS DE RATOS SEDENTÁRIOS E/OU TREINADOS / DIGOXIN AND VERAPAMIL PROMOTE CARDIOMYOCYTE HYPERTROPHY IN SEDENTARY AND/OR TRAINED RATS / DIGOXINA Y VERAPAMILO INDUCEN HIPERTROFIA DE CARDIOMIOCITOS EN RATAS SEDENTARIAS Y/O ENTRENADAS

RESUMO Introdução: Cardiotônicos e bloqueadores de canais de cálcio são fármacos que alteram o Ca2+ intracelular e afetam o coração. Objetivo: Avaliar os efeitos da administração de verapamil e digoxina sobre a morfologia cardíaca de ratos submetidos ao treinamento intervalado (TAI). Métodos: Ratos Wistar machos divididos em seis grupos (N = 8): Controle, Digoxina (30,0 µg.kg-1/dia), Verapamil (5,0 mg.kg-1/dia), Treinado, Treinado+digoxina e Treinado+verapamil. O TAI foi realizado em esteira rolante (60 min/dia/60 dias) concomitantemente com a administração dos fármacos. Fragmentos do ventrículo esquerdo (VE) foram coletados para análise histológica. Resultados: A digoxina e o verapamil aumentaram a área total do VE (p < 0,002), capilares/área VE (p < 0,01) e área de cardiomiócitos (p < 2,8e-10), sendo que, nesta última variável, o verapamil promoveu efeito ainda maior que a digoxina. O TAI aumentou VE/PC (p < 4e-05), o diâmetro interno do VE (p < 2,7e-6), a área de cardiomiócitos (p < 1,8e-6) e reduziu o [Lac] (p < 2,6e-5). Houve interação entre TAI e fármacos na área total (p < 9,8e-5), capilares (p < 0,04), células/área (p < 0,004) e área de cardiomiócitos (p < 2e-16). Conclusão: A digoxina promoveu hipertrofia de cardiomiócitos e, quando associada ao TAI, potencializou a hipertrofia. O verapamil foi mais eficiente em aumentar a área de cardiomiócitos em comparação com a digoxina, porém somente de forma isolada.

ABSTRACT Introduction: Cardiotonics and calcium channel blockers are drugs that alter intracellular Ca2+ and can affect the heart. Objective: To evaluate the effects of administration of verapamil and digoxin on heart morphology of rats subjected to interval training (IT). Methods: Male Wistar rats were divided into groups (n = 8): Control, Digoxin (30.0µg.kg-1/day), Verapamil (5.0 mg.kg-1/day), Trained, Trained+digoxin and Trained+verapamil. The IT was performed on a treadmill (60 min/day/60 days) concurrently with the drugs administration. Fragments of the left ventricle (LV) were collected for histological analysis. Results: Digoxin and verapamil increased the total area of the LV (p<0.002), capillary/LV area (p<0.01) and cardiomyocytes area (p<2.8e-10), and in the latter variable, verapamil promoted even greater effect than digoxin. The IT increased LV/BW (p<4e-05), the inner diameter of the LV (p<2.7e-6), the area of cardiomyocytes (p<1.8e-6), and reduced the [Lac] (p<2.6e-5). There was interaction between IT and drugs in the total area (p<9.8e-5), capillaries (p<0.04), cell/area (p<0.004) and cardiomyocytes area (p <2.0e-16). Conclusions: Digoxin promoted cardiomyocyte hypertrophy and when associated with IT, potentiated the hypertrophy. Verapamil was more efficient in increasing the cardiomyocytes area compared with digoxin, but only when isolated.

