Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function.

Background—: Previous studies suggested that transplantation of autologous bone marrow–derived mononuclear cells (BMNCs) improves heart function in chronic chagasic cardiomyopathy. We report the results of the first randomized trial of BMNC therapy in chronic chagasic cardiomyopathy. Methods and Results—: Patients 18 to 75 years of age with chronic chagasic cardiomyopathy, New York Heart Association class II to IV heart failure, left ventricular ejection fraction (LVEF) <35, and optimized therapy were randomized to intracoronary injection of autologous BMNCs or placebo. The primary end point was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5. Between July 2005 and October 2009, 234 patients were enrolled. Two patients abandoned the study and 49 were excluded because of protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had a trimmed mean age of 52.4 years (range, 50.8–54.0 years) and LVEF of 26.1 (range, 25.1–27.1) at baseline. Median number of injected BMNCs was 2.20×10 ⁸ (range, 1.40–3.50×10 ⁸ ). Change in LVEF did not differ significantly between treatment groups: trimmed mean change in LVEF at 6 months, 3.0 (1.3–4.8) for BMNCs and 2.5 (0.6–4.5) for placebo ( P =0.519); change in LVEF at 12 months, 3.5 (1.5–5.5) for BMNCs and 3.7 (1.5–6.0) for placebo ( P =0.850). Left ventricular systolic and diastolic volumes, New York Heart Association functional class, Minnesota quality-of-life questionnaire, brain natriuretic peptide concentrations, and 6-minute walking test did also not differ between groups. Conclusion—: Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with chronic chagasic cardiomyopathy. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00349271.

Background: Posttransplant cell tracking, via stem cell labeling, is a crucial strategy for monitoring and maximizing benefits of cell-based therapies. The structures and functionalities of polysaccharides, proteins, and lipids allow their utilization in nanotechnology systems. Materials and methods: In the present study, we analyzed the potential benefit of curcumin-loaded nanoparticles (NPC) using Vero cells (in vitro) and NPC-labeled adipose-derived mesenchymal stem cells (NPC-ADMSCs) (in vivo) in myocardial infarction and sciatic nerve crush preclinical models. Thereafter, transplantation, histological examination, real time imaging, and assessment of tissue regeneration were done. Results: Transplanted NPC-ADMSCs were clearly identified and revealed potential benefit when used in cell tracking. Conclusion: This approach may have broad applications in modeling labeled transplanted cells and in developing improved stem cell therapeutic strategies.

Objective To quantify the trend of ischaemic heart disease (IHD) deaths in Brazil during the last decade (2000–2010) for various population characteristics and to forecast the upcoming mortality trends across regions in Brazil until the year 2015. Design Nationwide comparative observational study. Patients and methods The population studied encompassed all adult residents (≥20 years) living in five Brazilian regions between 2000 and 2010. Demographic, economic and mortality data were obtained from Brazilian National Mortality Data System and National Applied Economics Research Institute. Subnotified deaths were redistributed proportionally to IHD deaths. Age-standardised mortality rates (ASMRs) per 100 000 inhabitants, by sex and region, were calculated employing a standard Brazilian population and constructing multivariate regression models to quantify and to project temporal trends. Main outcome measures Absolute numbers of death due to IHD and region-specific death rates in Brazil by age and sex. Results During the study period, 627 786 men and 452 690 women died due to IHD in Brazil. ASMR trends across all regions for men and women converged, driven by a declining trend in the South and Southeast and an opposite incline in the North and Northeast (p<0.05). Future projections demonstrated potential widening of the observed North–South gap in coming years. Conclusions The IHD death trend in Brazil has changed from a decline to a stagnant state. However, a significant discrepancy in mortality trends exists between the northern and southern regions, which is likely to widen further. Reappraisal of the public health policies tailored to populations with diverse socioeconomic structures is urgently required.

Degeneration of cardiac tissues is considered a major cause of mortality in the western world and is expected to be a greater problem in the forthcoming decades. Cardiac damage is associated with dysfunction and irreversible loss of cardiomyocytes. Stem cell therapy for ischemic heart failure is very promising approach in cardiovascular medicine. Initial trials have indicated the ability of cardiomyocytes to regenerate after myocardial injury. These preliminary trials aim to translate cardiac regeneration strategies into clinical practice. In spite of advances, current therapeutic strategies to ischemic heart failure remain very limited. Moreover, major obstacles still need to be solved before stem cell therapy can be fully applied. This review addresses the current state of research and experimental data regarding embryonic stem cells (ESCs), myoblast transplantation, histological and functional analysis of transplantation of co-cultured myoblasts and mesenchymal stem cells, as well as comparison between mononuclear and mesenchymal stem cells in a model of myocardium infarction. We also discuss how research with stem cell transplantation could translate to improvement of cardiac function.

The consequences and risks of prolonged physical exercise are not well established. To evaluate the effects of prolonged physical exercise on the participants of a 24-hour ultramarathon race. Twenty male runners were selected for evaluation a day before and immediately after the race, where the athletes had to cover the most distance in 24 hours. Clinical, laboratory and echocardiographic data were obtained at both evaluations. Mean distance covered was 140.3 ± 18.7 km. Runners showed weight loss (p < 0.001) and decrease in systolic (p < 0.001) and diastolic (p = 0.004) blood pressure. Hematological changes were compatible with the physiological stress. Plasma levels of creatine phosphokinase strikingly increased post-race (163.4 ± 56.8 vs. 2978.4 ± 1921.9 U/L; p < 0.001) and was inversely correlated with distance covered: those who covered the longest distances showed the lowest CPK levels (Pearson r = 0.69, p = 0.02). After the race, 2 runners showed a slight increase in Troponin levels. One of them also had simultaneous decrease in left ventricular ejection fraction (coronary artery disease was subsequently ruled out). Basal echocardiography assessment had shown LV hypertrophy in one and increased left atrial volume in five runners. After the race, there was a decrease in E/A ratio (p < 0.01). Prolonged physical exercise is associated with metabolic and cardiovascular alterations. Cardiac abnormalities found in our study suggest that cardiac fatigue may occur in this specific race modality. The long-term effect of these alterations, while maintaining the routine practice of prolonged strenuous physical activity, is still unknown.