Dimethyl fumarate, a small molecule drug for psoriasis, inhibits Nuclear Factor-kappaB and reduces myocardial infarct size in rats.

Persistent Nuclear Factor-kappaB (NF-kappaB) activation is hypothesized to contribute to myocardial injuries following ischemia-reperfusion. Because inhibition or control of NF-kappaB signaling in the heart probably confers cardioprotection, we determined the potency of the NF-kappaB inhibitor dimethyl fumarate (DMF) in cardiovascular cells, and determined whether administration of DMF translates into beneficial effects in an animal model of myocardial infarction. In rat heart endothelial cells (RHEC), we analysed inhibitory effects of DMF on NF-kappaB using shift assay and immunohistofluorescence. In in vivo experiments, male Sprague Dawley rats undergoing left coronary artery occlusion for 45 min received either DMF (10 mg/kg body weight) or vehicle 90 min before ischemia as well as immediately before ischemia. After 120 min of reperfusion, the hearts were stained with phthalocyanine blue dye and triphenyltetrazolium chloride. Additionally, acute hemodynamic and electrophysiologic effects of DMF were determined in dose-response experiments in isolated perfused rat hearts. DMF inhibited TNF-alpha-induced nuclear entry of NF-kappaB in RHEC. In in vivo experiments, myocardial infarct size was significantly smaller in rats that had received DMF (20.7%+/-9.7% in % of risk area; n=17) than in control rats (28.2%+/-6.2%; n=15). Dose-response experiments in isolated perfused rat hearts excluded acute hemodynamic or electrophysiologic effects as mechanisms for the effects of DMF. DMF inhibits nuclear entry of NF-kappaB in RHEC and reduces myocardial infarct size after ischemia and reperfusion in rats in vivo. There was no indication that the beneficial effects of DMF were due to acute hemodynamic or electrophysiologic influences.

Bedside quantification of atherosclerosis severity for cardiovascular risk stratification: a prospective cohort study.

OBJECTIVES: We sought to assess the ability of a new noninvasive method to quantify atherosclerosis severity and to examine its power to predict cardiovascular events. BACKGROUND: Drug prevention of cardiovascular events is effective but costly, leading to a debate about who should receive this treatment. Patient selection is often based on surrogate markers, but quantification of atherosclerosis severity is desirable. METHODS: Atherosclerosis severity was quantified by determination of specific aortic wall elastance in transthoracic echocardiography, applying the biomechanics of pulse wave propagation. After validating the method in 52 patients by measuring aortic plaque burden in transesophageal echo directly, another 336 patients were prospectively studied by monitoring atherosclerotic events at one year and comparing the results with conventional risk stratification. RESULTS: Specific aortic elastance was well correlated with plaque burden (p < 0.0001) and largely independent of confounding variables. Specific aortic elastance predicted the primary end point of "atherosclerotic death, myocardial infarction or stroke" at one year (p < 0.0002). Event rate at one year in the lowest specific elastance tertile was 1.8% (CI 0.0% to 4.3%), in the middle tertile 5.4% (CI 1.1% to 9.7%) and in the highest tertile 12.7% (CI 6.3% to 19%). Secondary end points supported these findings. Stepwise multivariate analysis identified specific aortic elastance, prior atherosclerotic events and left ventricular ejection fraction as independent risk predictors. Specific elastance was of incremental value to clinically identified variables. CONCLUSIONS: Bedside measurement of specific aortic elastance allows assessment of atherosclerosis severity. It predicts the risk for future atherosclerotic events beyond conventional risk factors, promising better targeting of pharmacologic prevention and improved cost effectiveness.

Echocardiographic quantification of atherosclerosis leads to cost-effective treatment with statins.

OBJECTIVE: Use of statins in prevention of atherosclerosis is effective but expensive. Patient selection gains wider public attention as medication costs in the US and Europe augment by 8% to 10% per year. We examined different clinical risk stratification strategies, particularly focusing on echocardiographic atherosclerosis quantification, for their impact on event reduction and cost-effectiveness in statin treatment. METHODS AND RESULTS: In a prospective, consecutive cohort of 336 patients referred to non-invasive cardiac examination, risk stratification was done by various combinations of risk factors and noninvasive atherosclerosis quantification. Atherosclerotic burden was determined through measuring "aortic elastance" by transthoracic echocardiogram, a validated non-invasive method. Cardiovascular events were recorded at a mean follow-up of one year. Echocardiographically determined atherosclerosis severity and event history, especially in combination, yielded the best selection strategies for statin treatment over a broad range of predetermined funding or required event reductions, surpassing conventional cardiovascular risk factors. From 26.8 statin-preventable events/1000 patients/year (assuming all patients treated), the best selection strategies could avoid: 24 with 66% of the cost for statin treatment (atherosclerosis and age criteria), 20.1 with <50% of the budget, 12.2 with <30% of the budget or 9.6 with <15% of the budget (using combinations of atherosclerosis and prior events), while conventional strategies without echo quantification of atherosclerosis were inferior. CONCLUSION: Non-invasive echocardiographic quantification of atherosclerosis improves efficiency and cost-effectiveness in statin treatment.