RESUMEN Introducción: Cardiotónicos y bloqueadores de los canales de calcio son fármacos que alteran el Ca2+ intracelular y afectan al corazón. Objetivo: Evaluar los efectos de la administración de verapamilo y digoxina sobre la morfología del corazón de ratas sometidas a entrenamiento a intervalos (EI). Métodos: Ratas Wistar macho, divididas en seis grupos (N = 8): Control, Digoxina (30,0 µg.kg-1/día), Verapamilo (5,0 mg.kg-1/día), Entrenado, Entrenado+digoxina y Entrenado+verapamilo. El entrenamiento a intervalos se realizó en una cinta de correr (60 min/día/60 días), con la administración concomitante de fármacos. Se recogieron fragmentos del ventrículo izquierdo (VI) para el análisis histológico. Resultados: La digoxina y el verapamilo aumentaron el área total del VI (p < 0,002), capilares/área VI (p < 0,01) y el área de los cardiomiocitos (p < 2,8e-10) y, en esta última variable, el verapamilo promovió un efecto aún mayor que la digoxina. EI entrenamiento a intervalos aumentó VI/PC (p < 4e-05), el diámetro interior del VI (p < 2,7e-6), el área de los cardiomiocitos (p < 1,8e-6) y redujo el [Lac] (p < 2,6e-5). Hubo una interacción entre fármacos y el EI en el área total (p < 9,8e-5), capilares (p<0,04), células/área (p < 0,004) y el área de los cardiomiocitos (p < 2e-16). Conclusión: La digoxina promovió la hipertrofia de los cardiomiocitos y, cuando al asociarse con el EI, potenció la hipertrofia. El verapamilo fue más eficiente en el aumento de la zona de los cardiomiocitos en comparación con la digoxina, pero sólo de forma aislada.

Liguzinediol exerts positive inotropic effect by enhancing Ca 2+release from sarcoplasmic reticulum mediated by sarcoplasmic reticulum Ca2+ATPase / 中国药理学与毒理学杂志

OBJECTIVE To explore kinetic features and its underlying mechanism of the positive inotropic effect of liguzinediol(LZDO)in rats. METHODS ①An In vivo study was made to record the effect of LZDO 20 mg · kg-1 injected for 30 consecutive min from the left external jugular vein on pressure-volume relationships. ②Ex vivo study was used to record the antagonistic effect of LZDO on reduced contractility induced by caffeine. Caffeine and LZDO were perfused as follows:normal perfusion solution, caffeine 0.5 mmol · L-1,and then caffeine 0.5 mmol · L-1+LZDO 100 μmol · L-1. ③ Ca2+ transient from cardiomyocyte sarcoplasmic reticulum (SR) was measured to analyze the effect of LZDO on Ca2 +release blocked by thapsigargin. Thapsigargin and LZDO were perfused as follows:normal perfusion solution,thapsigargin 2 μmol · L-1,and then thapsigargin 2 μmol · L-1+LZDO 100 μmol · L-1.④The SR vesicles were prepared and the effect of LZDO(1,10 and 100μmol·L-1)on sarcoplasmic reticulum Ca2+ATPase(SERCA2a)activity was determined according to the ultramicro-Ca2+-ATP enzyme kit. RESULTS ① LZDO 20 mg · kg- 1 significantly reduced the end-systolic volume (Ves) and enhanced the end-systolic pressure (Pes),stroke volume (SV),ejection fraction (EF),cardiac output(CO),peak rate of rise of left ventricular pressure(+dp/dtmax)and stroke work(SW)(P<0.05). However,LZDO 20 mg · kg-1 did not significantly change the heart rate(HR )or the end-diastolic volume (Ved). ② Caffeine 0.5 mmol · L- 1 significantly enhanced HR,left ventricular developed pressure (LVDP ),and+dp∶dtmax at 5 min after caffeine and decreased at 30 min. However,LZDO 100μmol·L-1 restored the reduced HR,LVDP,and+dp/dtmax induced by caffeine at 30 min(P<0.05).③Thapsigargin 2μmol·L-1 significantly reduced the SR Ca2+transient from perfusion solution group(100±5)%to(51± 5)%(P<0.05) and LZDO 100 μmol · L-1 failed to restore the decreased Ca2+ transient〔(49 ± 4)%〕. Normalized Ca2+transients were reduced by thapsigargin 2μmol·L-1 and thapsigargin 2μmol·L-1+LZDO 100 μmol · L-1. ④ LZDO(10 and 100 μmol · L-1)significantly increased the activities of SERCA2a in perfusion solution group 0.98±0.10 to 1.17±0.20 and (1.43±0.09)μmol Pi·g-1·h-1,respectively(P<0.05). CONCLUSION LZDO can enhance SR Ca2+ gradient by activating the SERCA2a and might be developed to serve as a potential positive inotropic agent in clinical settings.

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.

