In vivo assessment of the electrophysiological integration and arrhythmogenic risk of myocardial cell transplantation strategies.

Cell replacement strategies are promising interventions aiming to improve myocardial performance. Yet, the electrophysiological impact of these approaches has not been elucidated. We assessed the electrophysiological consequences of grafting of two candidate cell types, that is, skeletal myoblasts and human embryonic stem cell-derived cardiomyocytes (hESC-CMs). The fluorescently labeled (DiO) candidate cells were grafted into the rat's left ventricular myocardium. Two weeks later, optical mapping was performed using the Langendorff-perfused rat heart preparation. Images were obtained with appropriate filters to delineate the heart's anatomy, to identify the DiO-labeled cells, and to associate this information with the voltage-mapping data (using the voltage-sensitive dye PGH-I). Histological examination revealed the lack of gap junctions between grafted skeletal myotubes and host cardiomyocytes. In contrast, positive Cx43 immunostaining was observed between donor and host cardiomyocytes in the hESC-CMs-transplanted hearts. Optical mapping demonstrated either normal conduction (four of six) or minimal conduction slowing (two of six) at the hESC-CMs engraftment sites. In contrast, marked slowing of conduction or conduction block was seen (seven of eight) at the myoblast transplantation sites. Ventricular arrhythmias could not be induced in the hESC-CM hearts following programmed electrical stimulation but were inducible in 50% of the myoblast-engrafted hearts. In summary, a unique method for assessment of the electrophysiological impact of myocardial cell therapy is presented. Our results demonstrate the ability of hESC-CMs to functionally integrate with host tissue. In contrast, transplantation of cells that do not form gap junctions (skeletal myoblats) led to localized conduction disturbances and to the generation of a proarrhythmogenic substrate.

Role of wearable and automatic external defibrillators in improving survival in patients at risk for sudden cardiac death.

Cardiac arrest is a vexing public health problem. Fortunately, implantable cardioverter-defibrillators (ICDs) have been proven to decrease overall mortality in several populations at high risk for cardiac arrest. However, it is still unclear how to treat patients who have an elevated risk of cardiac arrest but are not in one of the identified high-risk groups proven to benefit from an ICD. It also is uncertain how to manage high-risk patients who have an accepted indication for an ICD but are unable or unwilling to have an ICD. In these clinical situations, the wearable defibrillator and automatic external defibrillator are options that should be considered. Both devices have been shown in small series to be highly effective at restoring sinus rhythm in patients with a ventricular tachyarrhythmia. However, there is still a lack of large-scale trials proving that these devices should be employed routinely in specific high-risk patient populations.

Setting and motivation in the decision to participate: An approach to the engagement of diverse samples in mobile research.

Internet and mobile based research are powerful tools in the creation of large, cohort studies (eCohort). However, recent analysis indicates that an underrepresentation of minority and low income groups in these studies might exceed that found in traditional research [1-5]. In this report, we present findings from an experiment in research engagement using the Eureka Research Platform developed to enroll diverse populations in support of biomedical clinical research. This experiment involved the recruitment of African American and Latino participants in a smartphone based survey at a temporary, charitable, dental event sponsored, in part, by the research team, in order to explore the impact of setting and approach on recruitment outcomes. 211 participants enrolled including a significant representation of African Americans (51%) and Latinos (31%) and those with education levels at high school or less (37%). Interviews conducted after the study confirmed that our recruitment efforts within the context of a service event affected the decision to participate. While further research is necessary, this experiment holds promise for the engagement of underrepresented groups in research.