Aleitamento materno na sala de parto: a vivência da puérpera / Breastfeeding in the delivery room: the puerperal experience / Amamantamiento materno en la sala de parto: la experiencia de la puérpera

O presente trabalho é um estudo qualitativo que, utilizando como referencial teórico o Interacionismo Simbólico,teve por objetivo conhecer o significado da vivência em amamentar na sala de parto. Os dados coletados foramanalisados por meio da análise de conteúdo, modalidade temática. A questão norteadora utilizada foi: Como foipara você amamentar seu bebê logo após o nascimento, ainda na sala de parto? Os sujeitos da pesquisa forampuérperas de parto normal que amamentaram na sala de parto. As entrevistas foram gravadas e posteriormentetranscritas e categorizadas. Foram construídas seis categorias: “Vivendo um momento único”; “Reconhecendo aimportância da amamentação (com cinco subcategorias)”; “Sentindo-se tranquila em comparação comexperiências anteriores”; “Vale a pena ter parto normal”; e “Sentindo o bebê”. Este trabalho mostrou que aaceitação referida pelas mães participantes é exemplo de que colocar o bebê para mamar ainda na sala de partoé muito gratificante. Os relatos salientam que, além da possibilidade de logo sentirem seu filho como um todo, asmães mostram reconhecer o valor afetivo e nutricional desse ato, como também a importância de continuar aamamentar, vislumbrada a partir do cumprimento deste passo.

This study aimed to know the meaning of experience in nursing in the delivery room. It is a qualitative study, usingsymbolic interactionism as the theoretical framework and the collected data was analyzed using content analysis,thematic modality. The guiding question used was: How was the experience of breastfeeding your babyimmediately after birth, in the delivery room? The subjects were mothers of normal delivery who breastfed in thedelivery room. The interviews were recorded, transcribed and grouped into categories. Six categories emerged:“Living a unique moment”, “Recognizing the importance of breastfeeding (with five sub-categories)”, “Feeling calmcompared to previous experience”, “It worth having normal delivery”, and “Touching the baby”. This work showedthat the acceptance referred by the participant mothers confirms that to put the baby to suck immediately while inthe delivery room is very rewarding. The reports emphasize that, besides the possibility of bonding immediatelywith their babies, mothers recognize the affectionate and nutritional value of such action, as well as theimportance of continuing to breastfeed.

El presente trabajo es un estudio cualitativo que, utilizando como referencial teórico el Interaccionismo Simbólico,tuvo por objetivo conocer el significado de la vivencia en amamantar en la sala de parto. Los datos recogidosfueron analizados por medio del análisis de contenido, modalidad temática. La pregunta base utilizada fue:¿Cómo fue para usted amamantar su bebé en el momento siguiente del nacimiento, aun en la sala de parto? Lossujetos de la investigación fueron puérperas de parto normal que amamantaron en la sala de parto. Lasentrevistas fueron gravadas y posteriormente transcriptas y categorizadas. Fueron construidas seis categorías:“Viviendo un momento único”; “Reconociendo la importancia de la amamantamiento (con cinco subcategorías)”;“Sintiéndose tranquila en comparación con experiencias anteriores”; “Vale la pena tener parto normal”; y“Sintiendo el bebé”. Este trabajo mostró que la aceptación referida por las madres participantes es ejemplo deque colocar el bebé para mamar aun en la sala de parto es muy gratificante. Los relatos resaltan que, además dela posibilidad de sentir pronto a su hijo como un todo, las madres muestran reconocer el valor afectivo ynutricional de ese acto, como también la importancia de continuar amamantar, alumbrada a partir delcumplimiento de este paso.

Postresuscitation stunning: postfibrillatory myocardial dysfunction caused by reduced myofilament Ca2+ responsiveness after ventricular fibrillation-induced myocyte Ca2+ overload.