Effect of levosimendan on pulmonary artery pressure in patients with pulmonary hypertension undergoing mitral valve replacement / 中华麻醉学杂志

Objective To investigate the effect of levosimendan on pulmonary artery pressure in patients with pulmonary hypertension undergoing mitral valve replacement.Methods Twenty-four ASA Ⅱ or Ⅲ and NY-HA class Ⅱ or Ⅲ patients,aged 35-60 yr,with mean pulmonary artery pressure (MPAP) ＞ 30 mm Hg,undergoing mitral valve replacement were randomly divided into 2 groups (n =12 each):control group (group C) and levosimendan group (group L).In group L,a loading dose of levosimendan 24 μg/kg was injected intravenously after aortic unclamping,followed by infusion of levosimendan at a rate of 0.2 μg· kg-1 · min-1 until 1 d after operation.Group C received the equal volume of normal saline.HR,MAP,MPAP,pulmonary capillary wedge pressure (PCWP),cardiac index (CI) were recorded at 5 min after induction (T0),at the end of CPB (T1) and at 1 h after operation (T2),and the pulmonary vascular resistance (PVR) and rate-pressure product (RPP) were calculated.The improvement in pulmonary hypertension was recorded.Results PCWP was significantly lower and CI higher at T1,2 in both groups,and HR was significantly higher at T1,2 and MPAP lower at T2 in group C,and MPAP and PVR were significantly lower at T1,2 in group L than at T0 (P ＜ 0.05).HR,MPAP and PVR were significantly lower and CI was significantly higher at T1,2,RPP was significantly lower at T2 and the improvement in pulmonary hypertension was higher in group L than in group C (P ＜ 0.05).Conclusion Levosimendan can improve pulmonary hypertension without increasing the myocardial oxygen consumption and with a significant increase in myocardial contractility in patients with pulmonary hypertension undergoing mitral valve replacement.

A QSAR study on a series of simplified digitalis-like compounds acting on Na+,K+-ATPase

Among the cardiotonics (agents against congestive heart failure), the most important group is of the digitalis cardiac glycosides, but since these compounds suffer from a low therapeutic index, attention has been paid to investigating safer cardiotonic agents through the inhibition of Na+,K+-ATPase, the mechanism by which the digitalis cardiac glycosides elicit their action. Recently, a series of perhydroindenes were studied for their Na+,K+-ATPase inhibition activity. We report here a QSAR study on them to investigate the physicochemical and structural properties of the molecules that govern their activity in order to rationalize the structural modification to have more potent drugs. A multiple regression analysis reveals a significant correlation between the Na+,K+-ATPase inhibition activity of the compounds and Kier’s first order valence molecular connectivity index of their R5-substituents and some indicator parameters, suggesting that the R5-substituents of the compounds containing atoms with low valence and high saturation and the R1-substituents having =N−O− moiety will be conducive to the activity.

Seguridad y eficacia de la utilización de levosimendán sin dosis de carga en una unidad de falla cardiaca especializada / Safety and effectiveness of levosimendan administration without loading dose in a specialized heart failure unit

Objetivo: evaluar la eficacia y seguridad del uso de levosimendán en pacientes con falla cardiaca severa crónica descompensada con signos evidentes de bajo gasto, e indicación de utilización de inotrópico, utilizando el medicamento sin dosis de carga, con una mayor concentración y en infusión continua hasta completar la dosis de 12.5 miligramos en total. Metodología: estudio retrospectivo, descriptivo. Se evaluaron los cambios en la presión arterial media, desarrollo de arritmias o muerte durante la infusión y clase funcional I (NYHA) antes y dos meses después de recibir el medicamento. Resultados: se observó cambio en la clase funcional durante el seguimiento a dos meses. La infusión del medicamento fue bien tolerada y no se observaron efectos adversos significativos durante la hospitalización. La presión arterial media antes de la infusión fue 71± 21.6 vs 75 ± 20.9 mmHg 24 horas después, y 71 ± 21.6 vs 71.6 ± 21.4 mmHg 48 horas después. Ningún paciente presentó arritmias inducidas por el inotrópico y se presentó solamente una muerte (4.7%) por sepsis. Conclusiones: el presente reporte es una experiencia inicial que sugiere que la administración de la infusión de levosimendan sin bolo inicial disminuye la incidencia de hipotensión y arritmias en los pacientes con falla cardiaca y puede emplearse en un servicio de hospitalización diferente a la Unidad de Cuidado Intensivo con seguridad (Acta Med Colomb 2011: 36: 68-72).

