Intramyocardial Injection of Autologous Bone Marrow Cells as an Adjunctive Therapy to Incomplete Myocardial Revascularization - Safety Issues

OBJECTIVES: To determine the safety of intramyocardial injection of autologous bone marrow cells in patients undergoing surgical myocardial revascularization (CABG) for severe coronary artery disease. INTRODUCTION: There is little data available regarding the safety profile of autologous bone marrow cells injected during surgical myocardial revascularization. Potential risks include arrythmias, fibrosis in the injected sites and growth of non-cardiac tissues. METHODS: Ten patients (eight men) were enrolled; they were 59&plusmn;5 years old with limiting angina and were non-optimal candidates for complete CABG. Bone marrow cells (1.3&plusmn;0.3x10(8)) were obtained prior to surgery, and the lymphomonocytic fraction (CD34+=1.8&plusmn;0.3%) was separated by density gradient centrifugation. During surgery, bone marrow cells were injected in non-grafted areas of ischemic myocardium. During the first year after surgery, the patients underwent laboratory tests, cardiac imaging, and 24-hour ECG monitoring. RESULTS: Injected segments: inferior (n=7), anterior (n=2), septal (n=1), apical (n=1), and lateral (n=1) walls. Except for a transient elevation of C-reactive protein at one month post-surgery (P=0.01), laboratory tests results were within normal ranges; neither complex arrhythmias nor structural abnormalities were detected during follow-up. There was a reduction in functional class of angina from 3.6&plusmn;0.8 (baseline) to 1.2&plusmn;0.4 (one year) (P<0.0001). Also, patients had a significant decrease in the ischemic score assessed by magnetic resonance, not only globally from 0.65&plusmn;0.14 (baseline) to 0.17&plusmn;0.05 (one year) (P=0.002), but also in the injected areas from 1.11&plusmn;0.20 (baseline) to 0.34&plusmn;0.13 (one year) (P=0.0009). CONCLUSIONS: Intramyocardial injection of bone marrow cells combined with CABG appears to be safe. Theoretical concerns with arrhythmias and/or structural abnormalities after cell therapy were not confirmed in this safety trial

Successful Improvement of Frequency and Symptoms of Premature Complexes after Oral Magnesium Administration

Background: Premature ventricular and supraventricular complexes (PVC and PsVC) are frequent and often symptomatic. The magnesium (Mg) ion plays a role in the physiology of cell membranes and cardiac rhythm. Objective: We evaluated whether the administration of Mg Pidolate (MgP) in patients with PVC and PsVC is superior to placebo (P) in improving symptoms and arrhythmia frequency. Methods: Randomized double-blind study with 60 consecutive symptomatic patients with more than 240 PVC or PsVC/h on 24-hour Holter monitoring who were selected to receive placebo or MgP. To evaluate symptom improvement, a categorical and a specific questionnaire for symptoms related to PVC and PsVC was made. Improvement in premature complex density (PCD) per hour was considered significant if percentage reduction was &gt;= 70% after treatment. The dose of MgP was 3.0 g/day for 30 days, equivalent to 260mg of Mg element. None of the patients had structural heart disease or renal failure. Results: Of the 60 patients, 33 were female (55%). Ages ranged from 16 to 70 years old. In the MgP group, 76.6% of patients had a PCD reduction &gt;70%, 10% of them &gt;50% and only 13.4% &lt;50%. In the P group, 40% showed slight improvement, &lt;30%, in the premature complexes frequency (p &lt; 0.001). Symptom improvement was achieved in 93.3% of patients in the MgP group, compared with only 16.7% in the P group (p &lt; 0.001). Conclusion: Oral Mg supplementation decreases PCD, resulting in symptom improvement. (Arq Bras Cardiol 2012;98(6):480-487

Contribuição do monitor de eventos no diagnóstico de sintomas

OBJETIVO: Avaliar o poder de contribuição do monitor de eventos sintomáticos no esclarecimento de sintomas. MÉTODOS: Foram estudados 64 pacientes encaminhados para esclarecimento de sintomas e que já haviam sido submetidos à gravação com Holter. Foram monitorizados, durante 15 dias, com gravador com memória circular com capacidade de registrar uma derivação do ECG (CM5), antes e após ativado pelo paciente. Na vigência de sintomas, o paciente acionava um comando do gravador que provocava a retenção do sinal do ECG, que era, posteriormente, transmitido a uma central via telefone. RESULTADOS: Em dois pacientes não foi possível a realização completa da monitorização, nos restantes, sintomas que motivaram a indicação do exame foram: palpitações (67,7%), tonturas (32,3%), síncopes (29%) e outros (30,6%). Em 85,5% dos pacientes houve relato de sintomas, sendo que em 62,2% houve registro de alterações eletrocardiográficas, relacionadas aos sintomas: taquicardia sinusal, 45,5%; extra-sístoles, 30,3%; taquiarritmia supraventricular, 21,2%; taquicardia ventricular, 3% e bloqueio atrioventricular, 3%. A 1ª transmissão motivada por sintoma ocorreu: 35,5% no 1º dia, 33,9% do 2° ao 5º, 12,9% do 6º ao 10º e 3,2% do 11º ao 15º. Nos pacientes onde a gravação com Holter não permitiu esclarecimento, o gravador de eventos registrou sintomas em 35,5%. CONCLUSÃO: Trata-se de método bem aceito pelos pacientes e capaz de produzir aumento significativo no esclarecimento de sintomas em relação ao Holter

Transient secondary and tertiary structure formation kinetics in the intrinsically disordered state of α-Synuclein from atomistic simulations.

In the absence of a stable fold, transient secondary structure kinetics define the native state of the prototypical and pharmacologically relevant intrinsically disordered protein (IDP) α-Synuclein (aS). Here, we investigate kinetics preventing ordering and possibly pathogenic β-sheet aggregation. Interestingly, transient β-sheets form frequently at sub μs time scales precisely at the positions observed in aS amyloid fibrils. The formation kinetics competes with rapid secondary structure dissociation rates, thus explaining the low secondary structure content. The fast secondary structure dissociation times are very similar to the dynamics of tertiary structure rearrangements. These findings suggest that the fast dissociation kinetics slows down conformational selection processes for aS aggregation, which may be a general mechanism controlling the aggregation kinetics of IDPs