INTRODUCTION: Resuscitation from ventricular fibrillation (VF), particularly from prolonged VF, frequently is complicated by postfibrillatory myocardial dysfunction (postresuscitation stunning). We tested whether this dysfunction can be caused by reduced myofilament Ca2+ responsiveness after VF-induced myocyte Ca2+ overload. We also tested whether electrical defibrillation shocks contribute to this dysfunction. METHODS AND RESULTS: Myofilament Ca2+ responsiveness was estimated as ratio of left ventricular developed pressure over myocyte Ca2+ transient amplitudes (assessed as indo-1 fluorescence) in isolated perfused rat hearts before, during, and after VF (1.5 or 10 min) comparing three modes of defibrillation (biphasic electrical shocks, lidocaine, or spontaneous). We found that, independent of these defibrillation modes, myofilament Ca2+ responsiveness was significantly reduced, particularly after prolonged VF, although hearts were not ischemic or acidotic during and after VF (unchanged coronary flow, myocardial oxygen consumption, and pH of the coronary effluent). This reduction was associated with VF-induced myocyte Ca2+ overload and increasing or decreasing Ca2+ overload during VF (using 1 microM diltiazem or 6 mM extracellular calcium) led to parallel changes of myofilament Ca2+ responsiveness. However, myofilament Ca2+ responsiveness was not associated with the defibrillation shock energy (range 0.1-15.0 J/g wet heart weight). CONCLUSION: Postfibrillatory myocardial dysfunction can be caused by reduced myofilament Ca2+ responsiveness after VF-induced myocyte Ca2+ overload. Electrical defibrillation shocks (up to 15 J/g wet heart weight), however, do not significantly contribute to this dysfunction. Our findings suggest that early additional therapy targeting intracellular Ca2+ overload may normalize myocyte Ca2+ and partially prevent postresuscitation stunning.

Antiarrhythmic effect of ischemic preconditioning during low-flow ischemia. The role of bradykinin and sarcolemmal versus mitochondrial ATP-sensitive K(+) channels.

Short episodes of ischemia (ischemic preconditioning) protect the heart against ventricular arrhythmias during zero-flow ischemia and reperfusion. However, in clinics, many episodes of ischemia present a residual flow (low-flow ischemia). Here we examined whether ischemic preconditioning protects against ventricular arrhythmias during and after a low-flow ischemia and, if so, by what mechanism(s). Isolated rat hearts were subjected to 60 min of low-flow ischemia (12% residual coronary flow) followed by 60 min of reperfusion. Ischemic preconditioning was induced by two cycles of 5 min of zero-flow ischemia followed by 5 and 15 min of reperfusion, respectively. Arrhythmias were evaluated as numbers of ventricular premature beats (VPBs) as well as incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF) during low-flow ischemia and reperfusion. Ischemic preconditioning significantly reduced the number of VPBs and the incidence of VT and of VF during low-flow ischemia. This antiarrhythmic effect of preconditioning was abolished by HOE 140 (100 nM), a bradykinin B(2) receptor blocker. Similar to preconditioning, exogenous bradykinin (10 nM) reduced the number of VPBs and the incidence of VT and of VF during low-flow ischemia. Furthermore, the antiarrhythmic effects of both ischemic preconditioning and bradykinin were abolished by glibenclamide (1 microM), a non-specific blocker of ATP-sensitive K(+) (K(ATP)) channels. Finally, the antiarrhythmic effects of both ischemic preconditioning and bradykinin were abolished by HMR 1098 (10 microM), a sarcolemmal K(ATP) channel blocker but not by 5-hydroxydecanoate (100 microM), a mitochondrial K(ATP) channel blocker. In conclusion, ischemic preconditioning protects against ventricular arrhythmias induced by low-flow ischemia, and this protection involves activation of bradykinin B(2) receptors and subsequent opening of sarcolemmal but not of mitochondrial K(ATP) channels.

Rotura do seio de valsalva esquerdo com formaçäo de pseudoaneurisma subepicárdico / Rupture of the left sinus of Valsalva forming a subepicardial pseudoaneurysm

Homem de 44 anos de idade, assintomático do ponto de vista cardiovascular, apresentou ao estudo radiológico do tórax massa calcificada em mediastino médio. Durante a investigaçäo diagnóstica foi identificada, em estudo cineangiográfico, rotura do seio de Valsalva esquerdo dirigida a regiäo subepicárdica do ventrículo esquerdo com formaçäo de pseudoaneurisma de grande extensäo, produzindo acentuada distorçäo da artéria coronária esquerda e de seus ramos principais. Foi realizado tratamento cirúrgico com fechamento do orifício ao nível do seio de Valsalva esquerdo com um retalho de pericárdio bovino e esvaziamento do saco aneurismático preenchido por trombos. A evoluçäo pós-operatória foi satisfatória. O exame anátomo-patológico de fragmento da aorta näo possibilitou o diagnóstico da etiologia da rotula

A healthy 44 year-old male patient presented a calcified mass in the middle mediastinum on a chest film. During diagnostic investigation cineangiograms showed a rupture of the lep sinus of Valsalva forming a large pseudoaneurysm that produced important distortion of the left coronary artery and it’s main branches. The patient was submitted to surgical repair through the closure of the orifice of the ruptured left sinus of Valsalva with a bovine pericardium patch. The subepicardium was filled with organized thrombi which were removed. He was discharged from the hospital after uncomplicated postoperative course. Pathological examination of the aortic fragment did not yield the etiology of the rupture.