Objective: to evaluate the safety and effectiveness of levosimendan administration in patients with chronic heart failure, signs of low output, and indications for inotropic therapy. The protocol included a continuous infusion of levosimendan without loading dose, with a total dosage of 12.5 miligrams. Methods: a retrospective, descriptive study was performed to evaluate changes in mean arterial pressure, the development of arrhythmias, adverse effects like death during the infusion, and functional changes in the two months after the treatment. Results: the infusion was well tolerated, without side effects. Mean arterial pressure before the infusion was 71± 21.6 vs. 75 ± 20.9 mmHg 24 hours after and 71 ± 21.6 vs. 71.6 ± 21.4 48 hours after. There was one death (4.7%), explained by non-cardiovascular causes (sepsis). An improvement in functional class was observed during the follow-up. Conclusion: this report of an initial experience suggests that the administration of levosimendan infusion without loading dose is safe and can be used outside the intensive care unit (Acta Med Colomb 2011: 36: 68-72).

Efeitos agudos de levosimendana e dobutamina na duração do QRS em Pacientes com insuficiência cardíaca / Acute effects of levosimendan and dobutamine on QRS duration in patients with heart failure / Efectos agudos de levosimendana y dobutamina en la duración del QRS en pacientes con insuficiencia cardíaca

FUNDAMENTO: A levosimendana é um novo agente inotrópico que aumenta a contratilidade cardíaca sem aumentar a captação celular de cálcio, de forma a não causar sobrecarga de cálcio e arritmias relacionadas. Em pacientes com insuficiência cardíaca (IC), a duração prolongada do QRS está associada com um aumento no risco de mortalidade e morte súbita cardíaca. Mudanças estruturais no ventrículo esquerdo podem levar à contração assíncrona, causando atraso de condução e um QRS prolongado no ECG de superfície. OBJETIVO: O objetivo do presente estudo foi comparar os efeitos agudos de levosimendana e dobutamina na duração do QRS em pacientes com IC grave e ritmo sinusal. MÉTODOS: 60 pacientes consecutivos com IC isquêmica foram incluídos no estudo e randomizados em dois grupos para infusão de levosimendana (n=37) ou dobutamina (n=23). 67,2 por cento eram homens; a média da idade era 66,4 ± 9,2 anos para todos os pacientes. A duração basal do QRS nos grupos levosimendana e dobutamina foi 120,44 ± 23,82 ms vs 116,59 ± 13,80 ms respectivamente. A fração de ejeção do ventrículo esquerdo (FEVE) estava diminuída em ambos os grupos (23,15 ± 8,3 vs 24,56 ± 7,5 por cento). RESULTADOS: No grupo levosimendana, a duração do QRS diminuiu do valor basal para 116,47 ± 24,56 ms (p=0,006), enquanto não houve diferença significante no grupo dobutamina (p=0,605). Ambos os medicamentos causaram um aumento na FEVE, mas este foi significante apenas no grupo levosimendana (27,95 ± 8,9 por cento p=0,003 vs 26,67 ± 7,6 por cento, p=0,315). CONCLUSÃO: O estudo sugere que a administração de levosimendana, mas não de dobutamina, encurta a duração do QRS no ECG de superfície, possivelmente por causar uma contração coletiva nas fibras do músculo do ventrículo esquerdo. A base molecular desse efeito ainda precisa ser esclarecida.

BACKGROUND: Levosimendan is a novel inotropic agent that enhances cardiac contractility without increasing cellular calcium intake, so that it is not supposed to cause intracellular calcium overload and related arrhythmias. In patients with heart failure, prolonged QRS duration is associated with increased risk of mortality and sudden cardiac death. Structural changes in the left ventricle may lead to asynchronous contraction, causing conduction delay and a prolonged QRS on the surface electrocardiogram. OBJECTIVE: We aimed to compare the acute effects of levosimendan and dobutamine on QRS duration in patients with severe heart failure and sinus rhythm. METHODS: Sixty consecutive patients with ischemic heart failure were enrolled for the study and randomized into two groups for levosimendan (n=37) or dobutamine (n=23) infusions. 67.2 percent were male; mean age was 66.4±9.2 years for all patients. Baseline QRS durations in levosimendan and dobutamine groups were, 120.44 ± 23.82 ms vs 116.59 ± 13.80 ms respectively. Baseline ejection fractions were both depressed (23.15 ± 8.3 percent vs 24.56 ± 7.5 percent). RESULTS: In the levosimendan group, QRS duration shortened from baseline value to 116.47 ± 24.56 msec (p=0.006), whereas dobutamine group showed no significant change (p=0.605). Both drugs caused an increase in ejection fraction, but only the levosimendan group showed significance (27.95 ± 8.9 percent p=0.003 vs 26.67 ± 7.6 percent, p=0.315). CONCLUSION: We suggest that the administration of levosimendan, not dobutamine, shortens QRS duration on the surface ECG, possibly by means of providing collective contraction in the left ventricle muscle fibers. The molecular basis of this effect remains to be clarified.

FUNDAMENTO: La levosimendana es un nuevo agente inotrópico que aumenta la contractibilidad cardíaca sin aumentar la captación celular de calcio, de forma de no causar sobrecarga de calcio y arritmias relacionadas. En pacientes con insuficiencia cardíaca (IC), la duración prolongada del QRS está asociada a un aumento en el riesgo de mortalidad y muerte súbita cardíaca. Cambios estructurales en el ventrículo izquierdo pueden llevar a la contracción asíncrona, causando atraso de conducción y un QRS prolongado en el ECG de superficie. OBJETIVO: EL objetivo del presente estudio fue comparar los efectos agudos de levosimendana y dobutamina en la duración del QRS en pacientes con IC grave y ritmo sinusal. MÉTODOS: 60 pacientes consecutivos con IC isquémica fueron incluidos en el estudio y randomizados en dos grupos para infusión de levosimendana (n=37) o dobutamina (n=23). 67,2 por ciento eran hombres; la media de la edad era 66,4±9,2 para todos los pacientes. La duración basal del QRS en los grupos levosimendana y dobutamina fue 120,44±23,82 vs. 116,59±13,80 respectivamente. La fracción de eyección del ventrículo izquierdo (FEVI) estaba disminuida en ambos grupos (23,15±8,3 vs. 24,56±7,5). RESULTADOS: En el grupo levosimendana, la duración del QRS disminuyó del valor basal para 116,47±24,56 ms (p=0,006), en cuanto no hubo diferencia significativa en el grupo dobutamina (p=0,605). Ambos medicamentos causaron un aumento en la FEVI, pero este fue significativo apenas en el grupo levosimendana (27,95±8,9 p=0,003 vs. 26,67±7,6, p=0,315). CONCLUSIÓN: El estudio sugiere que la administración de levosimendana, pero no de dobutamina, acorta la duración del QRS en el ECG de superficie, posiblemente por causar una contracción colectiva en las fibras del músculo del ventrículo izquierdo. La base molecular de ese efecto aun precisa ser aclarada.

Digitálicos: os resultados do DIG no século XXI / Digoxin: the results of the DIG study in the XXI century / Digitálicos: los resultados del DIG en el siglo XXI

Depois da divulgação de que não houve significância estatística na mortalidade geral do estudo DIG, a indicação dos digitálicos nos esquemas de tratamento da insuficiência cardíaca congestiva (ICC) reduziu drasticamente. Estudos post hoc, que reavaliaram os dados do DIG, indicaram que um aspecto não considerado neste ensaio multicêntrico exerce influência decisiva no prognóstico dos pacientes: a concentração sérica da digoxina. Em relação àqueles que receberam placebo, a mortalidade geral e a hospitalização foram reduzidas em pacientes com concentração de digoxina inferior a 0,9 ng/ml. No primeiro trabalho que avaliou a influência dos digitálicos em modelo experimental de ICC, verificamos em nosso laboratório que ratas com síndrome congestiva secundária a infarto do miocárdio têm a sobrevida prolongada sob tratamento com digitoxina. As informações atuais recomendam que os méritos dos digitálicos continuem a ser analisados para estabelecer adequadamente sua importância no tratamento da ICC.

After the report that there was no statistical significance in the general mortality of the DIG study, the indication of digoxin in the treatment regimens for congestive heart failure (CHF) drastically decreased. Post hoc studies that reassessed the DIG study data, indicated that an aspect that was not considered in this multicenter study has a critical influence on the prognosis of patients: the serum levels of digoxin. Regarding those that received a placebo, the general mortality and hospitalization were decreased in patients with a digoxin level < 0.9 ng/ml. At the first study that assessed the influence of digitalis in an experimental model of CHF, we verified in our lab that female rats with congestive syndrome secondary to myocardial infarction have a prolonged survival when undergoing treatment with digitoxin. The current information recommends that the merits of digoxin continue to be analyzed in order to adequately establish its importance in the treatment of CHF.

Después de la divulgación de que no hubo significancia estadística en la mortalidad general del estudio DIG, la indicación de los digitálicos en los esquemas de tratamiento de la insuficiencia cardíaca congestiva (ICC) se redujo drásticamente. Estudios post hoc, que reevaluaron los datos del DIG, indicaron que un aspecto no considerado en este ensayo multicéntrico ejerce influencia decisiva en el pronóstico de los pacientes: la concentración sérica de la digoxina. En relación a aquellos que recibieron placebo, la mortalidad general y la hospitalización fueron reducidas en pacientes con concentración de digoxina inferior a 0,9 ng/ml. En el primer trabajo que evaluó la influencia de los digitálicos en modelo experimental de ICC, verificamos en nuestro laboratorio que ratas con síndrome congestivo secundario a infarto de miocardio tienen la sobrevida prolongada bajo tratamiento con digitoxina. Las informaciones actuales recomiendan que los méritos de los digitálicos continúen a ser analizados para establecer adecuadamente su importancia en el tratamiento de la ICC.

Evaluation of the myocardial protection of trimetazidine during percutaneous coronary intervention:a multi-center randomized and controlled clinical study / 中华内科杂志

Objective To evaluate the myocardial protection effects of trimetazidine during percutaneous coronary intervention (PCI). Methods 101 patients from 5 hospitals with stable or unstable angina pectoris were enrolled in this study. All the patients were randomized into two groups: a trimetazidine group (n = 54) and a control group ( n = 47). The trimetazidine group received oral trimetazidine 20 mg three times a day for (5±2 ) days before coronary angiography and a loading dose of 60 mg 30 minutes before PCI. The daily routine dosage was continued for 4 weeks after the procedure. The control group received similar treatment except trimetazidine. For each patient, the angina pectoris attacks, CK-MB,electrocardiogram and echocardiogram were noted. Results Angina did not occur in trimetazidine group during the procedure but occurred in 12 patients( 25.5% ) in the control group( P <0.001 ). The changes of ST-segment and T wave during balloon dilatation in PCI procedure were less in the trimetazidine group (60.8% vs 78.3% , P < 0.05). Ejection fraction in the trimetazidine group was higher than that in the control group 4 weeks [ ( 66.6±7.1 ) % vs ( 63.0±7.7 ) % , P = 0.03 ] after PCI. Conclusion Trimetazidine could reduce the frequency of angina pectoris attacks and myocardial damage during PCL It also improves left ventricular function during follow-up after PCL

Memantine prevents cardiomyocytes nuclear size reduction in the left ventricle of rats exposed to cold stress

OBJECTIVES: Memantine is an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist used to treat Alzheimer's disease. Previous studies have suggested that receptor blockers act as neuroprotective agents; however, no study has specifically investigated the impact that these drugs have on the heart. We sought to evaluate the effects of memantine on nuclear size reduction in cardiac cells exposed to cold stress. METHOD: We used male EPM-Wistar rats (n=40) divided into 4 groups: 1) Matched control (CON); 2) Memantine-treated rats (MEM); 3) Rats undergoing induced hypothermia (IH) and 4) Rats undergoing induced hypothermia that were also treated with memantine (IHM). Animals in the MEM and IHM groups were treated by oral gavage administration of 20 mg/kg/day memantine over an eight-day period. Animals in the IH and IHM groups were submitted to 4 hours of hypothermia in a controlled environment with a temperature of - 8ºC on the last day of the study. RESULTS: The MEM group had the largest cardiomyocyte nuclear size (151 ± 3.5 μm³ vs. CON: 142 ± 2.3 μm³; p<0.05), while the IH group had the smallest mean value of nuclear size. The nuclear size of the IHM group was preserved (125 ± 2.9 μm³) compared to the IH group (108 ± 1.7 μm³; p<0.05). CONCLUSION: Memantine prevented the nuclear size reduction of cardiomyocytes in rats exposed to cold stress.